NCT04929041|SuspendedPhase 2FDA Drug

Study Stopped

End of Initial Phase of Multi-phase protocol

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

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2021-06042A082002U10CA180821

Study Type

interventional

Target

427

Locations

1 country

Sites

170

Timeline

RegisteredJun 2021

StartedOct 2022

CompletionDec 2030

Brief 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.

Trial Health

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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial recruitment is currently suspended

Enrollment

427

participants targeted

Target at P75+ for phase_2

Timeline

55mo left

Started Oct 2022

Longer than P75 for phase_2

Geographic Reach

1 country

170 active sites

Status

suspended

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

8.2 years study duration

Study Progress45%

Oct 2022Dec 2030

First Submitted

Initial submission to the registry

June 16, 2021

Completed

2 days until next milestone

First Posted

Study publicly available on registry

June 18, 2021

Completed

1.3 years until next milestone

Study Start

First participant enrolled

October 7, 2022

Completed

8.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 12, 2030

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 12, 2030

Last Updated

May 13, 2026

Status Verified

February 1, 2026

Enrollment Period

8.2 years

First QC Date

June 16, 2021

Last Update Submit

May 12, 2026

Conditions

Stage IIIC Lung Cancer AJCC v8 Stage IV Lung Cancer AJCC v8 Stage IIIB Lung Cancer AJCC v8 Lung Adenocarcinoma Lung Adenosquamous Carcinoma Lung Non-Small Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

Progression-free survival (PFS) (Phase II)
Will be performed on an intent-to-treat (ITT) basis.
From randomization to disease progression or death of all causes, whichever comes first, assessed up to 5 years
Overall survival (OS) (Phase III)
Will be performed on an ITT basis. The comparison of the distributions of OS between treatment arms will be done with a one-sided stratified log-rank test). The rates at various time points (e.g., every 6 months after randomization) and medians of OS for each arm will be estimated using the Kaplan-Meier estimator. The associated 95% confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Hazard ratios will be estimated using a stratified Cox regression model. The final phase III analysis of OS will be considered as "positive" if the stratified log-rank test statistics Z-value greater than the critical value adjusted for type 1 error using group sequential methods. Multivariable Cox models will be used to evaluate the treatment effect on survival time and its interaction with baseline covariates, including stage, systemic therapy, histology and performance status.
From randomization and death of all causes, assessed up to 5 years

Secondary Outcomes (4)

PFS
From randomization to disease progression or death of all causes, whichever comes first, assessed up to 5 years
Objective response rate (ORR)
Up to 5 years
Quality of life
Up to 5 years
Incidence of treatment-related adverse events
Up to 5 years

Study Arms (2)

Arm A (immunotherapy, +/- chemotherapy)

EXPERIMENTAL

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.

Procedure: Biopsy ProcedureProcedure: Biospecimen CollectionProcedure: Computed TomographyProcedure: Echocardiography TestBiological: IpilimumabProcedure: Magnetic Resonance ImagingBiological: NivolumabProcedure: Positron Emission TomographyOther: Quality-of-Life Assessment

Arm B (immunotherapy, +/- chemotherapy, radiation therapy)

EXPERIMENTAL

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.