Trials / Suspended
SuspendedNCT04929041
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
A Randomized Phase II/III Trial of Modern Immunotherapy Based Systemic Therapy With or Without Radiation Therapy for PD-L1-Negative, Advanced Non-Small Cell Lung Cancer
- Status
- Suspended
- Phase
- Phase 2 / Phase 3
- Study type
- Interventional
- Enrollment
- 427 (estimated)
- Sponsor
- National Cancer Institute (NCI) · NIH
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
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 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.
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.
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
Interventions
| Type | Name | Description |
|---|---|---|
| PROCEDURE | Biopsy Procedure | Undergo tissue biopsy |
| PROCEDURE | Biospecimen Collection | Undergo blood sample collection |
| PROCEDURE | Computed Tomography | Undergo CT |
| PROCEDURE | Echocardiography Test | Undergo ECHO |
| BIOLOGICAL | Ipilimumab | Given IV |
| PROCEDURE | Magnetic Resonance Imaging | Undergo MRI |
| BIOLOGICAL | Nivolumab | Given IV |
| PROCEDURE | Positron Emission Tomography | Undergo PET |
| OTHER | Quality-of-Life Assessment | Ancillary studies |
| RADIATION | Radiation Therapy | Undergo radiation therapy |
Timeline
- Start date
- 2022-10-07
- Primary completion
- 2030-12-12
- Completion
- 2030-12-12
- First posted
- 2021-06-18
- Last updated
- 2026-04-13
Locations
170 sites across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT04929041. Inclusion in this directory is not an endorsement.