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Durvalumab and Tremelimumab With or Without High or Low-Dose Radiation Therapy in Treating Patients With Metastatic Colorectal or Non-small Cell Lung Cancer

Primary Purpose

Metastatic Colorectal Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Stage IV Colorectal Cancer AJCC v7

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Durvalumab
Radiation Therapy
Tremelimumab
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Colorectal Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed non-small cell lung cancer (cohort 1) or colorectal cancer (cohort 2)
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1.5 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • Patients in both cohorts must have progressive disease following prior therapy; specifically:

    • Cohort 1 (NSCLC): Patients must have evidence of radiologic or clinical disease progression during previous treatment with systemic PD-1 directed therapy and/or have been deemed not to derive clinical benefit from PD-1 directed treatment; this includes patients who demonstrated an initial response and subsequent progression; no prior treatment with chemotherapy or targeted agents are required; intervening therapy is allowed between previous PD-1 directed treatment and there is no required interval from prior PD-1 treatment required; PD-1 directed treatment includes treatment with antibodies targeting the PD-1 receptor such as pembrolizumab or nivolumab, as well as PD-L1 targeted antibodies such as MEDI4736 (durvalumab), atezolizumab and avelumab; these agents may have been administered as part of a clinical trial
    • Cohort 2 (colorectal cancer): Patients must have progressed on >= one-line chemotherapy
  • At least 21 days must have elapsed from prior systemic therapy (chemotherapy or radiation)
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 60%) and life expectancy greater than 6 months; furthermore, enrollment of patients with greater than 10 measurable lesions is discouraged
  • Patients must have normal organ and marrow function independent of transfusion for at least 7 days prior to screening and independent of growth factor support for at least 14 days prior to screening
  • Hemoglobin (Hgb) >= 9 g/dl
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x normal institutional limits; this will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia [predominantly unconjugated bilirubin] in the absence of evidence of hemolysis or hepatic pathology), who will be allowed in consultation with their physician
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) = < 2.5 x institutional upper limit of normal; for patients with hepatic metastases, ALT and AST =< 5 x ULT
  • Measured creatinine clearance (CL) > 40 mL/min OR calculated creatinine clearance (CL) > 40 mL/min as determined by Cockcroft-Gault (using actual body weight)
  • Patients must have at least one lesion that has not previously been irradiated (and is not within a previously radiated field) and for which palliative radiation is potentially indicated and could be safely delivered at the radiation doses specified in this protocol; this lesion must not be the only measurable lesion so that it is still possible to determine the response rate outside of the radiation treatment field; this lesion must not be within the central nervous system (CNS) (brain or spinal cord) or requiring urgent or emergent palliative radiation given the timing of radiation specified on this protocol; furthermore, this lesion:

    • For cohort 1 (NSCLC cohort) - the lesion to be irradiated must be in the lung, lymph nodes, adrenal gland or liver
    • For cohort 2 (colorectal cohort) - the lesion to be irradiated must be in the liver
  • The effects of MEDI4736 and tremelimumab on the developing human fetus are unknown; for this reason and because radiation is known to be teratogenic, evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients is required; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply:

    • Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
    • Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced oophorectomy with last menses > 1 year ago, had chemotherapy-induced menopause with > 1 year interval since last menses, or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
  • Females of childbearing potential who are sexually active with a non sterilized male partner must use at least 1 highly effective method of contraception from the time of screening and must agree to continue using such precautions for 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy; non-sterilized male partners of a female patient must use male condom plus spermicide throughout this period; cessation of birth control after this point should be discussed with a responsible physician; not engaging in sexual activity for the total duration of the drug treatment and the drug washout period is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control; female patients should also refrain from breastfeeding throughout this period
  • Non-sterilized males who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide from screening through 180 days after receipt of the final dose of durvalumab + tremelimumab combination therapy or 90 days after receipt of the final dose of durvalumab monotherapy; not engaging in sexual activity is an acceptable practice; however, occasional abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception; male patients should refrain from sperm donation throughout this period
  • Female partners (of childbearing potential) of male patients must also use a highly effective method of contraception throughout this period
  • Highly effective methods of contraception, defined as one that results in a low failure rate (ie, less than 1% per year) when used consistently and correctly are described in the table below; note that some contraception methods are not considered highly effective (e.g. male or female condom with or without spermicide; female cap, diaphragm, or sponge with or without spermicide; non-copper containing intrauterine device; progestogen-only oral hormonal contraceptive pills where inhibition of ovulation is not the primary mode of action [excluding Cerazette/desogestrel which is considered highly effective]; and triphasic combined oral contraceptive pills)

    • Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Ability of a patient or a Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document
  • Body weight > 30 kg
  • Must have a life expectancy of at least 12 weeks
  • Cohort 1 (NSCLC cohort)

    • Ability to undergo a fresh tumor biopsy for the purpose of screening for this clinical trial (including able and willing to give valid written consent) to ability or to provide an available archival tumor sample taken less than 3 months prior to study enrollment (and not obtained prior to progression on a PD-1/PD-L1 inhibitor) if a fresh tumor biopsy is not feasible with an acceptable clinical risk; tumor lesions used for fresh biopsies should be the same lesions to be irradiated when possible and should not be the same lesions used as Response Evaluation Criteria in Solid Tumors (RECIST) target lesions, unless there are no other lesions accessible; additional, optional archival tumor tissue is also requested from before the prior PD-1 directed therapy
  • Cohort 2 (colorectal cohort)

    • Ability to undergo a fresh tumor biopsy for the purpose of screening for this clinical trial (including able and willing to give valid written consent) to ability or to provide an available archival tumor sample taken less than 3 months prior to study enrollment if a fresh tumor biopsy is not feasible with an acceptable clinical risk; tumor lesions used for fresh biopsies should be the same lesions to be irradiated when possible and should not be the same lesions used as RECIST target lesions, unless there are no other lesions accessible
    • Microsatellite stable (MSS) tumor as documented by either:

      • Immunohistochemistry (IHC) testing that does not suggest loss of MLH-1, MSH-2, PMS2 or MSH6
      • Polymerase chain reaction (PCR) testing that does not suggest microsatellite instability (MSI)

Exclusion Criteria:

  • Patients who have had systemic (chemotherapy, biologic therapy or radiotherapy) within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
  • Receipt of prior radiotherapy or condition for any reason that would contribute radiation dose that would exceed tolerance of normal tissues, at the discretion of the treating physician
  • Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1)
  • Patients who are receiving any other investigational agents
  • Patients with untreated brain metastases, spinal cord compression, or leptomeningeal carcinomatosis should be excluded from this clinical trial; patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment to the brain metastases; these imaging scans should both be obtained at least four weeks apart and show no evidence of intracranial progression); in addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of =< 10 mg/day of prednisone or its equivalent (and anti-convulsants) for at least 14 days prior to the start of treatment
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to tremelimumab and MEDI4736 or previous toxicity attributed to MEDI4736 or other PD-1 or PD-L1 directed therapy that led to drug discontinuation
  • Prior exposure to immune-mediated therapy, including durvalumab and tremelimumab, except for anti-PD-1 or anti-PD-L1 therapy (including durvalumab) in NSCLC patients; this includes anti-CTLA-4 agents (prior treatment with these agents is NOT allowed in either cohort) and, excludes therapeutic anticancer vaccines, excluding therapeutic anticancer vaccines; exposure to other investigational agents may be permitted after discussion with the study principal investigator (PI)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because MEDI4736 (durvalumab), tremelimumab are immune checkpoint inhibitors with the potential for teratogenic or abortifacient effects, as is radiation therapy; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MEDI4736(durvalumab), tremelimumab and radiation, breastfeeding should be discontinued if the mother is treated with MEDI4736(durvalumab), tremelimumab and radiation
  • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab + tremelimumab combination therapy, whichever is later
  • Human immunodeficiency virus (HIV)-positive patients are ineligible; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • Any concurrent chemotherapy, immune therapy, biologic, hormonal therapy for cancer treatment
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned IP; the following are exceptions to this criterion:

    • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection)
    • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
    • Steroids as pre-medication for hypersensitivity reactions (e.g., CT scan pre-medication)
  • Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of IP; Note: local surgery of isolated lesions for palliative intent is acceptable
  • History of allogeneic organ transplantation
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis [with the exception of diverticulosis]; sarcoidosis syndrome, or other serious gastrointestinal [GI] chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves disease; rheumatoid arthritis; hypophysitis; uveitis, sarcoidosis syndrome, etc.) within the past 3 years prior to the start of treatment; the following are exceptions to this criterion:

    • Patients with vitiligo or alopecia
    • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment
    • Any chronic skin condition that does not require systemic therapy
    • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
    • Patients with celiac disease controlled by diet alone
  • History of another primary malignancy except for

    • Malignancy treated with curative intent and with no known active disease >= 5 years before the first dose of study drug and of low potential risk for recurrence
    • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    • Adequately treated carcinoma in situ without evidence of disease (e.

Sites / Locations

  • Mayo Clinic Hospital in Arizona
  • Mayo Clinic in Arizona
  • Los Angeles County-USC Medical Center
  • USC / Norris Comprehensive Cancer Center
  • University of California Davis Comprehensive Cancer Center
  • Smilow Cancer Hospital Care Center - Guilford
  • Smilow Cancer Hospital Care Center at Saint Francis
  • Smilow Cancer Center/Yale-New Haven Hospital
  • Yale University
  • Yale-New Haven Hospital North Haven Medical Center
  • Smilow Cancer Hospital Care Center-Trumbull
  • Smilow Cancer Hospital Care Center - Waterford
  • Mayo Clinic in Florida
  • Emory University Hospital Midtown
  • Emory University Hospital/Winship Cancer Institute
  • Emory Saint Joseph's Hospital
  • University of Kentucky/Markey Cancer Center
  • University of Maryland/Greenebaum Cancer Center
  • Massachusetts General Hospital Cancer Center
  • Brigham and Women's Hospital
  • Beth Israel Deaconess Medical Center
  • Dana-Farber Cancer Institute
  • Wayne State University/Karmanos Cancer Institute
  • Weisberg Cancer Treatment Center
  • Mayo Clinic in Rochester
  • Siteman Cancer Center at West County Hospital
  • Washington University School of Medicine
  • Siteman Cancer Center-South County
  • Siteman Cancer Center at Saint Peters Hospital
  • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
  • Rutgers Cancer Institute of New Jersey
  • UNC Lineberger Comprehensive Cancer Center
  • Duke University Medical Center
  • Cleveland Clinic Foundation
  • Ohio State University Comprehensive Cancer Center
  • Thomas Jefferson University Hospital
  • University of Pittsburgh Cancer Institute (UPCI)
  • Vanderbilt University/Ingram Cancer Center
  • University of Virginia Cancer Center
  • Virginia Commonwealth University/Massey Cancer Center
  • University of Wisconsin Carbone Cancer Center
  • University Health Network-Princess Margaret Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm A (tremelimumab, durvalumab)

Arm B (tremelimumab, Durvalumab, RT)

Arm C (tremelimumab, durvalumab, and RT)

Arm Description

Patients receive tremelimumab IV and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses.

Patients receive tremelimumab and durvalumab and as in Arm A. Beginning at week 2, patients receive high dose radiation therapy QD over 10 days for up to 3 fractions.

Patients receive tremelimumab and durvalumab and as in Arm A. Beginning at week 2, patients receive low dose radiation therapy every 6 hours BID on weeks 2, 6, 10 and 14.

Outcomes

Primary Outcome Measures

Overall response rate
Determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The proportion of patients with response (complete response or partial response according to RECIST) will be compared for each pair-wise comparison of radiotherapy (RT)-containing therapy and control using chi- squared tests. The difference between the proportions responding will be presented with a 90% confidence interval. For colorectal cancer, response rates within each two-stage design will be calculated and presented with 90% confidence intervals estimated using the method of Atkinson and Brown, which allows for the two-stage design.

Secondary Outcome Measures

Progression-free survival (PFS)
Distributions will be summarized using the Kaplan-Meier method. Median times for each therapy arm will be accompanied by 90% confidence intervals based on log(-log(endpoint)) methodology. For cohort 1, the pairwise comparisons between the durvalumab/tremelimumab alone and durvalumab/tremelimumab with RT arms will be conducted using log-rank tests.
Overall survival (OS)
Distributions will be summarized using the Kaplan-Meier method. Median times for each therapy arm will be accompanied by 90% confidence intervals based on log(-log(endpoint)) methodology. For cohort 1, the pairwise comparisons between the durvalumab/tremelimumab alone and durvalumab/tremelimumab with RT arms will be conducted using log-rank tests.
Objective response per immune-related response (irORR) criteria
Will be presented with 90% exact binomial confidence intervals. For cohort sizes of 30 (cohort 2) and 40 patients (cohort 1), the confidence intervals will be no wider than 0.32 and 0.28, respectively. For cohort 1, the pairwise comparisons of irORR between RT and the control arm will be conducted using chi-squared tests.
Incidence of adverse events
Assessed by Common Terminology Criteria for Adverse Events version 4.0. Safety data will be summarized for each treatment arm within each cohort. The proportions of subjects with grade-3 or higher adverse events will be presented with exact binomial confidence intervals.
Local control rate and abscopal response rates
The proportions of patients with local control within the irradiated field will be reported within each RT treatment arm and presented with 90% exact binomial confidence intervals. Similar presentations will be used for abscopal response rates. For cohort sizes of 30 (cohort 2) and 40 patients (cohort 1), the confidence intervals will be no wider than 0.32 and 0.28, respectively.
Prognostic effect of PD-L1 expression
Clinical response will be compared according to PD-L1 expression using Fisher's exact tests.
Prognostic effect of T-cell infiltration
Clinical response will be compared according to infiltration using Fisher's exact tests.

Full Information

First Posted
August 31, 2016
Last Updated
August 8, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02888743
Brief Title
Durvalumab and Tremelimumab With or Without High or Low-Dose Radiation Therapy in Treating Patients With Metastatic Colorectal or Non-small Cell Lung Cancer
Official Title
A Phase 2 Study of MEDI4736 (Durvalumab) and Tremelimumab Alone or in Combination With High or Low-Dose Radiation in Metastatic Colorectal and NSCLC
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 6, 2017 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This randomized phase II trial studies the side effects of durvalumab and tremelimumab and to see how well they work with or without high or low-dose radiation therapy in treating patients with colorectal or non-small cell lung cancer that has spread to other parts of the body (metastatic). Immunotherapy with durvalumab and tremelimumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving durvalumab and tremelimumab with radiation therapy may work better in treating patients with colorectal or non-small cell lung cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To assess safety and tolerability of combined checkpoint blockade with MEDI4736 (durvalumab) and tremelimumab alone or with high or low-dose radiation in non-small cell lung cancer (NSCLC). (NSCLC Cohort) II. To compare the overall response (excluding the irradiated lesion[s]) between combined checkpoint blockade with MEDI4736 and tremelimumab alone or combined checkpoint blockade with low or high dose radiation. (NSCLC Cohort) III. To assess safety and tolerability of combined checkpoint blockade with MEDI4736 and tremelimumab with high or low-dose radiation. (Colorectal Cohort) IV. To determine the overall response rate (excluding the irradiated lesion[s]) with combined checkpoint blockade with MEDI4736 and tremelimumab with either low or high dose radiation. (Colorectal Cohort) SECONDARY OBJECTIVES: I. To estimate median progression-free survival and overall survival. (NSCLC Cohort) II. To determine local control within the irradiated field(s) and abscopal response rates. (NSCLC Cohort) III. To evaluate associations between PD-L1 expression as well as levels of infiltrating CD3+, CD8+ T-cells and overall response. (NSCLC Cohort) IV. To explore changes in PD-L1 expression, circulating T-cell populations, T-cell infiltration, ribonucleic acid (RNA) expression, spatial relationship of immune markers, and mutational burden as a result of low or high dose radiation. (NSCLC Cohort) V. To estimate median progression-free survival and overall survival. (Colorectal Cohort) VI. To determine local control within the irradiated field and abscopal response rates. (Colorectal Cohort) VII. To evaluate associations between PD-L1 expression as well as levels of infiltrating CD3+ CD8+ T-cells and overall response. (Colorectal Cohort) VIII. To evaluate changes between PD-L1 expression as well as levels of infiltrating CD3+, CD8+ T-cells induced by targeted low or high dose radiation. (Colorectal Cohort) IX. To explore changes in circulating T-cell populations, T-cell infiltration, RNA expression, spatial relationship of immune markers, and mutational burden as a result of low or high dose radiation. (Colorectal Cohort) OUTLINE: Patients with NSCLC are randomized to Arm A, B, or C. Patients with colorectal cancer are randomized to Arm B or C. COHORT 1: Patients with NSCLC are randomized to 1 of 3 arms. ARM A: Patients receive tremelimumab intravenously (IV) and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses. ARM B: Patients receive tremelimumab and durvalumab and as in Arm A. Beginning at week 2, patients receive high dose radiation therapy once per day (QD) over 10 days for up to 3 fractions. ARM C: Patients receive tremelimumab and durvalumab and as in Arm A. Beginning at week 2, patients receive low dose radiation therapy every 6 hours twice per day (BID) on weeks 2, 6, 10 and 14. After completion of study treatment, patients are followed for up to 12 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Stage IV Colorectal Cancer AJCC v7, Stage IV Lung Non-Small Cell Cancer AJCC v7, Stage IVA Colorectal Cancer AJCC v7, Stage IVB Colorectal Cancer AJCC v7

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A (tremelimumab, durvalumab)
Arm Type
Experimental
Arm Description
Patients receive tremelimumab IV and durvalumab IV over 60 minutes every 4 weeks for up to 16 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes 4 weeks after last combination dose for up to 9 additional doses.
Arm Title
Arm B (tremelimumab, Durvalumab, RT)
Arm Type
Experimental
Arm Description
Patients receive tremelimumab and durvalumab and as in Arm A. Beginning at week 2, patients receive high dose radiation therapy QD over 10 days for up to 3 fractions.
Arm Title
Arm C (tremelimumab, durvalumab, and RT)
Arm Type
Experimental
Arm Description
Patients receive tremelimumab and durvalumab and as in Arm A. Beginning at week 2, patients receive low dose radiation therapy every 6 hours BID on weeks 2, 6, 10 and 14.
Intervention Type
Biological
Intervention Name(s)
Durvalumab
Other Intervention Name(s)
Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
Radiation Therapy
Other Intervention Name(s)
Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation
Intervention Description
Undergo radiation therapy
Intervention Type
Biological
Intervention Name(s)
Tremelimumab
Other Intervention Name(s)
Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675, CP-675,206, CP-675206, Imjudo, Ticilimumab, Tremelimumab-actl
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Overall response rate
Description
Determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The proportion of patients with response (complete response or partial response according to RECIST) will be compared for each pair-wise comparison of radiotherapy (RT)-containing therapy and control using chi- squared tests. The difference between the proportions responding will be presented with a 90% confidence interval. For colorectal cancer, response rates within each two-stage design will be calculated and presented with 90% confidence intervals estimated using the method of Atkinson and Brown, which allows for the two-stage design.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
Distributions will be summarized using the Kaplan-Meier method. Median times for each therapy arm will be accompanied by 90% confidence intervals based on log(-log(endpoint)) methodology. For cohort 1, the pairwise comparisons between the durvalumab/tremelimumab alone and durvalumab/tremelimumab with RT arms will be conducted using log-rank tests.
Time Frame
From date of randomization until objective disease progression or death, whichever occurs first, assessed up to 2 years
Title
Overall survival (OS)
Description
Distributions will be summarized using the Kaplan-Meier method. Median times for each therapy arm will be accompanied by 90% confidence intervals based on log(-log(endpoint)) methodology. For cohort 1, the pairwise comparisons between the durvalumab/tremelimumab alone and durvalumab/tremelimumab with RT arms will be conducted using log-rank tests.
Time Frame
From time of randomization to death from any cause, assessed up to 2 years
Title
Objective response per immune-related response (irORR) criteria
Description
Will be presented with 90% exact binomial confidence intervals. For cohort sizes of 30 (cohort 2) and 40 patients (cohort 1), the confidence intervals will be no wider than 0.32 and 0.28, respectively. For cohort 1, the pairwise comparisons of irORR between RT and the control arm will be conducted using chi-squared tests.
Time Frame
Up to 2 years
Title
Incidence of adverse events
Description
Assessed by Common Terminology Criteria for Adverse Events version 4.0. Safety data will be summarized for each treatment arm within each cohort. The proportions of subjects with grade-3 or higher adverse events will be presented with exact binomial confidence intervals.
Time Frame
Up to 2 years
Title
Local control rate and abscopal response rates
Description
The proportions of patients with local control within the irradiated field will be reported within each RT treatment arm and presented with 90% exact binomial confidence intervals. Similar presentations will be used for abscopal response rates. For cohort sizes of 30 (cohort 2) and 40 patients (cohort 1), the confidence intervals will be no wider than 0.32 and 0.28, respectively.
Time Frame
Up to 2 years
Title
Prognostic effect of PD-L1 expression
Description
Clinical response will be compared according to PD-L1 expression using Fisher's exact tests.
Time Frame
Up to 2 years
Title
Prognostic effect of T-cell infiltration
Description
Clinical response will be compared according to infiltration using Fisher's exact tests.
Time Frame
Up to 2 years
Other Pre-specified Outcome Measures:
Title
Patient reported symptomatic adverse events(AEs)
Description
Data will be evaluated for data quality, to characterize baseline symptom status of patients on study and the change over time, to explore the development of symptomatic AEs and the change over time, and to explore the patient scores with other relevant clinical information including, but not limited to clinician graded AEs. Feasibility of the electronic collection as well compliance of patients with the reporting will be captured.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have histologically or cytologically confirmed non-small cell lung cancer (cohort 1) or colorectal cancer (cohort 2) Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1.5 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam Patients in both cohorts must have progressive disease following prior therapy; specifically: Cohort 1 (NSCLC): Patients must have evidence of radiologic or clinical disease progression during previous treatment with systemic PD-1 directed therapy and/or have been deemed not to derive clinical benefit from PD-1 directed treatment; this includes patients who demonstrated an initial response and subsequent progression; no prior treatment with chemotherapy or targeted agents are required; intervening therapy is allowed between previous PD-1 directed treatment and there is no required interval from prior PD-1 treatment required; PD-1 directed treatment includes treatment with antibodies targeting the PD-1 receptor such as pembrolizumab or nivolumab, as well as PD-L1 targeted antibodies such as MEDI4736 (durvalumab), atezolizumab and avelumab; these agents may have been administered as part of a clinical trial Cohort 2 (colorectal cancer): Patients must have progressed on >= one-line chemotherapy At least 21 days must have elapsed from prior systemic therapy (chemotherapy or radiation) Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 60%) and life expectancy greater than 6 months; furthermore, enrollment of patients with greater than 10 measurable lesions is discouraged Patients must have normal organ and marrow function independent of transfusion for at least 7 days prior to screening and independent of growth factor support for at least 14 days prior to screening Hemoglobin (Hgb) >= 9 g/dl Absolute neutrophil count >= 1,500/mcL Platelets >= 100,000/mcL Total bilirubin =< 1.5 x normal institutional limits; this will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia [predominantly unconjugated bilirubin] in the absence of evidence of hemolysis or hepatic pathology), who will be allowed in consultation with their physician Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) = < 2.5 x institutional upper limit of normal; for patients with hepatic metastases, ALT and AST =< 5 x ULT Measured creatinine clearance (CL) > 40 mL/min OR calculated creatinine clearance (CL) > 40 mL/min as determined by Cockcroft-Gault (using actual body weight) Patients must have at least one lesion that has not previously been irradiated (and is not within a previously radiated field) and for which palliative radiation is potentially indicated and could be safely delivered at the radiation doses specified in this protocol; this lesion must not be the only measurable lesion so that it is still possible to determine the response rate outside of the radiation treatment field; this lesion must not be within the central nervous system (CNS) (brain or spinal cord) or requiring urgent or emergent palliative radiation given the timing of radiation specified on this protocol; furthermore, this lesion: For cohort 1 (NSCLC cohort) - the lesion to be irradiated must be in the lung, lymph nodes, adrenal gland or liver For cohort 2 (colorectal cohort) - the lesion to be irradiated must be in the liver The effects of MEDI4736 and tremelimumab on the developing human fetus are unknown; for this reason and because radiation is known to be teratogenic, evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients is required; women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause; the following age-specific requirements apply: Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy) Women >= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced oophorectomy with last menses > 1 year ago, had chemotherapy-induced menopause with > 1 year interval since last menses, or underwent surgical sterilization (bilateral oophorectomy or hysterectomy) Females of childbearing potential who are sexually active with a non sterilized male partner must use at least 1 highly effective method of contraception from the time of screening and must agree to continue using such precautions for 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy; non-sterilized male partners of a female patient must use male condom plus spermicide throughout this period; cessation of birth control after this point should be discussed with a responsible physician; not engaging in sexual activity for the total duration of the drug treatment and the drug washout period is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control; female patients should also refrain from breastfeeding throughout this period Non-sterilized males who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide from screening through 180 days after receipt of the final dose of durvalumab + tremelimumab combination therapy or 90 days after receipt of the final dose of durvalumab monotherapy; not engaging in sexual activity is an acceptable practice; however, occasional abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception; male patients should refrain from sperm donation throughout this period Female partners (of childbearing potential) of male patients must also use a highly effective method of contraception throughout this period Highly effective methods of contraception, defined as one that results in a low failure rate (ie, less than 1% per year) when used consistently and correctly are described in the table below; note that some contraception methods are not considered highly effective (e.g. male or female condom with or without spermicide; female cap, diaphragm, or sponge with or without spermicide; non-copper containing intrauterine device; progestogen-only oral hormonal contraceptive pills where inhibition of ovulation is not the primary mode of action [excluding Cerazette/desogestrel which is considered highly effective]; and triphasic combined oral contraceptive pills) Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately Ability of a patient or a Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document Body weight > 30 kg Must have a life expectancy of at least 12 weeks Cohort 1 (NSCLC cohort) Ability to undergo a fresh tumor biopsy for the purpose of screening for this clinical trial (including able and willing to give valid written consent) to ability or to provide an available archival tumor sample taken less than 3 months prior to study enrollment (and not obtained prior to progression on a PD-1/PD-L1 inhibitor) if a fresh tumor biopsy is not feasible with an acceptable clinical risk; tumor lesions used for fresh biopsies should be the same lesions to be irradiated when possible and should not be the same lesions used as Response Evaluation Criteria in Solid Tumors (RECIST) target lesions, unless there are no other lesions accessible; additional, optional archival tumor tissue is also requested from before the prior PD-1 directed therapy Cohort 2 (colorectal cohort) Ability to undergo a fresh tumor biopsy for the purpose of screening for this clinical trial (including able and willing to give valid written consent) to ability or to provide an available archival tumor sample taken less than 3 months prior to study enrollment if a fresh tumor biopsy is not feasible with an acceptable clinical risk; tumor lesions used for fresh biopsies should be the same lesions to be irradiated when possible and should not be the same lesions used as RECIST target lesions, unless there are no other lesions accessible Microsatellite stable (MSS) tumor as documented by either: Immunohistochemistry (IHC) testing that does not suggest loss of MLH-1, MSH-2, PMS2 or MSH6 Polymerase chain reaction (PCR) testing that does not suggest microsatellite instability (MSI) Exclusion Criteria: Patients who have had systemic (chemotherapy, biologic therapy or radiotherapy) within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study Receipt of prior radiotherapy or condition for any reason that would contribute radiation dose that would exceed tolerance of normal tissues, at the discretion of the treating physician Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) Patients who are receiving any other investigational agents Patients with untreated brain metastases, spinal cord compression, or leptomeningeal carcinomatosis should be excluded from this clinical trial; patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment to the brain metastases; these imaging scans should both be obtained at least four weeks apart and show no evidence of intracranial progression); in addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of =< 10 mg/day of prednisone or its equivalent (and anti-convulsants) for at least 14 days prior to the start of treatment History of allergic reactions attributed to compounds of similar chemical or biologic composition to tremelimumab and MEDI4736 or previous toxicity attributed to MEDI4736 or other PD-1 or PD-L1 directed therapy that led to drug discontinuation Prior exposure to immune-mediated therapy, including durvalumab and tremelimumab, except for anti-PD-1 or anti-PD-L1 therapy (including durvalumab) in NSCLC patients; this includes anti-CTLA-4 agents (prior treatment with these agents is NOT allowed in either cohort) and, excludes therapeutic anticancer vaccines, excluding therapeutic anticancer vaccines; exposure to other investigational agents may be permitted after discussion with the study principal investigator (PI) Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study because MEDI4736 (durvalumab), tremelimumab are immune checkpoint inhibitors with the potential for teratogenic or abortifacient effects, as is radiation therapy; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MEDI4736(durvalumab), tremelimumab and radiation, breastfeeding should be discontinued if the mother is treated with MEDI4736(durvalumab), tremelimumab and radiation Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab + tremelimumab combination therapy, whichever is later Human immunodeficiency virus (HIV)-positive patients are ineligible; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated Any concurrent chemotherapy, immune therapy, biologic, hormonal therapy for cancer treatment Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned IP; the following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection) Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent Steroids as pre-medication for hypersensitivity reactions (e.g., CT scan pre-medication) Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of IP; Note: local surgery of isolated lesions for palliative intent is acceptable History of allogeneic organ transplantation Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis [with the exception of diverticulosis]; sarcoidosis syndrome, or other serious gastrointestinal [GI] chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves disease; rheumatoid arthritis; hypophysitis; uveitis, sarcoidosis syndrome, etc.) within the past 3 years prior to the start of treatment; the following are exceptions to this criterion: Patients with vitiligo or alopecia Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment Any chronic skin condition that does not require systemic therapy Patients without active disease in the last 5 years may be included but only after consultation with the study physician Patients with celiac disease controlled by diet alone History of another primary malignancy except for Malignancy treated with curative intent and with no known active disease >= 5 years before the first dose of study drug and of low potential risk for recurrence Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease (e.g., cervical cancer in situ) Mean QT interval corrected for heart rate (QTc) >= 470 ms calculated from electrocardiograms (ECGs) using Fridericia's correction; abnormal ECGs should be repeated History of active primary immunodeficiency Known history of previous clinical diagnosis of tuberculosis Active infection including hepatitis B (known positive hepatitis B virus [HBV] surface antigen [HBsAg]) result or, hepatitis C; patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible; patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA); negative serologies documented over the past year are sufficient evidence of this Receipt of live, attenuated vaccine within 30 days prior to the first dose of investigational treatment; Note: patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of investigational treatment Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational treatment or interpretation of patient safety or study results Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician; patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the study physician Cohort 1 (NSCLC cohort) In regards to administration of prior anti-PD-1 or anti PD-L1 antibodies, a patients: Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy All adverse events (AEs) while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study Must not have experienced a >= grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy; NOTE: subjects with endocrine AE of =< grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day Eligibility for Food and Drug Administration (FDA)-approved agents targeting the EGFR, ROS1 or ALK pathway, which should be evaluated as per standard of care; exceptions to this requirement may be considered on a case-by-case basis by the principal investigator if the patient was previously treated with another targeted agent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan D Schoenfeld
Organizational Affiliation
Dana-Farber - Harvard Cancer Center LAO
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic Hospital in Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Los Angeles County-USC Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
USC / Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
University of California Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Smilow Cancer Hospital Care Center - Guilford
City
Guilford
State/Province
Connecticut
ZIP/Postal Code
06437
Country
United States
Facility Name
Smilow Cancer Hospital Care Center at Saint Francis
City
Hartford
State/Province
Connecticut
ZIP/Postal Code
06105
Country
United States
Facility Name
Smilow Cancer Center/Yale-New Haven Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Yale-New Haven Hospital North Haven Medical Center
City
North Haven
State/Province
Connecticut
ZIP/Postal Code
06473
Country
United States
Facility Name
Smilow Cancer Hospital Care Center-Trumbull
City
Trumbull
State/Province
Connecticut
ZIP/Postal Code
06611
Country
United States
Facility Name
Smilow Cancer Hospital Care Center - Waterford
City
Waterford
State/Province
Connecticut
ZIP/Postal Code
06385
Country
United States
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224-9980
Country
United States
Facility Name
Emory University Hospital Midtown
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Emory University Hospital/Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Emory Saint Joseph's Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
University of Kentucky/Markey Cancer Center
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Facility Name
University of Maryland/Greenebaum Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Massachusetts General Hospital Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Wayne State University/Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Weisberg Cancer Treatment Center
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48334
Country
United States
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Siteman Cancer Center at West County Hospital
City
Creve Coeur
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Siteman Cancer Center-South County
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63129
Country
United States
Facility Name
Siteman Cancer Center at Saint Peters Hospital
City
Saint Peters
State/Province
Missouri
ZIP/Postal Code
63376
Country
United States
Facility Name
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Facility Name
UNC Lineberger Comprehensive Cancer Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
University of Pittsburgh Cancer Institute (UPCI)
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Vanderbilt University/Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Virginia Cancer Center
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Virginia Commonwealth University/Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
University of Wisconsin Carbone Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
University Health Network-Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
35033226
Citation
Schoenfeld JD, Giobbie-Hurder A, Ranasinghe S, Kao KZ, Lako A, Tsuji J, Liu Y, Brennick RC, Gentzler RD, Lee C, Hubbard J, Arnold SM, Abbruzzese JL, Jabbour SK, Uboha NV, Stephans KL, Johnson JM, Park H, Villaruz LC, Sharon E, Streicher H, Ahmed MM, Lyon H, Cibuskis C, Lennon N, Jhaveri A, Yang L, Altreuter J, Gunasti L, Weirather JL, Mak RH, Awad MM, Rodig SJ, Chen HX, Wu CJ, Monjazeb AM, Hodi FS. Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy: an open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2022 Feb;23(2):279-291. doi: 10.1016/S1470-2045(21)00658-6. Epub 2022 Jan 13.
Results Reference
derived

Learn more about this trial

Durvalumab and Tremelimumab With or Without High or Low-Dose Radiation Therapy in Treating Patients With Metastatic Colorectal or Non-small Cell Lung Cancer

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