Lung Cancer Clinical Trial

Testing the Addition of Radiation Therapy to the Usual Treatment (Immunotherapy With or Without Chemotherapy) for Stage IV Non-Small Cell Lung Cancer Patients Who Are PD-L1 Negative

Summary

This phase II/III trial compares the addition of radiation therapy to the usual treatment (immunotherapy with or without chemotherapy) versus (vs.) usual treatment alone in treating patients with non-small cell lung cancer that has spread to nearby tissue or lymph nodes (advanced) or has spread to other places in the body (metastatic) whose tumor is also negative for a molecular marker called PD-L1. Stereotactic body radiation therapy (SBRT) is a type of radiation therapy that uses high energy x-rays to kill tumor cells and shrink tumors. This method uses special equipment to position a patient and precisely deliver radiation to tumors with fewer doses over a shorter period and may cause less damage to normal tissue than conventional radiation therapy. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as carboplatin, pemetrexed, paclitaxel and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. The addition of radiation therapy to usual treatment may stop the cancer from growing and increase the life of patients with advanced non-small cell lung cancer who are PD-L1 negative.

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Full Description

PRIMARY OBJECTIVE:

I. To assess if stereotactic body radiation therapy (SBRT) improves the progression free survival (PFS, phase II portion) and overall survival (OS, phase III portion) of advanced stage non-small cell lung cancer (NSCLC) patients with PD-L1 tumor proportion score (TPS) < 1% who receive immunotherapy with or without chemotherapy.

SECONDARY OBJECTIVES:

I. To estimate and compare the rates of >= grade 3-4 and all grade adverse events by Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0 between the arms.

II. To summarize and compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) between the arms.

III. To determine and compare the objective response rate (ORR) per RECIST between the arms (including at both irradiated and un-irradiated sites).

QUALITY OF LIFE (QOL) OBJECTIVE:

I. To assess the health-related QOL in both treatment arms.

CORRELATIVE SCIENCE OBJECTIVE:

I. To evaluate changes in the peripheral immune microenvironment between the arms.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive 1 of 6 treatment options.

Some patients receive immunotherapy alone whether they have squamous or non-squamous histology.

OPTION 1: Patients receive nivolumab intravenously (IV) over 30 minutes on days 1 and 22 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity.

Patients with non-squamous histology receive 1 of 2 options.

OPTION 2: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, carboplatin IV on days 1 and 22 of cycles 1 and 2, and pemetrexed IV over 10 minutes on days 1 and 22 of each cycle. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity.

OPTION 3: Patients receive nivolumab IV over 30 minutes on days 1 and 22 and ipilimumab IV over 30 minutes on day 1 of each cycle. Patients also receive carboplatin IV on days 1 and 22 of cycle 1 and pemetrexed IV over 10 minutes on days 1 and 22 of cycle 1. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity.

Patients with squamous histology receive 1 of 3 options.

OPTION 4: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Patients also receive carboplatin IV and paclitaxel IV over 1-96 hours on days 1 and 22 of cycles 1 and 2. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity.

OPTION 5: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Patients also receive carboplatin IV on days 1 and 22 of cycles 1 and 2, and nab-paclitaxel IV over 30 minutes on days 1, 8, 15, 22, 29 and 36 of cycles 1 and 2. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity.

OPTION 6: Patients receive nivolumab IV over 30 minutes on days 1 and 22 and ipilimumab IV over 30 minutes on days 1 of each cycle. Patients also receive carboplatin IV and paclitaxel IV over 1-96 hours on days 1 and 22 of cycle 1. Cycles repeat every 6 weeks for 24 months in the absence of disease progression or unacceptable toxicity.

Arm B: Patients receive 1 of 6 treatment options as in Arm A. Patients also undergo 3 fractions of SBRT every other day.

After completion of study treatment, patients are followed up every 3 months for 3 years and then every 6 months for years 4-5 following randomization until disease progression. Following disease progression patients are followed for survival every 6 months for up to 5 years following randomization.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Histologic or cytologic diagnosis of stage IV NSCLC using version American Joint Committee on Cancer (AJCC) 8th edition (includes M1a, M1b, and M1c stage disease). Patients with Stage IIIB and IIIC disease are eligible if they are not a candidate for combined chemotherapy and radiation
PD-L1 expression tumor proportion score (TPS) < 1% in tumor cells. If PD-L1 expression TPS is unevaluable or the testing could not be completed patients are not eligible. The assay must have been performed locally by a Clinical Laboratory Improvement Act (CLIA) (or equivalent) certified laboratory. The type of assay will be recorded
For non-squamous patients only (adenocarcinoma or adenosquamous): EGFR, ALK and ROS1 testing must be done locally. No patients with known actionable EGFR mutations (except exon 20 insertion), ALK or ROS1 mutations that can be treated with oral tyrosine inhibitors
Measurable disease based on RECIST 1.1, including at least two cancerous deposits. At least one deposit must be RECIST measurable (and not to be irradiated) while at least one OTHER deposit (measurable or non-measurable) must meet criteria for stereotactic body radiation therapy (SBRT)
Age >= 18 years
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
No prior systemic chemotherapy or immunotherapy for advanced NSCLC
No prior treatment with checkpoint inhibitors for metastatic lung cancer
Chemotherapy for non-metastatic disease (e.g., adjuvant therapy) or immunotherapy for locally advanced stage III disease is allowed if terminated at least 6 months prior to registration
No systemic immunostimulatory or immunosuppressive drugs, including > 10 mg prednisone equivalent per day, within 2 weeks or 5 half-live of the drug, whichever is shorter
>= 1 week since palliative (including central nervous system [CNS]) radiotherapy to any tumor site
No prior allogeneic tissue/solid organ transplant
No uncontrolled intercurrent illness including, but not limited to, serious ongoing or active infection, symptomatic congestive heart failure, uncontrolled cardiac arrhythmia, unstable angina pectoris, that would limit compliance with study requirements
No current pneumonitis or history of non-infectious pneumonitis that required steroids
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration
No active auto-immune disease that requires systemic therapy within 2 years prior to registration. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid release therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
No known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection
No patients with symptomatic central nervous system metastases and/or carcinomatous meningitis. Patients with small asymptomatic brain metastases are eligible as are patients with treated brain metastases that require no steroids
Not pregnant and not nursing, because this study involves radiation as well as potentially chemotherapy which have known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =< 7 days prior to registration is required
No patients with a "currently active" second malignancy that is progressing or has required active treatment within the last 2 years. Participants with non-melanoma skin cancers or carcinoma in-situ (e.g., breast carcinoma, urothelial carcinoma or cervical cancer in situ) or localized prostate cancer (T1-3, N0, M0) that have undergone potentially curative therapy are eligible
No hypersensitivity (>= grade 3) to immunotherapy and/or any of its excipients
No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g.,FluMist) are live attenuated vaccines and are not allowed. COVID-19 vaccine is allowed
Absolute neutrophil count (ANC) >= 1,500/mm^3
Platelet count >= 100,000/mm^3
Calculated (Calc.) creatinine clearance >= 45 mL/min
Total bilirubin =< 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)

Study is for people with:

Lung Cancer

Phase:

Phase 2

Estimated Enrollment:

100

Study ID:

NCT04929041

Recruitment Status:

Recruiting

Sponsor:

National Cancer Institute (NCI)

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There are 61 Locations for this study

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Mayo Clinic Hospital in Arizona
Phoenix Arizona, 85054, United States More Info
Site Public Contact
Contact
855-776-0015
Steven E. Schild
Principal Investigator
Alta Bates Summit Medical Center-Herrick Campus
Berkeley California, 94704, United States More Info
Site Public Contact
Contact
415-209-2683
[email protected]
Uma Suryadevara
Principal Investigator
City of Hope Antelope Valley
Lancaster California, 93534, United States More Info
Site Public Contact
Contact
800-826-4673
[email protected]
Arya Amini
Principal Investigator
Fremont - Rideout Cancer Center
Marysville California, 95901, United States More Info
Site Public Contact
Contact
530-749-4400
Megan E. Daly
Principal Investigator
University of California Davis Comprehensive Cancer Center
Sacramento California, 95817, United States More Info
Site Public Contact
Contact
916-734-3089
Megan E. Daly
Principal Investigator
Gene Upshaw Memorial Tahoe Forest Cancer Center
Truckee California, 96161, United States More Info
Site Public Contact
Contact
530-582-6450
Megan E. Daly
Principal Investigator
City of Hope Upland
Upland California, 91786, United States More Info
Site Public Contact
Contact
800-826-4673
[email protected]
Arya Amini
Principal Investigator
Beebe South Coastal Health Campus
Frankford Delaware, 19945, United States More Info
Site Public Contact
Contact
302-645-3100
[email protected]
Gregory A. Masters
Principal Investigator
Helen F Graham Cancer Center
Newark Delaware, 19713, United States More Info
Site Public Contact
Contact
302-623-4450
[email protected]
Gregory A. Masters
Principal Investigator
Medical Oncology Hematology Consultants PA
Newark Delaware, 19713, United States More Info
Site Public Contact
Contact
302-623-4450
[email protected]
Gregory A. Masters
Principal Investigator
Beebe Health Campus
Rehoboth Beach Delaware, 19971, United States More Info
Site Public Contact
Contact
302-645-3100
[email protected]
Gregory A. Masters
Principal Investigator
MedStar Washington Hospital Center
Washington District of Columbia, 20010, United States More Info
Site Public Contact
Contact
202-877-8839
Irina G. Veytsman
Principal Investigator
Saint Luke's Cancer Institute - Boise
Boise Idaho, 83712, United States More Info
Site Public Contact
Contact
208-381-2774
eslin[email protected]
Alison K. Conlin
Principal Investigator
Saint Luke's Cancer Institute - Fruitland
Fruitland Idaho, 83619, United States More Info
Site Public Contact
Contact
208-381-2774
[email protected]
Alison K. Conlin
Principal Investigator
Saint Luke's Cancer Institute - Meridian
Meridian Idaho, 83642, United States More Info
Site Public Contact
Contact
208-381-2774
[email protected]
Alison K. Conlin
Principal Investigator
Saint Luke's Cancer Institute - Nampa
Nampa Idaho, 83686, United States More Info
Site Public Contact
Contact
208-381-2774
[email protected]
Alison K. Conlin
Principal Investigator
Saint Luke's Cancer Institute - Twin Falls
Twin Falls Idaho, 83301, United States More Info
Site Public Contact
Contact
208-381-2774
[email protected]
Alison K. Conlin
Principal Investigator
University of Chicago Comprehensive Cancer Center
Chicago Illinois, 60637, United States More Info
Site Public Contact
Contact
773-702-8222
[email protected]
Christine M. Bestvina
Principal Investigator
Carle on Vermilion
Danville Illinois, 61832, United States More Info
Site Public Contact
Contact
800-446-5532
[email protected]
Sinisa Stanic
Principal Investigator
Decatur Memorial Hospital
Decatur Illinois, 62526, United States More Info
Site Public Contact
Contact
217-876-4762
[email protected]
Bryan A. Faller
Principal Investigator
Carle Physician Group-Effingham
Effingham Illinois, 62401, United States More Info
Site Public Contact
Contact
800-446-5532
[email protected]
Sinisa Stanic
Principal Investigator
Crossroads Cancer Center
Effingham Illinois, 62401, United States More Info
Site Public Contact
Contact
217-876-4762
[email protected]
Bryan A. Faller
Principal Investigator
Ingalls Memorial Hospital
Harvey Illinois, 60426, United States More Info
Site Public Contact
Contact
708-915-4673
[email protected]
James A. Wallace
Principal Investigator
Carle Physician Group-Mattoon/Charleston
Mattoon Illinois, 61938, United States More Info
Site Public Contact
Contact
800-446-5532
[email protected]
Sinisa Stanic
Principal Investigator
UC Comprehensive Cancer Center at Silver Cross
New Lenox Illinois, 60451, United States More Info
Site Public Contact
Contact
773-702-8222
[email protected]
Christine M. Bestvina
Principal Investigator
Carle Cancer Center
Urbana Illinois, 61801, United States More Info
Site Public Contact
Contact
800-446-5532
[email protected]
Sinisa Stanic
Principal Investigator
Mary Greeley Medical Center
Ames Iowa, 50010, United States More Info
Site Public Contact
Contact
515-956-4132
Debra M. Prow
Principal Investigator
McFarland Clinic PC - Ames
Ames Iowa, 50010, United States More Info
Site Public Contact
Contact
515-239-4734
[email protected]
Debra M. Prow
Principal Investigator
Medical Oncology and Hematology Associates-West Des Moines
Clive Iowa, 50325, United States More Info
Site Public Contact
Contact
515-241-3305
Richard L. Deming
Principal Investigator
Mercy Cancer Center-West Lakes
Clive Iowa, 50325, United States More Info
Site Public Contact
Contact
515-358-6613
[email protected]
Richard L. Deming
Principal Investigator
Greater Regional Medical Center
Creston Iowa, 50801, United States More Info
Site Public Contact
Contact
515-358-6613
[email protected]
Richard L. Deming
Principal Investigator
Mercy Medical Center - Des Moines
Des Moines Iowa, 50314, United States More Info
Site Public Contact
Contact
515-358-6613
[email protected]
Richard L. Deming
Principal Investigator
Mission Cancer and Blood - Laurel
Des Moines Iowa, 50314, United States More Info
Site Public Contact
Contact
515-241-3305
Richard L. Deming
Principal Investigator
Mercy Medical Center-West Lakes
West Des Moines Iowa, 50266, United States More Info
Site Public Contact
Contact
515-358-6613
[email protected]
Richard L. Deming
Principal Investigator
MaineHealth Cancer Care Center of York County
Sanford Maine, 04073, United States More Info
Site Public Contact
Contact
207-459-1600
Matthew D. Cheney
Principal Investigator
Maine Medical Center- Scarborough Campus
Scarborough Maine, 04074, United States More Info
Site Public Contact
Contact
207-396-8090
[email protected]
Matthew D. Cheney
Principal Investigator
Maine Medical Partners - South Portland
South Portland Maine, 04106, United States More Info
Site Public Contact
Contact
207-396-8670
[email protected]
Matthew D. Cheney
Principal Investigator
Saint Joseph Mercy Hospital
Ann Arbor Michigan, 48106, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Christopher M. Reynolds
Principal Investigator
Saint Joseph Mercy Brighton
Brighton Michigan, 48114, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Christopher M. Reynolds
Principal Investigator
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton Michigan, 48114, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Christopher M. Reynolds
Principal Investigator
Saint Joseph Mercy Canton
Canton Michigan, 48188, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Christopher M. Reynolds
Principal Investigator
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton Michigan, 48188, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Christopher M. Reynolds
Principal Investigator
Saint Joseph Mercy Chelsea
Chelsea Michigan, 48118, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Christopher M. Reynolds
Principal Investigator
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea Michigan, 48118, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Christopher M. Reynolds
Principal Investigator
Genesys Hurley Cancer Institute
Flint Michigan, 48503, United States More Info
Site Public Contact
Contact
810-762-8038
[email protected]
Christopher M. Reynolds
Principal Investigator
Hurley Medical Center
Flint Michigan, 48503, United States More Info
Site Public Contact
Contact
810-762-8038
[email protected]
Christopher M. Reynolds
Principal Investigator
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia Michigan, 48154, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Christopher M. Reynolds
Principal Investigator
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti Michigan, 48197, United States More Info
Site Public Contact
Contact
734-712-7251
[email protected]
Christopher M. Reynolds
Principal Investigator
Saint Francis Medical Center
Cape Girardeau Missouri, 63703, United States More Info
Site Public Contact
Contact
573-334-2230
[email protected]
Bryan A. Faller
Principal Investigator
Delbert Day Cancer Institute at PCRMC
Rolla Missouri, 65401, United States More Info
Site Public Contact
Contact
573-458-7504
[email protected]
Jay W. Carlson
Principal Investigator
Roswell Park Cancer Institute
Buffalo New York, 14263, United States
Mount Sinai Chelsea
New York New York, 10011, United States More Info
Site Public Contact
Contact
212-824-7309
[email protected]
Robert M. Samstein
Principal Investigator
Mount Sinai West
New York New York, 10019, United States More Info
Site Public Contact
Contact
212-824-7309
[email protected]
Robert M. Samstein
Principal Investigator
Mount Sinai Hospital
New York New York, 10029, United States More Info
Site Public Contact
Contact
212-824-7309
[email protected]
Robert M. Samstein
Principal Investigator
Upstate Cancer Center at Oneida
Oneida New York, 13421, United States More Info
Site Public Contact
Contact
315-464-8230
[email protected]
Michael D. Mix
Principal Investigator
Upstate Cancer Center at Oswego
Oswego New York, 13126, United States More Info
Site Public Contact
Contact
315-464-8230
[email protected]
Michael D. Mix
Principal Investigator
State University of New York Upstate Medical University
Syracuse New York, 13210, United States More Info
Site Public Contact
Contact
315-464-5476
Michael D. Mix
Principal Investigator
SUNY Upstate Medical Center-Community Campus
Syracuse New York, 13215, United States More Info
Site Public Contact
Contact
315-464-5476
Michael D. Mix
Principal Investigator
Summa Health System - Akron Campus
Akron Ohio, 44304, United States More Info
Site Public Contact
Contact
330-375-4221
[email protected]
Desiree E. Doncals
Principal Investigator
Cancer Centers of Southwest Oklahoma Research
Lawton Oklahoma, 73505, United States More Info
Site Public Contact
Contact
877-231-4440
Raid Aljumaily
Principal Investigator
University of Oklahoma Health Sciences Center
Oklahoma City Oklahoma, 73104, United States More Info
Site Public Contact
Contact
405-271-8777
[email protected]
Raid Aljumaily
Principal Investigator
Christiana Care Health System-Concord Health Center
Chadds Ford Pennsylvania, 19317, United States More Info
Site Public Contact
Contact
302-623-4450
[email protected]
Gregory A. Masters
Principal Investigator
Geisinger Medical Center
Danville Pennsylvania, 17822, United States More Info
Site Public Contact
Contact
570-271-5251
[email protected]
Eric Kemmerer
Principal Investigator
Penn State Milton S Hershey Medical Center
Hershey Pennsylvania, 17033, United States More Info
Site Public Contact
Contact
717-531-3779
[email protected]
Joseph A. Miccio
Principal Investigator
Geisinger Wyoming Valley/Henry Cancer Center
Wilkes-Barre Pennsylvania, 18711, United States More Info
Site Public Contact
Contact
570-271-5251
[email protected]
Eric Kemmerer
Principal Investigator
Medical University of South Carolina
Charleston South Carolina, 29425, United States More Info
Site Public Contact
Contact
843-792-9321
[email protected]
Mariam Alexander
Principal Investigator
Gundersen Lutheran Medical Center
La Crosse Wisconsin, 54601, United States More Info
Site Public Contact
Contact
608-775-2385
[email protected]
Michael O. Ojelabi
Principal Investigator
Mayo Clinic Health System-Franciscan Healthcare
La Crosse Wisconsin, 54601, United States More Info
Site Public Contact
Contact
855-776-0015
Steven E. Schild
Principal Investigator
ProHealth D N Greenwald Center
Mukwonago Wisconsin, 53149, United States More Info
Site Public Contact
Contact
[email protected]
Timothy R. Wassenaar
Principal Investigator
ProHealth Oconomowoc Memorial Hospital
Oconomowoc Wisconsin, 53066, United States More Info
Site Public Contact
Contact
262-928-7878
Timothy R. Wassenaar
Principal Investigator
UW Cancer Center at ProHealth Care
Waukesha Wisconsin, 53188, United States More Info
Site Public Contact
Contact
262-928-5539
[email protected]
Timothy R. Wassenaar
Principal Investigator

How clear is this clinincal trial information?

Study is for people with:

Lung Cancer

Phase:

Phase 2

Estimated Enrollment:

100

Study ID:

NCT04929041

Recruitment Status:

Recruiting

Sponsor:


National Cancer Institute (NCI)

How clear is this clinincal trial information?

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