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NCT06686771PHASE3Recruiting

Radiotherapy to Block Oligoprogression In Metastatic Non-Small-Cell Lung Cancer

Canadian Cancer Trials Group

Start Date

12/16/2025

Completion Date

12/31/2030

Summary

This study is being done to answer the following question: Can the chance of lung cancer growing or spreading be lowered by adding targeted radiotherapy to the usual combination of drugs? This study is being done to find out if this approach is better or worse than the usual approach for lung cancer. The usual approach is defined as the care most people get for non-small cell lung cancer.

Detailed Description

The usual approach for patients who are not in a study and whose disease has gotten worse is to switch treatments. Sometimes, combinations of drugs or radiotherapy are used. The study doctor can explain which treatment may be best. These treatments can reduce symptoms and may stop the tumour from growing for several months or longer.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Metastatic disease (stage IV) detected on imaging and histologically and/or cytologically confirmed NSCLC as per the WHO Classification of Tumors and AJCC 8th Edition TNM Classification, without a driver mutation with an actionable first-line targeted therapy, for whom either ICI alone or combination ICI + chemotherapy is indicated * Oligoprogression on first-line ICI +/- chemotherapy systemic therapy after at least 3 cycles. * All sites of oligoprogression can be safely treated with SBRT or ablative radiotherapy as determined by radiation treatment preplan, including availability and tolerability of necessary technologies (e.g., active breathing control, MRLinac, fiducial insertion, etc.) and accounting for previous radiotherapy overlap. Safety must be assessed and determined by a radiation oncologist. * Patients with treated CNS disease who have radiologic and clinical evidence of stable brain metastases, with no evidence of cavitation or hemorrhage in the brain lesion, are eligible providing that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to randomization). * Candidate for regulatory approved SOC first-line orsecond-line systemic therapy options. * Participants must be ≥ 18 years of age. * ECOG performance status of 0, 1 or 2. * Participants that received prior adjuvant/neoadjuvant/consolidation systemic therapy (including chemotherapy and ICI ) are eligible if at least 6 months have elapsed between the completion of prior therapy and start of first-line treatment for metastatic disease. * Participants must have recovered to ≤ grade 1 from all reversible toxicity related to prior systemic therapy. If participants experienced prior immune-mediated toxicity and have not yet re-initiated ICI therapy, please contact CCTG. Please also contact CCTG if participants have ongoing toxicity ≥ grade 1 felt to be clinically insignificant. * Previous surgery related to NSCLC in the curative or metastatic disease setting is permitted. Previous major surgery is permitted provided that surgery occurred at least 28 days prior to participant enrollment and that wound healing has occurred. * Prior external beam radiation related to NSCLC in the metastatic disease setting is permitted provided a minimum of 14 days (2 weeks) have elapsed between the last dose of radiation and date of enrollment. Patients that received prior external beam radiation therapy in the NSCLC curative disease setting (including the primary lesion) are eligible. Oligoprogressive lesions previously treated with external beam radiation are eligible as long they are clinically asymptomatic, and re-treatment is possible according to the investigator. * Prior conventional, non-stereotactic radiotherapy for palliative purposes is allowed, and if the palliated lesion subsequently progressed but asymptomatic not requiring immediate RT, the lesion can still be counted toward one of the five oligoprogressive lesions. * For Arm 1, SBRT must be initiated within 3 weeks of participant enrollment. * Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life and/or health utility questionnaires in either English, French, or Spanish. * Reimbursement of continued SOC ICI and chemotherapy systemic therapies may not be uniform across all sites. In the event that site/investigator is unable to provide access to the drug, participant will not be eligible for this trial. * Participants must be accessible for treatment and follow-up. Investigators must assure themselves the participants enrolled on this trial will be available for complete documentation of the treatment, adverse events, and follow-up. * Participants of childbearing potential must have agreed to use a highly effective contraceptive method. Exclusion Criteria: * Large-cell neuroendocrine carcinoma (LCNEC), pulmonary carcinoid tumour or mixed small cell and non-small cell lung cancer are not eligible. * Presence of leptomeningeal disease. * Pregnancy. * Serious medical conditions in which radiotherapy of target lesions is contraindicated (e.g., scleroderma, Ataxia Telangiectasia (ATM), interstitial lung disease (ILD), Child-Pugh C liver function). * Any other condition in which in the judgement of the investigator would make the patient inappropriate for study entry. * Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. * Concomitant medications should only exclude participants from trial participation when clinically relevant known or predicted drug-drug interactions or potential overlapping toxicities will impact safety or efficacy; please consult the relevant product monographies. * Concurrent treatment with other anti-cancer therapy, including investigational agents. * Live attenuated vaccination administered within 30 days prior to enrollment/randomization.

Interventions

RADIATION

SBRT

OTHER

First or second-line standard of care therapy

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Conditions

Non-small Cell Lung Cancer

Locations

Mayo Clinic Hospital in Arizona

Phoenix, Arizona 85054

United States

City of Hope Comprehensive Cancer Center

Duarte, California 91010

United States

City of Hope at Irvine Lennar

Irvine, California 92618

United States

Saint Mary's Hospital and Regional Medical Center

Grand Junction, Colorado 81501

United States

CTCA at Southeastern Regional Medical Center

Newnan, Georgia 30265

United States

Saint Luke's Cancer Institute - Boise

Boise, Idaho 83712

United States

Saint Luke's Cancer Institute - Fruitland

Fruitland, Idaho 83619

United States

Saint Luke's Cancer Institute - Meridian

Meridian, Idaho 83642

United States

Saint Luke's Cancer Institute - Nampa

Nampa, Idaho 83687

United States

Alton Memorial Hospital

Alton, Illinois 62002

United States

Northwestern University

Chicago, Illinois 60611

United States

Decatur Memorial Hospital

Decatur, Illinois 62526

United States

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois 60115

United States

Crossroads Cancer Center

Effingham, Illinois 62401

United States

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois 60134

United States

Northwestern Medicine Glenview Outpatient Center

Glenview, Illinois 60026

United States

Northwestern Medicine Grayslake Outpatient Center

Grayslake, Illinois 60030

United States

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois 60045

United States

HSHS Saint Elizabeth's Hospital

O'Fallon, Illinois 62269

United States

Northwestern Medicine Oak Brook

Oak Brook, Illinois 60523

United States

Northwestern Medicine Orland Park

Orland Park, Illinois 60462

United States

Memorial Hospital East

Shiloh, Illinois 62269

United States

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois 60555

United States

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa 50023

United States

Mercy Hospital

Cedar Rapids, Iowa 52403

United States

Oncology Associates at Mercy Medical Center

Cedar Rapids, Iowa 52403

United States

UI Health Care Mission Cancer and Blood - West Des Moines Clinic

Clive, Iowa 50325

United States

Iowa Methodist Medical Center

Des Moines, Iowa 50309

United States

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Des Moines, Iowa 50309

United States

Mercy Medical Center - Des Moines

Des Moines, Iowa 50314

United States

UI Health Care Mission Cancer and Blood - Laurel Clinic

Des Moines, Iowa 50314

United States

UI Healthcare Mission Cancer and Blood - Pella

Pella, Iowa 50219

United States

UI Health Care Mission Cancer and Blood - Waukee Clinic

Waukee, Iowa 50263

United States

Miller-Dwan Hospital

Duluth, Minnesota 55805

United States

Mayo Clinic in Rochester

Rochester, Minnesota 55905

United States

Coborn Cancer Center at Saint Cloud Hospital

Saint Cloud, Minnesota 56303

United States

Saint Francis Medical Center

Cape Girardeau, Missouri 63703

United States

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri 63376

United States

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri 63141

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

Siteman Cancer Center-South County

St Louis, Missouri 63129

United States

Siteman Cancer Center at Christian Hospital

St Louis, Missouri 63136

United States

Nebraska Medicine-Bellevue

Bellevue, Nebraska 68123

United States

Nebraska Medicine-Village Pointe

Omaha, Nebraska 68118

United States

University of Nebraska Medical Center

Omaha, Nebraska 68198

United States

Northwell Health/Center for Advanced Medicine

Lake Success, New York 11042

United States

Mount Sinai Chelsea

New York, New York 10011

United States

Mount Sinai West

New York, New York 10019

United States

Mount Sinai Hospital

New York, New York 10029

United States

Manhattan Eye Ear and Throat Hospital

New York, New York 10065

United States

Lenox Hill Hospital

New York, New York 10075

United States

Queens Cancer Center

Rego Park, New York 11374

United States

University of Rochester

Rochester, New York 14642

United States

Stony Brook University Medical Center

Stony Brook, New York 11794

United States

State University of New York Upstate Medical University

Syracuse, New York 13210

United States

Montefiore Medical Center-Einstein Campus

The Bronx, New York 10461

United States

Montefiore Medical Center - Moses Campus

The Bronx, New York 10467

United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio 43210

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma 73104

United States

Geisinger Medical Center

Danville, Pennsylvania 17822

United States

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania 17033-0850

United States

Geisinger Medical Oncology-Lewisburg

Lewisburg, Pennsylvania 17837

United States

UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion

Mechanicsburg, Pennsylvania 17050

United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania 19107

United States

UPMC-Shadyside Hospital

Pittsburgh, Pennsylvania 15232

United States

Geisinger Wyoming Valley/Henry Cancer Center

Wilkes-Barre, Pennsylvania 18711

United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee 37232

United States

The Don and Sybil Harrington Cancer Center

Amarillo, Texas 79106

United States

VCU Massey Cancer Center at Stony Point

Richmond, Virginia 23235

United States

VCU Massey Comprehensive Cancer Center

Richmond, Virginia 23298

United States

Northwest Wisconsin Cancer Center

Ashland, Wisconsin 54806

United States

Cross Cancer Institute

Edmonton, Alberta T6G 1Z2

Canada

CancerCare Manitoba

Winnipeg, Manitoba R3E 0V9

Canada

Odette Cancer Centre- Sunnybrook Health Sciences Centre

Toronto, Ontario M4N 3M5

Canada

University Health Network-Princess Margaret Hospital

Toronto, Ontario M5G 2M9

Canada