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Durvalumab and Consolidation SBRT Following Chemoradiation for Locally Advanced Stage III Non-Small Cell Lung (358)

Primary Purpose

Stage III Non-small-cell Lung Cancer

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Durvalumab
SBRT
Sponsored by
Brown University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage III Non-small-cell Lung Cancer focused on measuring Lung cancer, NSCLC, Stage III, Post chemoradiation

Eligibility Criteria

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

Inclusion Criteria:

  • Stage III NSCLC.
  • Completion of concurrent chemoradiation:

    • Radiation dose of 60.0 Gy (50-65Gy) using standard fractionation

  • Patients will receive the first dose of durvalumab > 3 weeks and < 7 weeks after their last treatment of chemoradiation (last radiation or chemotherapy treatment, whichever ended last).Sites are required to submit prior treatment (chemotherapy and radiation)
  • Residual tumor volume that is appropriate for SBRT

    • Residual Primary tumor <120cc (approximately 6cm diameter).

  • Absolute neutrophil count ≥ 1,000/uL, platelet ≥ 60,000/uL prior to registration.
  • Total bilirubin ≤ 1.5x upper institutional limit of normal (ULN), and AST and ALT ≤ 3x ULN.
  • ECOG performance status 0 to 1
  • Minimum life expectancy of 12 weeks as determined by treating physician.
  • Age > 18 years.
  • Voluntary, signed written informed consent.
  • Women of childbearing potential must have a negative serum pregnancy test within 7 days of day 1 of treatment (post-menopausal women, defined as surgical menopause or lack or menses >12 months, do not need to have a pregnancy test, document status.)
  • Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 6 months after the last treatment.
  • Resolution of all related toxicities from chemo/RT to < grade 2, except alopecia.
  • Patient must have tissue available from prior biopsy for correlative studies as confirmed by treating physician.

Exclusion Criteria:

  • Disease progression during or after standard chemoradiation
  • Prior thoracic radiation (other than the chemoradiation delivered prior to SBRT)
  • Metastatic disease
  • Uncontrolled severe, intercurrent illness as confirmed by the treating physician.
  • Chemotherapy within 3 weeks from the first treatment on study (day 1).
  • Prior complete resection of all NSCLC (patients could have undergone prior resection as long as it is not complete and the patient meets criteria and staging and tumor volume for registration).
  • Severe, active co-morbidity, defined as follows:

    • Uncontrolled neuropathy ≥ grade 2 regardless of cause;
    • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
    • Transmural myocardial infarction within the last 6 months;
    • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
    • Severe hepatic disease, defined as a diagnosis of Child-Pugh Class B or C hepatic disease.
    • HIV positive with CD4 count < 200 cells/microliter. Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol unless patient is known to be HIV positive and they do not had a CD4 count result within 30 days prior to registration.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment, not inclusive of patients who are HIV positive and who meet criterion above.

Note: Patients who require continuous or intermittent steroid therapy for non-autoimmune conditions, e.g. asthma, osteoarthritis or intravenous contrast allergy, are eligible permitted those patients who receive continuous steroids are limited to a dose of ≤10 mg/day of prednisone (or equivalent). Higher doses are permitted for intermittent therapy, e.g. for contrast allergy, but will need to be approved by BrUOG prior to registration.

  • Has a known history of active tuberculosis
  • Hypersensitivity to Durvalumab or any of its excipients
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Has known history of clinically significant pneumonitis
  • Has an active infection requiring intravenous systemic therapy at the time of registration
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating physician
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial as per the treating physician
  • Is pregnant or breastfeeding
  • Has received prior therapy with an anti-CTLA-4, -PD-1, -PD-L1, or -PD-L2 agent
  • Has a known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA)

Sites / Locations

  • Rhode Island HospitalRecruiting
  • The Miriam HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Durvalumab and SBRT

Arm Description

Durvalumab 10mg/kg x 1 day, dose #1 to occur > 3 weeks and <7 weeks after last chemo/RT and prior to SBRT dose 1 (5-10 day time frame between Durvalumab and SBRT). SBRT boost will consist of 2 fractions delivered to the primary tumor only, over 1-2 weeks between the first and second treatments with durvalumab (see above for time frames). The dose will consist of 20Gy (2 fractions of 10Gy). 3 fractions are allowed for centrally located tumors Dose # 2 of durvalumab, (post SBRT) to be given 1-10 days post last SBRT. Durvalumab then to be given at 10mg/kg Q2 weeks (+/- 4 days) for a total of 12 months (maximum of 26 treatments total)

Outcomes

Primary Outcome Measures

Number of patients experiencing grade 2 or higher toxicities during consolidation SBRT with concurrent durvalumab after chemoradiation for locally advanced stage III NSCLC
This outcome will examine the safety and tolerability of the trial.
Average progression-free survival of chemoradiation followed by SBRT and durvalumab for patients with locally advanced stage III NSCLC.
RECIST 1.1

Secondary Outcome Measures

Overall survival (OS)
Average time to local-regional progression (LRP)
Time to distant metastasis (DM)

Full Information

First Posted
June 22, 2018
Last Updated
January 26, 2023
Sponsor
Brown University
Collaborators
Lifespan
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1. Study Identification

Unique Protocol Identification Number
NCT03589547
Brief Title
Durvalumab and Consolidation SBRT Following Chemoradiation for Locally Advanced Stage III Non-Small Cell Lung
Acronym
358
Official Title
Durvalumab and Consolidation SBRT Following Chemoradiation for Locally Advanced Stage III Non-Small Cell Lung
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 13, 2019 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
October 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Brown University
Collaborators
Lifespan

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Durvalumab is a drug that stimulates the immune system to fight lung cancer. Durvalumab is FDA approved to treat lung cancer. Stereotactic body radiation therapy (SBRT) is a newer radiation treatment that gives fewer, but higher doses of radiation than standard radiation. With SBRT, radiation is focused toward the cancer and away from normal surrounding lung tissue. It is possible that when cancer cells are damaged by SBRT Durvalumab may be more effective in activating the immune system. SBRT is a standard FDA approved treatment for early stage (stage 1) lung cancer and is investigational in patients such as yourself with stage 3 lung cancer. The combination of Durvalumab and SBRT is investigational. This study will investigate the effects, good and bad, of the combination of Durvalumab and SBRT.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage III Non-small-cell Lung Cancer
Keywords
Lung cancer, NSCLC, Stage III, Post chemoradiation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Durvalumab and SBRT
Arm Type
Experimental
Arm Description
Durvalumab 10mg/kg x 1 day, dose #1 to occur > 3 weeks and <7 weeks after last chemo/RT and prior to SBRT dose 1 (5-10 day time frame between Durvalumab and SBRT). SBRT boost will consist of 2 fractions delivered to the primary tumor only, over 1-2 weeks between the first and second treatments with durvalumab (see above for time frames). The dose will consist of 20Gy (2 fractions of 10Gy). 3 fractions are allowed for centrally located tumors Dose # 2 of durvalumab, (post SBRT) to be given 1-10 days post last SBRT. Durvalumab then to be given at 10mg/kg Q2 weeks (+/- 4 days) for a total of 12 months (maximum of 26 treatments total)
Intervention Type
Drug
Intervention Name(s)
Durvalumab
Other Intervention Name(s)
Imfinzi
Intervention Description
Durvalumab10mg/kg Q2 weeks (+/- 4 days) for a total of 12 months (maximum of 26 treatments total)
Intervention Type
Radiation
Intervention Name(s)
SBRT
Other Intervention Name(s)
Stereotactic body radiation
Intervention Description
SBRT boost will consist of 2 fractions delivered to the primary tumor only, over 1-2 weeks between the first and second treatments with durvalumab. The dose will consist of 20Gy (2 fractions of 10Gy) *3 fractions are allowed for centrally located tumors
Primary Outcome Measure Information:
Title
Number of patients experiencing grade 2 or higher toxicities during consolidation SBRT with concurrent durvalumab after chemoradiation for locally advanced stage III NSCLC
Description
This outcome will examine the safety and tolerability of the trial.
Time Frame
Defined as the first 3 months of durvalumab.
Title
Average progression-free survival of chemoradiation followed by SBRT and durvalumab for patients with locally advanced stage III NSCLC.
Description
RECIST 1.1
Time Frame
Every 3 months for 1 year then every 4 months for two years then every 6 months for two years then annually until progression on average for about 5 years.
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Time Frame
Every 2 months for the first 6 months, then every 4 months for 2 years then every 6 months for 2 years then yearly for about 5 years
Title
Average time to local-regional progression (LRP)
Time Frame
Every 3 months for 1 year then every 4 months for two years then every 6 months for two years then annually until progression for about 5 years.
Title
Time to distant metastasis (DM)
Time Frame
Every 3 months for 1 year then every 4 months for two years then every 6 months for two years then annually until progression.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Stage III NSCLC. Completion of concurrent chemoradiation: • Radiation dose of 60.0 Gy (50-65Gy) using standard fractionation Patients will receive the first dose of durvalumab > 3 weeks and < 7 weeks after their last treatment of chemoradiation (last radiation or chemotherapy treatment, whichever ended last).Sites are required to submit prior treatment (chemotherapy and radiation) Residual tumor volume that is appropriate for SBRT • Residual Primary tumor <120cc (approximately 6cm diameter). Absolute neutrophil count ≥ 1,000/uL, platelet ≥ 60,000/uL prior to registration. Total bilirubin ≤ 1.5x upper institutional limit of normal (ULN), and AST and ALT ≤ 3x ULN. ECOG performance status 0 to 1 Minimum life expectancy of 12 weeks as determined by treating physician. Age > 18 years. Voluntary, signed written informed consent. Women of childbearing potential must have a negative serum pregnancy test within 7 days of day 1 of treatment (post-menopausal women, defined as surgical menopause or lack or menses >12 months, do not need to have a pregnancy test, document status.) Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 6 months after the last treatment. Resolution of all related toxicities from chemo/RT to < grade 2, except alopecia. Patient must have tissue available from prior biopsy for correlative studies as confirmed by treating physician. Exclusion Criteria: Disease progression during or after standard chemoradiation Prior thoracic radiation (other than the chemoradiation delivered prior to SBRT) Metastatic disease Uncontrolled severe, intercurrent illness as confirmed by the treating physician. Chemotherapy within 3 weeks from the first treatment on study (day 1). Prior complete resection of all NSCLC (patients could have undergone prior resection as long as it is not complete and the patient meets criteria and staging and tumor volume for registration). Severe, active co-morbidity, defined as follows: Uncontrolled neuropathy ≥ grade 2 regardless of cause; Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months; Transmural myocardial infarction within the last 6 months; Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; Severe hepatic disease, defined as a diagnosis of Child-Pugh Class B or C hepatic disease. HIV positive with CD4 count < 200 cells/microliter. Note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol unless patient is known to be HIV positive and they do not had a CD4 count result within 30 days prior to registration. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment, not inclusive of patients who are HIV positive and who meet criterion above. Note: Patients who require continuous or intermittent steroid therapy for non-autoimmune conditions, e.g. asthma, osteoarthritis or intravenous contrast allergy, are eligible permitted those patients who receive continuous steroids are limited to a dose of ≤10 mg/day of prednisone (or equivalent). Higher doses are permitted for intermittent therapy, e.g. for contrast allergy, but will need to be approved by BrUOG prior to registration. Has a known history of active tuberculosis Hypersensitivity to Durvalumab or any of its excipients Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment Has known history of clinically significant pneumonitis Has an active infection requiring intravenous systemic therapy at the time of registration Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating physician Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial as per the treating physician Is pregnant or breastfeeding Has received prior therapy with an anti-CTLA-4, -PD-1, -PD-L1, or -PD-L2 agent Has a known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Roxanne Wood, BA
Phone
4018633000
Email
roxanne_wood@brown.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hina Khan, MD
Organizational Affiliation
Brown University Oncology Research Group (BrUOG) & Lifespan Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roxanne Wood, BA
Phone
401-863-3000
Email
roxanne_wood@brown.edu
First Name & Middle Initial & Last Name & Degree
Hina Khan, MD
First Name & Middle Initial & Last Name & Degree
Jaroslaw Hepel, MD
Facility Name
The Miriam Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roxanne Wood, BA
Phone
401-863-3000
Email
roxanne_wood@brown.edu
First Name & Middle Initial & Last Name & Degree
Hina Khan, MD

12. IPD Sharing Statement

Learn more about this trial

Durvalumab and Consolidation SBRT Following Chemoradiation for Locally Advanced Stage III Non-Small Cell Lung

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