Description:
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.
Title
- 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)
Clinical Trial IDs
- ORG STUDY ID:
IRB-40088
- SECONDARY ID:
NCI-2017-00952
- SECONDARY ID:
IRB-40088
- SECONDARY ID:
LUN0088
- NCT ID:
NCT03176173
Conditions
- Stage IV Non-Small Cell Lung Cancer
Interventions
Drug | Synonyms | Arms |
---|
Immunotherapy (standard of care) | biologic therapy | Arm I (image guided radiation therapy) |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm I (image guided radiation therapy) | Experimental | Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while undergoing standard of care immunotherapy. | - Immunotherapy (standard of care)
|
Arm II (standard of care immunotherapy) | Active Comparator | Patients who decline to undergo radiation therapy receive standard of care immunotherapy. | - Immunotherapy (standard of care)
|
Eligibility Criteria
Inclusion Criteria:
1. Has stage IV non-small cell lung cancer, or initially stage I-III disease with distant
metastatic recurrence
2. Age ≥ 18
3. Has been receiving anti-PD-1 or anti-PD-L1 immunotherapy for at least four weeks
(refer to section 4.2.1)
4. 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.
5. Most recent imaging shows measurable disease as defined by RECIST 1.1
6. Evaluation by a Stanford medical oncologist must show:
1. The patient is expected to continue on immunotherapy for at least three more
months
2. Imaging must show response, stable disease, or modest progression
3. If there is modest progression, the patient must be clinically stable in terms of
performance status and overall disease-related symptoms
7. Has at least one extracranial tumor safely treatable with radical-dose radiation
therapy and that has not been previously treated with radiation
8. ECOG performance status 0-2
9. 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression-free survival |
Time Frame: | At 24 weeks after study entry |
Safety Issue: | |
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. |
Secondary Outcome Measures
Measure: | Change in circulating tumor deoxyribonucleic acid levels as measured using CAncer Personalized Profiling by deep Sequencing |
Time Frame: | Baseline up to 1 year after study entry |
Safety Issue: | |
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. |
Measure: | Change in immune marker levels as measured from peripheral blood using flow cytometry performed by the Human Immune Monitoring Core at Stanford University |
Time Frame: | Baseline up to 1 year after study entry |
Safety Issue: | |
Description: | Will correlate with radiographic response. |
Measure: | Incidence of acute (0-6 months) and late (> 6 months) grade 3-5 toxicity |
Time Frame: | Up to 4 years after study entry |
Safety Issue: | |
Description: | Measured with Common Terminology Criteria for Adverse Events version 4. |
Measure: | Overall survival |
Time Frame: | Time from study entry to death, assessed up to 4 years after study entry |
Safety Issue: | |
Description: | The electronic medical record will be monitored for patient deaths. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Suspended |
Lead Sponsor: | Stanford University |
Last Updated
August 3, 2021