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Report for Clinical Trial NCT03223155

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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)

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.

NCT03223155 Stage IV Small Cell Lung Cancer
MeSH:Lung Neoplasms Small Cell Lung Carcinoma
HPO:Neoplasm of the lung Small cell lung carcinoma

3 Interventions

Name: Nivolumab

Description: Patients in Sequential Arm will begin treatment with nivolumab (given with ipilimumab) between 1-7 days after completion of SBRT. Patients in Concurrent arm will begin treatment with nivolumab (given with ipilimumab) first and will continue treatment within 2 weeks, after completion of SBRT to 2-4 sites. In both arms, patients will receive treatment with nivolumab 3 mg/kg as a 30-minute infusion +/- 10 minutes every 2 weeks for a maximum of 24 months. Patients will receive treatment on days 1, 15, and 29 of each 6 week cycle.
Type: Drug
Group Labels: 2

Concurrent Arm Sequential Arm

Name: Ipilimumab

Description: Patients in Sequential Arm will begin treatment with ipilimumab (given with nivolumab) between 1-7 days after completion of SBRT. Patients in Concurrent arm will begin treatment with ipilimumab (given with nivolumab) first and will continue treatment within 2 weeks, after completion of SBRT to 2-4 sites. In both arms, patients will receive treatment with ipilimumab 1 mg/kg as a 30-minute +/- 10 minutes infusion every 6 weeks for a maximum of 24 months. Patients will receive treatment on day 1 of each 6 week cycle.
Type: Drug
Group Labels: 2

Concurrent Arm Sequential Arm

Name: Stereotactic body radiation therapy

Description: All patients will receive 3 or 5 fractions of radiation as determined by the location of the lesions to be irradiated. There should be a minimum of 40 hours between treatments for an individual lesion. However, a patient may receive radiation for different lesions on consecutive days. Starting dose depends on metastasis locations.
Type: Radiation
Group Labels: 2

Concurrent Arm Sequential Arm


Primary Outcomes

Description: To determine the recommended SBRT dose to various metastatic locations in patients with stage IV NSCLC when delivered prior to or concurrently with nivolumab and ipilimumab.

Measure: Number of serious adverse events

Time: Up to 4 years

Secondary Outcomes

Description: To estimate and compare rates of ≥ grade 3-4 adverse events, by organ system, by CTCAEv4.0 that occur within 3 months from the start of SBRT when given prior to or concurrently with nivolumab/ipilimumab.

Measure: Number of adverse events of grade 3-4 or higher

Time: Up to 4 years

Description: To estimate and compare the rates of long-term adverse events (after 3 months) from the end of SBRT when given prior to or concurrently with nivolumab/ ipilimumab.

Measure: Rate of long term adverse events

Time: Up to 4 years

Description: Summarize and compare the response rate to determine the progression-free survival at 6 months with SBRT given either prior to or concurrently with nivolumab/ipilimumab.

Measure: Rate of response

Time: From the start of treatment until the date of first documented progression or date of death from any cause, whichever comes first, up to 100 months

Description: To determine and compare the control of lesion(s) (SBRT treated and non-treated) when given either prior to or concurrently with nivolumab/ipilimumab.

Measure: Rate of lesion control

Time: Up to 4 years

Description: To evaluate and compare changes in the tumor microenvironment induced by radiation when given prior to or concurrently with nivolumab/ipilimumab.

Measure: Rate of change in tumor microenvironment

Time: Up to 4 years

Description: To evaluate whether response to therapy correlates with PD-L1 expression levels among patients treated with nivolumab/ipilimumab either concurrently or sequential to SBRT.

Measure: Rate of PD-L1 expression levels response

Time: Up to 4 years

Description: To explore whole PBMC by measuring peripheral blood cell T cell subset IFNγ ELISPOT levels throughout the study course and correlate with response to treatment.

Measure: Measure of peripheral blood cell T cell levels

Time: From the start of treatment, not to exceed 4 years

Description: To explore peripheral blood T cell receptor deep sequencing quantification of T cell receptor (TCR) repertoire changes throughout the study course and how TCR repertoire may correlate with progression free survival and/or overall survival.

Measure: Quantification of T cell receptor

Time: From the start of treatment until the date of first documented progression or date of death from any cause, whichever comes first, up to 100 months

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 L858R

- 12. Patients whose tumors known to harbor an exon 19 deletion or exon 21 L858R EGFR mutation must have progressed on or had intolerance to an EGFR TKI. --- L858R ---



HPO Nodes


HPO: