Radical RADiotherapy and Immunotherapy for Metastatic CAncer of the Lung (RRADICAL)

Radical-Dose Image Guided Radiation Therapy in Treating Patients With Metastatic Non-small Cell Lung Cancer Undergoing Immunotherapy

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.

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.

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