Back to resultsRadical-Dose Image Guided Radiation Therapy in Treating Patients With Metastatic Non-small Cell Lung Cancer Undergoing Immunotherapy
Primary Purpose
Stage IV Non-Small Cell Lung Cancer
Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Image-guided Radiation Therapy
Immunotherapy (physician's choice for standard of care immunotherapy)
Sponsored by
About this trial
This is an interventional treatment trial for Stage IV Non-Small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
- Has stage IV non-small cell lung cancer, or initially stage I-III disease with distant metastatic recurrence
- Age ≥ 18
- Has been receiving anti-PD-1 or anti-PD-L1 immunotherapy for at least four weeks (refer to section 4.2.1)
- Has had restaging imaging after initiation of immunotherapy, at least 4 weeks after pre-immunotherapy baseline imaging. CT or PET/CT of at least chest/upper abdomen must be performed within 4 weeks prior to registration. For patients with history of brain metastases, brain MRI or CT is required within 4 weeks of registration; for other patients brain MRI or CT is required within 12 weeks of registration. Diagnostic PET/CT performed as part of radiation simulation can be used as the restaging imaging.
- Most recent imaging shows measurable disease as defined by RECIST 1.1
Evaluation by a Stanford medical oncologist must show:
- The patient is expected to continue on immunotherapy for at least three more months
- Imaging must show response, stable disease, or modest progression
- If there is modest progression, the patient must be clinically stable in terms of performance status and overall disease-related symptoms
- Has at least one extracranial tumor safely treatable with radical-dose radiation therapy and that has not been previously treated with radiation
- ECOG performance status 0-2
- Has the ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
- Untreated brain metastases, if not planned to be treated in this course of radiation therapy
- Pregnancy or women of childbearing potential not willing/able to use contraception during protocol treatment
Sites / Locations
- Stanford University, School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Immunotherapy plus Image-guided Radiation Therapy
Immunotherapy Alone (Regular Medical Care)
Arm Description
Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while continuing their prior treatment with the treating physician's choice of regular medical care immunotherapy.
Patients who decline to undergo radiation therapy will continue their prior treatment with the treating physician's choice of regular medical care immunotherapy.
Outcomes
Primary Outcome Measures
Progression-free survival
Defined as proportion of patients without Response Evaluation Criteria in Solid Tumors version 1.1 disease progression or death 24 weeks from date of study entry.
Secondary Outcome Measures
Change in circulating tumor deoxyribonucleic acid levels as measured using CAncer Personalized Profiling by deep Sequencing
Will correlate with radiographic response. Plasma biomarkers (e.g. cell free deoxyribonucleic acid level) will be summarized using medians and interquartile ranges; changes in biomarkers will be assessed using the Wilcoxon signed rank test. Correlation of biomarkers with radiographic response will be evaluated using a Wilcoxon rank sum test on patients with and without the event of interest. If feasible, these analyses will be supplemented by more formal analyses with the Cox model.
Change in immune marker levels as measured from peripheral blood using flow cytometry performed by the Human Immune Monitoring Core at Stanford University
Will correlate with radiographic response.
Incidence of acute (0-6 months) and late (> 6 months) grade 3-5 toxicity
Measured with Common Terminology Criteria for Adverse Events version 4.
Overall survival
The electronic medical record will be monitored for patient deaths.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03176173
Brief Title
Radical-Dose Image Guided Radiation Therapy in Treating Patients With Metastatic Non-small Cell Lung Cancer Undergoing Immunotherapy
Official Title
Radical RADiotherapy and Immunotherapy for Metastatic CAncer of the Lung (RRADICAL)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 28, 2017 (Actual)
Primary Completion Date
November 24, 2021 (Actual)
Study Completion Date
February 25, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stanford University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
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
This phase II trial studies how well radical-dose image guided radiation therapy works in treating patients with non-small cell lung cancer that has spread to other places in the body who are undergoing immunotherapy. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radical-dose image guided radiation therapy to patients with non-small cell lung cancer may help to improve response to immunotherapy anti-cancer treatment.
Detailed Description
PRIMARY OBJECTIVES:
I. Determine if progression-free survival at 24 weeks with this treatment combination is improved compared to historical controls who received immunotherapy without radiation therapy.
SECONDARY OBJECTIVES:
I. Assess acute (0-6 months) and late (> 6 months) grade 3-5 toxicity. II. Assess overall survival. III. Correlate circulating tumor deoxyribonucleic acid (DNA) (ratio of post-radiation therapy [RT] to pre-RT level) with radiographic response.
IV. Correlate immune markers in peripheral blood with radiographic response.
TERTIARY OBJECTIVES:
I. Analyze progression-free survival with immune-related response criteria. II. Measure time to discontinuation of study immunotherapy agent. III. Assess patterns of progression.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM I: Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while undergoing standard of care immunotherapy.
Arm II: Patients who decline to undergo radiation therapy receive standard of care immunotherapy.
After completion of study treatment, patients are followed up at 30 days and every 6 months thereafter.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage IV Non-Small Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Immunotherapy plus Image-guided Radiation Therapy
Arm Type
Experimental
Arm Description
Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while continuing their prior treatment with the treating physician's choice of regular medical care immunotherapy.
Arm Title
Immunotherapy Alone (Regular Medical Care)
Arm Type
Active Comparator
Arm Description
Patients who decline to undergo radiation therapy will continue their prior treatment with the treating physician's choice of regular medical care immunotherapy.
Intervention Type
Radiation
Intervention Name(s)
Image-guided Radiation Therapy
Other Intervention Name(s)
IGRT
Intervention Description
Ablative treatment as 50 Gy in 5 or 10 fractions.
Non-ablative treatment as 27 Gy in 3 fractions, or 40 Gy in 10 fractions.
Intervention Type
Drug
Intervention Name(s)
Immunotherapy (physician's choice for standard of care immunotherapy)
Other Intervention Name(s)
biologic therapy
Intervention Description
Continue regular medical care immunotherapy. Other than being an anti-PD-1 or anti-PD-L1 immunotherapy, the agent, dose, and schedule is not specified by protocol.
Primary Outcome Measure Information:
Title
Progression-free survival
Description
Defined as proportion of patients without Response Evaluation Criteria in Solid Tumors version 1.1 disease progression or death 24 weeks from date of study entry.
Time Frame
At 24 weeks after study entry
Secondary Outcome Measure Information:
Title
Change in circulating tumor deoxyribonucleic acid levels as measured using CAncer Personalized Profiling by deep Sequencing
Description
Will correlate with radiographic response. Plasma biomarkers (e.g. cell free deoxyribonucleic acid level) will be summarized using medians and interquartile ranges; changes in biomarkers will be assessed using the Wilcoxon signed rank test. Correlation of biomarkers with radiographic response will be evaluated using a Wilcoxon rank sum test on patients with and without the event of interest. If feasible, these analyses will be supplemented by more formal analyses with the Cox model.
Time Frame
Baseline up to 1 year after study entry
Title
Change in immune marker levels as measured from peripheral blood using flow cytometry performed by the Human Immune Monitoring Core at Stanford University
Description
Will correlate with radiographic response.
Time Frame
Baseline up to 1 year after study entry
Title
Incidence of acute (0-6 months) and late (> 6 months) grade 3-5 toxicity
Description
Measured with Common Terminology Criteria for Adverse Events version 4.
Time Frame
Up to 4 years after study entry
Title
Overall survival
Description
The electronic medical record will be monitored for patient deaths.
Time Frame
Time from study entry to death, assessed up to 4 years after study entry
Other Pre-specified Outcome Measures:
Title
Patterns of response and progression
Description
Patterns of response and progression, including abscopal responses will be measured.
Time Frame
Up to 4 years
Title
Progression free survival
Description
Evaluated with immune-related Response Criteria.
Time Frame
Up to 4 years
Title
Time to discontinuation of study immunotherapy agent
Description
Time to discontinuation of study immunotherapy agent will be measured.
Time Frame
Up to 4 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Has stage IV non-small cell lung cancer, or initially stage I-III disease with distant metastatic recurrence
Age ≥ 18
Has been receiving anti-PD-1 or anti-PD-L1 immunotherapy for at least four weeks (refer to section 4.2.1)
Has had restaging imaging after initiation of immunotherapy, at least 4 weeks after pre-immunotherapy baseline imaging. CT or PET/CT of at least chest/upper abdomen must be performed within 4 weeks prior to registration. For patients with history of brain metastases, brain MRI or CT is required within 4 weeks of registration; for other patients brain MRI or CT is required within 12 weeks of registration. Diagnostic PET/CT performed as part of radiation simulation can be used as the restaging imaging.
Most recent imaging shows measurable disease as defined by RECIST 1.1
Evaluation by a Stanford medical oncologist must show:
The patient is expected to continue on immunotherapy for at least three more months
Imaging must show response, stable disease, or modest progression
If there is modest progression, the patient must be clinically stable in terms of performance status and overall disease-related symptoms
Has at least one extracranial tumor safely treatable with radical-dose radiation therapy and that has not been previously treated with radiation
ECOG performance status 0-2
Has the ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
Untreated brain metastases, if not planned to be treated in this course of radiation therapy
Pregnancy or women of childbearing potential not willing/able to use contraception during protocol treatment
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Gensheimer
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University, School of Medicine
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Radical-Dose Image Guided Radiation Therapy in Treating Patients With Metastatic Non-small Cell Lung Cancer Undergoing Immunotherapy
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