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

NCT03176173 | Completed Results DMC

• 3 other identifiers: IRB-40088NCI-2017-00952LUN0088
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Stage IV Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Defined as percentage of participants without disease progression or death at 24 weeks from date of study entry, assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): ≥30% decrease in the sum of the longest diameter of target lesions Overall Response (OR): CR + PR

  24 weeks from study entry

Secondary Outcomes (4)

• Change in Circulating Tumor Deoxyribonucleic Acid Levels as Measured Using CAncer Personalized Profiling by Deep Sequencing

  Baseline (pre-treatment)

• Change in Immune Marker Levels as Measured From Peripheral Blood Using Flow Cytometry Performed by the Human Immune Monitoring Core at Stanford University

  Pre-radiation (up to 14 days before RT) and post-radiation (up to 14 days after completion of RT)

• Number of Participants With Acute (0-6 Months) and Late (> 6 Months) Grade 3-5 Toxicity

  Up to 4 years after study entry

• Overall Survival

  Time from study entry to death, assessed up to 4 years after study entry

Other Outcomes (3)

• Number of Participants With Tumor Response (Including Abscopal Responses)

  Up to 4 years

• Progression Free Survival

  Pre-radiation (up to 14 days before RT) and post-radiation (up to 14 days after completion of RT)

• Time to Discontinuation of Study Immunotherapy Agent

  Up to 4 years

Study Arms (2)

Immunotherapy plus Image-guided Radiation Therapy

EXPERIMENTAL

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.

Radiation: Image-guided Radiation Therapy; Drug: Immunotherapy (physician's choice for standard of care immunotherapy)

Immunotherapy Alone (Regular Medical Care)

ACTIVE COMPARATOR

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

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

Interventions

Image-guided Radiation Therapy 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.

Also known as: IGRT

Immunotherapy plus Image-guided Radiation Therapy

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

Also known as: biologic therapy

Immunotherapy Alone (Regular Medical Care); Immunotherapy plus Image-guided Radiation Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead
• Varian Medical Systems: collaborator

Study Sites (1)

Stanford University, School of Medicine

Palo Alto, California, 94304, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiotherapy, Image-Guided; Immunotherapy; Biological Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Immunomodulation

Limitations and Caveats

Several pre-specified biomarker and imaging outcomes were not analyzed due to lack of funding for laboratory processing or because analyses were deemed not scientifically relevant at the time of final review. No future analyses are planned for these measures.

Results Point of Contact

• Title: Clinical Associate Professor, Radiation Oncology - Radiation Therapy
• Organization: Stanford University

mgens@stanford.edu

(650) 723-6171

Study Officials

• Michael Gensheimer

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor, Radiation Oncology - Radiation Therapy

Study Record Dates

• First Submitted: June 1, 2017
• First Posted: June 5, 2017
• Study Start: June 28, 2017
• Primary Completion: November 24, 2021
• Study Completion: January 31, 2025
• Last Updated: November 5, 2025
• Results First Posted: November 5, 2025

Record last verified: 2025-08

Locations

US (1)