SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03223155

Developed by Shray Alag, 2019.
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

Sequential Arm Concurrent 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

Sequential Arm Concurrent 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

Sequential Arm Concurrent 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:
Neoplasm of the lung
Genes 43
WT1 KRAS SLC22A18 STK11 IRF1 AKT1 C11ORF95 PRKN PPP2R1B ERBB2 TRPV3 TSC1 POU6F2 TSC2 EWSR1 RELA KEAP1 REST DIS3L2 SFTPA2 GPC3 MBTPS2 LMNA PTEN BRAF BRCA2 EGFR RB1 TRIP13 PDGFRB TERT SFTPC PIK3CA TRIM28 DICER1 MAP3K8 HPGD SLCO2A1 H19 TP53 NOTCH3 BAP1 WRN
Small cell lung carcinoma