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

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

• 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