Testing the Addition of Radiation Therapy to the Usual Treatment (Immunotherapy With or Without Chemotherapy) for Advanced Stage Non-small Cell Lung Cancer Patients Who Are PD-L1 Negative
Purpose
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 may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic) whose tumor is also negative for a molecular marker called PD-L1. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. 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.
Conditions
- Lung Adenocarcinoma
- Lung Adenosquamous Carcinoma
- Lung Non-Small Cell Carcinoma
- Stage IIIB Lung Cancer AJCC v8
- Stage IIIC Lung Cancer AJCC v8
- Stage IV Lung Cancer AJCC v8
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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 three
8 gray (Gy) doses of radiation
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- No more than three weeks of treatment with systemic chemotherapy or immunotherapy
for advanced NSCLC
- No more than three weeks of treatment with checkpoint inhibitors for metastatic lung
cancer
- No treatment with chemotherapy or immunotherapy for non-metastatic disease (e.g.,
adjuvant therapy) within 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. Steroid premedication per local standard is allowed
- >= 1 week prior to registration 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 and is allowed
- 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 [registered trademark]) 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 Design
- Phase
- Phase 2/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 Arm A (immunotherapy, +/- chemotherapy) |
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 or patients may receive standard of care systemic immunotherapy. Patients also undergo MRI, CT, or PET throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as ECHO during screening. |
|
|
Experimental Arm B (immunotherapy, +/- chemotherapy, radiation therapy) |
Patients receive 1 of 6 treatment options as in Arm A. Patients also undergo 3 fractions of radiation therapy every other day. Patients also undergo MRI, CT, or PET throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as ECHO during screening. |
|
Recruiting Locations
Little Rock 4119403, Arkansas 4099753 72205
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Berkeley 5327684, California 5332921 94704
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More Details
- NCT ID
- NCT04929041
- Status
- Recruiting
- Sponsor
- National Cancer Institute (NCI)
Detailed Description
PRIMARY OBJECTIVE: I. To assess if radiation 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 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 or patients may receive standard of care systemic immunotherapy. Patients also undergo magnetic resonance imaging (MRI), computed tomography (CT), or positron emission tomography (PET) throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as echocardiography (ECHO) during screening. Arm B: Patients receive nivolumab 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 or patients may receive standard of care systemic immunotherapy. Patients also undergo 3 fractions of radiation therapy every other day. Patients also undergo MRI, CT, or PET throughout the trial. Patients may undergo blood sample collection and tissue biopsy on study as well as ECHO during screening. 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.