Loading clinical trials...

Concurrent or Sequential Immunotherapy and Radiation Therapy in Patients With Metastatic Lung Cancer | Clinical Trials | Clareo Health

ACTIVE_NOT_RECRUITINGPHASE1

Concurrent or Sequential Immunotherapy and Radiation Therapy in Patients With Metastatic Lung Cancer

A Randomized Phase I Trial to Evaluate Concurrent Or Sequential Ipilimumab, Nivolumab, and Stereotactic Body Radiotherapy in Patients With Stage IV Non-Small Cell Lung Cancer (COSINR Study)

NCT03223155•University of Chicago

View on ClinicalTrials.gov

Summary

Trial Design * Patients with stage IV non-small cell lung cancer are randomized to nivolumab/ipilimumab plus either sequential or concurrent stereotactic body radiotherapy (SBRT). * The primary endpoint is the phase I safety endpoint of SBRT dose for each body site. * The same starting SBRT dose levels are used in each arm. If two or more patients experience a dose-limiting toxicity (DLT) at the starting dose level, then the reduced dose level will be used (Section 7.1-Page 72). * DLT is defined as any grade ≥3 toxicity possibly, likely, or definitely related to SBRT plus nivolumab/ipilimumab (the combination and not the individual components). * Irradiated metastases will be grouped into one of five locations, which have different SBRT doses, and the DLTs will be attributed to the relevant organ system. * The starting and decreased SBRT dose levels are found in Table 2 (Page 20). * SBRT will be delivered in 3-5 fractions over the course of 1-1.5 weeks. * Patients in the sequential arm will begin immunotherapy between 1-7 days after completion of SBRT * Given the accrual data for IRB15-1130, the investigators anticipate that approximately 1/3 of patients will contribute metastasis to 2 locations. Since there are 2 arms, and 5 metastasis locations with 6 patients per location for the starting dose level, this translates to 40 patients for the starting dose level, and another 40 patients should each of the 5 locations require de-escalation to the lower dose level. * Secondary endpoints include comparisons of efficacy and toxicity between the arms, as well as interrogation of changes in the immune microenvironment induced by the two approaches.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1\. Have a histologic diagnosis of stage IV NSCLC.
•2\. Be willing and able to provide written informed consent/assent for the trial.
•3\. Be greater than or equal to 18 years of age on day of signing informed consent.
•4\. Have measurable disease based on RECIST 1.1 including at least two metastatic lesions that meet criteria for SBRT radiation.
•a. 0.25 cc to 65 cc of viable tumor (i.e. primary disease or metastases) approximately 5cm in maximal dimension. Tumors larger than 65 cc can be partially treated
•5\. For biopsy identified patients: Be willing to undergo repeat biopsy of a target lesion before treatment and after radiation. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may be exempted from this requirement after consultation with the Principal Investigator.
•6\. Have a performance status of 0 or 1 on the ECOG Performance Scale.
•7\. Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
•Table 1 Adequate Organ Function Laboratory Values System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥ 1,500 /mcL Platelets ≥ 100,000 / mcL Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
•Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤ 1.5 X upper limit of normal (ULN) OR ≥ 50 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
+6 more criteria

Exclusion Criteria

•1\. Has received prior chemotherapy for NSCLC with the exception of neoadjuvant or adjuvant platinum-based chemotherapy for NSCLC completed \>6 months prior to enrollment.
•2\. Has prior exposure to anti-PD1/PD-L1 or anti-CTLA4 therapy.
•3\. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
•4\. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a dose of \>10mg prednisone daily or equivalent at time of first dose of trial treatment.
•5\. Has a known history of active TB (Bacillus Tuberculosis).
•6\. Hypersensitivity to nivolumab, ipilimumab, or any of its excipients.
•7\. Has received radiation therapy within 2 weeks of study drug administration.
•8\. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
•9\. Patients with untreated symptomatic brain metastases. Patients with treated brain metastases will be allowed if brain imaging obtained greater than 7 days from treatment reveals stable disease. Patients with small (\< 3mm) asymptomatic brain metastasis are allowed to enroll. Patients on steroids doses higher than 10 mg of prednisone (or its equivalent) are excluded.
•10\. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
+9 more criteria

Locations (1)

University of Chicago

Chicago, Illinois, United States

Key Dates

Start Date

September 7, 2017

Primary Completion Date

December 1, 2026

Completion Date

December 1, 2027

Last Updated

March 4, 2026

Enrollment

ACTUAL participants

Conditions

Stage IV Small Cell Lung Cancer

Interventions

Nivolumab

DRUG

Ipilimumab

DRUG

Stereotactic body radiation therapy

RADIATION

Predicting Responsiveness in Oncology Patients Based on Host Response Evaluation During Anti Cancer Treatments

NCT04056247

Stage IV Non-small Cell Lung CancerStage IV Malignant Melanoma+3 more

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 4, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions