Dysautonomia International

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

Purpose

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.

Condition

Non-small Cell Lung Cancer

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

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.

Study Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental SBRT/Radiotherapy followed by standard of care therapy		Radiation: SBRT Please refer to the current NCCN NSCLC guidelines for possible treatment options
Active Comparator Systemic therapy at the investigator's discretion, no SBRT		Other: First or second-line standard of care therapy Please refer to the current NCCN NSCLC guidelines for possible treatment options.

Recruiting Locations

City of Hope Comprehensive Cancer Center
Duarte, California 91010

Contact:
Site Public Contact
800-826-4673
becomingapatient@coh.org

City of Hope at Irvine Lennar
Irvine, California 92618

Contact:
Site Public Contact
877-467-3411

Saint Mary's Hospital and Regional Medical Center
Grand Junction, Colorado 81501

Contact:
Site Public Contact
303-777-2663
ccrp@co-cancerresearch.org

Saint Luke's Cancer Institute - Boise
Boise, Idaho 83712

Contact:
Site Public Contact
208-381-2774
eslinget@slhs.org

Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho 83619

Contact:
Site Public Contact
208-381-2774
eslinget@slhs.org

Saint Luke's Cancer Institute - Meridian
Meridian, Idaho 83642

Contact:
Site Public Contact
208-381-2774
eslinget@slhs.org

Saint Luke's Cancer Institute - Nampa
Nampa, Idaho 83687

Contact:
Site Public Contact
208-381-2774
eslinget@slhs.org

Alton Memorial Hospital
Alton, Illinois 62002

Contact:
Site Public Contact
618-463-7323

Northwestern University
Chicago, Illinois 60611

Contact:
Site Public Contact
312-695-1301
cancer@northwestern.edu

Decatur Memorial Hospital
Decatur, Illinois 62526

Contact:
Site Public Contact
217-876-4762
morganthaler.jodi@mhsil.com

Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois 60115

Contact:
Site Public Contact
630-352-5360
Donald.Smith3@nm.org

Crossroads Cancer Center
Effingham, Illinois 62401

Contact:
Site Public Contact
217-876-4762
morganthaler.jodi@mhsil.com

Northwestern Medicine Cancer Center Delnor
Geneva, Illinois 60134

Contact:
Site Public Contact
630-352-5360
Donald.Smith3@nm.org

Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois 60026

Contact:
Site Public Contact
312-695-1102

Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois 60030

Contact:
Site Public Contact
312-695-1102

Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois 60045

Contact:
Site Public Contact
cancertrials@northwestern.edu

HSHS Saint Elizabeth's Hospital
O'Fallon, Illinois 62269

Contact:
Site Public Contact
217-876-4762
morganthaler.jodi@mhsil.com

Northwestern Medicine Oak Brook
Oak Brook, Illinois 60523

Contact:
Site Public Contact
nctnprogram_rhlccc@northwestern.edu

Northwestern Medicine Orland Park
Orland Park, Illinois 60462

Contact:
Site Public Contact
nctnprogram_rhlccc@northwestern.edu

Memorial Hospital East
Shiloh, Illinois 62269

Contact:
Site Public Contact
314-747-9912
dschwab@wustl.edu

Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois 60555

Contact:
Site Public Contact
630-352-5360
Donald.Smith3@nm.org

Mercy Hospital
Cedar Rapids, Iowa 52403

Contact:
Site Public Contact
319-365-4673

Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa 52403

Contact:
Site Public Contact
319-363-2690

Miller-Dwan Hospital
Duluth, Minnesota 55805

Contact:
Site Public Contact
218-786-3308
CancerTrials@EssentiaHealth.org

Saint Francis Medical Center
Cape Girardeau, Missouri 63703

Contact:
Site Public Contact
573-334-2230
sfmc@sfmc.net

Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri 63376