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

NCT ID: NCT03176173

Last Updated: 2025-11-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-28
• Study Completion Date: 2025-01-31

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.

Conditions

Stage IV Non-Small Cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Immunotherapy plus Image-guided Radiation Therapy

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.

Group Type: EXPERIMENTAL

Image-guided Radiation Therapy

Intervention Type: RADIATION

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.

Immunotherapy (physician's choice for standard of care immunotherapy)

Intervention Type: DRUG

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.

Immunotherapy Alone (Regular Medical Care)

Patients who decline to undergo radiation therapy will continue their prior treatment with the treating physician's choice of regular medical care immunotherapy.

Group Type: ACTIVE_COMPARATOR

Immunotherapy (physician's choice for standard of care immunotherapy)

Intervention Type: DRUG

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.

Interventions

Image-guided Radiation Therapy

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: RADIATION

Immunotherapy (physician's choice for standard of care immunotherapy)

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.

Intervention Type: DRUG

Other Intervention Names

IGRT; biologic therapy

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Varian Medical Systems

INDUSTRY

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Michael Francis Gensheimer

Clinical Associate Professor, Radiation Oncology - Radiation Therapy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Gensheimer

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University, School of Medicine

Palo Alto, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

NCI-2017-00952

Identifier Type: REGISTRY

Identifier Source: secondary_id

LUN0088

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-40088

Identifier Type: -

Identifier Source: org_study_id