Ignite Creation Date:
2024-05-06 @ 3:01 PM
Last Modification Date:
2024-10-26 @ 1:41 PM
Study NCT ID:
NCT04500548
Status:
WITHDRAWN
Last Update Posted:
2022-09-10
First Post:
2020-08-04
Brief Title:
Testing the Combination of Two Immunotherapy Drugs Nivolumab and Ipilimumab in Children Adolescent and Young Adult Patients With RelapsedRefractory Cancers That Have an Increased Number of Genetic Changes The 3CI Study
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
3CI Study Childhood Cancer Combination Immunotherapy Phase Ib and Expansion Study of Nivolumab Combination Immunotherapy in Children Adolescent and Young Adult CAYA Patients With RelapsedRefractory Hypermutant Cancers
Status:
WITHDRAWN
Status Verified Date:
2022-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Inadequate accrual rate
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase Ib trial investigates the side effects of the combination of nivolumab and ipilimumab and to see how well they work in treating patients with cancers that have come back relapsed or does not respond to treatment refractory and have an increased number of genetic changes Immunotherapy with monoclonal antibodies such as nivolumab and ipilimumab may help the bodys immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread Tumor mutational burden TMB is the total amount of genetic changes or mutations found in tumor cells Some studies in adults with cancer have shown that patients with a higher TMB an increased number of genetic changes are more likely to respond to immunotherapy drugs There is also evidence that nivolumab and ipilimumab can shrink or stabilize cancer in adult patients with cancer This study is being done to help doctors learn if the combination of nivolumab and ipilimumab can help children adolescents and young adults patients live longer
Detailed Description:
PRIMARY OBJECTIVE
I To confirm the safety and tolerability of nivolumab-based combination therapy in children adolescent and young adult CAYA patients with relapsedrefractory hypermutant cancers including solid tumors central nervous system CNS tumors neuroblastoma and lymphoma
Ia To determine the tolerability define and describe the toxicities and determine the recommended phase 2 dose RP2D of nivolumab and ipilimumab combination therapy in CAYA patients with relapsedrefractory hypermutant cancers
SECONDARY OBJECTIVE
I To assess objective overall response rate ORR to the nivolumab-based combination therapy in CAYA patients with relapsedrefractory hypermutant cancers within the confines of a Phase 1b study
EXPLORATORY OBJECTIVES
I To assess clinical benefit rate CBR objective response and stable disease for at least two 2 protocol reassessments progression-free survival PFS and overall survival OS following nivolumab-based combination therapy in CAYA patients with relapsedrefractory hypermutant cancers
II To explore correlations between tumor genotype including tumor mutation burden TMB specific gene mutations etc and response to nivolumab-based combination therapy in CAYA patients with relapsedrefractory hypermutant cancers
III To discover biomarkers predicting response of hypermutant CAYA cancers undergoing PD-1 blockade including tumor neoantigen formation specific T-cell receptor rearrangements TCRR of tumor infiltrating lymphocytes TILs and detailed characterization and activation of the immune infiltrations including the TILs
IV To explore the use of minimally invasive methods to monitor and predict response to immune checkpoint inhibition in hypermutant cancers including assessment of circulating tumor deoxyribonucleic acid DNA and circulating T-cells immunophenotypic profiling differentiation markers cytokines etc
OUTLINE
PART I Patients undergo collection of tissue samples for TMB level Patients with elevated TMB may be eligible for Part II
PART II Patients are assigned to 1 of 2 dose levels
DOSE LEVEL 1 Patients receive nivolumab intravenously IV over 30-90 minutes and ipilimumab IV over 30 minutes on day 1 Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity Patients then receive nivolumab IV over 30-90 minutes on days 1 and 15 Treatment repeats every 28 days for up to 23 cycles in the absence of disease progression or unacceptable toxicity
DOSE LEVEL -1 Patients receive nivolumab IV over 30-90 minutes on days 1 and 15 Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed up at 30 days and then every 12 weeks for 1 year
I To confirm the safety and tolerability of nivolumab-based combination therapy in children adolescent and young adult CAYA patients with relapsedrefractory hypermutant cancers including solid tumors central nervous system CNS tumors neuroblastoma and lymphoma
Ia To determine the tolerability define and describe the toxicities and determine the recommended phase 2 dose RP2D of nivolumab and ipilimumab combination therapy in CAYA patients with relapsedrefractory hypermutant cancers
SECONDARY OBJECTIVE
I To assess objective overall response rate ORR to the nivolumab-based combination therapy in CAYA patients with relapsedrefractory hypermutant cancers within the confines of a Phase 1b study
EXPLORATORY OBJECTIVES
I To assess clinical benefit rate CBR objective response and stable disease for at least two 2 protocol reassessments progression-free survival PFS and overall survival OS following nivolumab-based combination therapy in CAYA patients with relapsedrefractory hypermutant cancers
II To explore correlations between tumor genotype including tumor mutation burden TMB specific gene mutations etc and response to nivolumab-based combination therapy in CAYA patients with relapsedrefractory hypermutant cancers
III To discover biomarkers predicting response of hypermutant CAYA cancers undergoing PD-1 blockade including tumor neoantigen formation specific T-cell receptor rearrangements TCRR of tumor infiltrating lymphocytes TILs and detailed characterization and activation of the immune infiltrations including the TILs
IV To explore the use of minimally invasive methods to monitor and predict response to immune checkpoint inhibition in hypermutant cancers including assessment of circulating tumor deoxyribonucleic acid DNA and circulating T-cells immunophenotypic profiling differentiation markers cytokines etc
OUTLINE
PART I Patients undergo collection of tissue samples for TMB level Patients with elevated TMB may be eligible for Part II
PART II Patients are assigned to 1 of 2 dose levels
DOSE LEVEL 1 Patients receive nivolumab intravenously IV over 30-90 minutes and ipilimumab IV over 30 minutes on day 1 Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity Patients then receive nivolumab IV over 30-90 minutes on days 1 and 15 Treatment repeats every 28 days for up to 23 cycles in the absence of disease progression or unacceptable toxicity
DOSE LEVEL -1 Patients receive nivolumab IV over 30-90 minutes on days 1 and 15 Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity
After completion of study treatment patients are followed up at 30 days and then every 12 weeks for 1 year
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2020-05617 | REGISTRY | None | None |
| PED-CITN-01 | OTHER | None | None |
| PED-CITN-01 | OTHER | None | None |
| P30CA015704 | NIH | None | None |
| UM1CA154967 | NIH | CTEP | httpsreporternihgovquickSearchUM1CA154967 |