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2025-12-25 @ 12:24 AM
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2025-12-25 @ 10:29 PM
Study NCT ID:
NCT02304458
Status:
COMPLETED
Last Update Posted:
2023-10-17
First Post:
2014-11-26
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Nivolumab With or Without Ipilimumab in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Sarcomas
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase 1/2 Study of Nivolumab in Children, Adolescents, and Young Adults With Recurrent or Refractory Solid Tumors as a Single Agent and in Combination With Ipilimumab
Status:
COMPLETED
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I/II trial studies the side effects and best dose of nivolumab when given with or without ipilimumab to see how well they work in treating younger patients with solid tumors or sarcomas that have come back (recurrent) or do not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether nivolumab works better alone or with ipilimumab in treating patients with recurrent or refractory solid tumors or sarcomas.
Detailed Description:
PRIMARY OBJECTIVES:
I. Determine the tolerability, and define and describe the toxicities of nivolumab administered as a single agent in children with relapsed or refractory solid tumors at the adult recommended dose of 3 mg/kg.
II. Determine if systemic nivolumab exposure in children is similar to the systemic exposure in adults following a 3 mg/kg dose.
III. Determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and define and describe the toxicities of nivolumab plus ipilimumab administered to children with relapsed or refractory solid tumors.
IV. Assess antitumor effects of nivolumab across selected childhood solid tumors in seven expansion cohorts (Parts B1-B6, B8); neuroblastoma (2 cohorts: measurable disease, metaiodobenzylguanidine \[MIBG\] positive only non-measurable disease), osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, Hodgkin lymphoma, and non-Hodgkin lymphoma.
V. Assess antitumor effects of nivolumab in combination with ipilimumab across selected childhood solid tumors in two dose combinations (Part D and Part E).
VI. Characterize the pharmacokinetics of nivolumab alone and in combination with ipilimumab, including area under the curve (AUC), concentration maximum (Cmax), concentration minimum (Cmin), using intensive sampling.
VII. Assess immunogenicity of nivolumab alone and in combination with ipilimumab by measuring anti-drug antibody (ADA) levels.
SECONDARY OBJECTIVES:
I. Conduct exploratory studies of the phenotypic and functional effects of nivolumab (alone and in combination with ipilimumab), as well as changes in antibodies to previously vaccinated viruses, in serum samples.
II. Explore whether correlations exist between PD-L1 expression on tumor and antitumor effects of nivolumab (alone and in combination with ipilimumab) in pediatric solid tumors and to conduct exploratory studies of potential tumor associated biomarkers of response in tumor tissue (at least five out of the following markers: NRAS, BRAF, MEK, KIT, PDGF, TP53, RB1 and BRCA1, Akt phosphorylation, IL-17 or PD-L1).
III. Explore presence of tumor infiltrating lymphocytes and their association with antitumor effects of nivolumab (alone and in combination with ipilimumab).
IV. Conduct exploratory studies of the effect of nivolumab (alone or in combination with ipilimumab) on cytokine levels in serum samples.
V. For Part E, determine tumor mutational burden of diagnostic specimens using FoundationOneCDx testing to explore immune- related gene expression or mutation and its association with antitumor response to nivolumab in combination with ipilimumab.
OUTLINE: This is a phase I, dose-escalation study of nivolumab followed by a phase II study.
PART A (COMPLETED): Patients with recurrent or refractory solid tumors receive nivolumab intravenously (IV) over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PART B (COMPLETED): Patients with neuroblastoma, osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, Hodgkin lymphoma, non-Hodgkin lymphoma, or melanoma receive nivolumab as in Part A.
PART C (COMPLETED):
INDUCTION: Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive nivolumab IV as in Part A. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PART D (COMPLETED):
INDUCTION: Patients with neuroblastoma, osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, Hodgkin lymphoma, non-Hodgkin lymphoma, or melanoma receive nivolumab IV and ipilimumab IV as in Part C. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PART E: Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at approximately 100 days, every 6 months for up to 24 months, and then annually for up to 60 months.
I. Determine the tolerability, and define and describe the toxicities of nivolumab administered as a single agent in children with relapsed or refractory solid tumors at the adult recommended dose of 3 mg/kg.
II. Determine if systemic nivolumab exposure in children is similar to the systemic exposure in adults following a 3 mg/kg dose.
III. Determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and define and describe the toxicities of nivolumab plus ipilimumab administered to children with relapsed or refractory solid tumors.
IV. Assess antitumor effects of nivolumab across selected childhood solid tumors in seven expansion cohorts (Parts B1-B6, B8); neuroblastoma (2 cohorts: measurable disease, metaiodobenzylguanidine \[MIBG\] positive only non-measurable disease), osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, Hodgkin lymphoma, and non-Hodgkin lymphoma.
V. Assess antitumor effects of nivolumab in combination with ipilimumab across selected childhood solid tumors in two dose combinations (Part D and Part E).
VI. Characterize the pharmacokinetics of nivolumab alone and in combination with ipilimumab, including area under the curve (AUC), concentration maximum (Cmax), concentration minimum (Cmin), using intensive sampling.
VII. Assess immunogenicity of nivolumab alone and in combination with ipilimumab by measuring anti-drug antibody (ADA) levels.
SECONDARY OBJECTIVES:
I. Conduct exploratory studies of the phenotypic and functional effects of nivolumab (alone and in combination with ipilimumab), as well as changes in antibodies to previously vaccinated viruses, in serum samples.
II. Explore whether correlations exist between PD-L1 expression on tumor and antitumor effects of nivolumab (alone and in combination with ipilimumab) in pediatric solid tumors and to conduct exploratory studies of potential tumor associated biomarkers of response in tumor tissue (at least five out of the following markers: NRAS, BRAF, MEK, KIT, PDGF, TP53, RB1 and BRCA1, Akt phosphorylation, IL-17 or PD-L1).
III. Explore presence of tumor infiltrating lymphocytes and their association with antitumor effects of nivolumab (alone and in combination with ipilimumab).
IV. Conduct exploratory studies of the effect of nivolumab (alone or in combination with ipilimumab) on cytokine levels in serum samples.
V. For Part E, determine tumor mutational burden of diagnostic specimens using FoundationOneCDx testing to explore immune- related gene expression or mutation and its association with antitumor response to nivolumab in combination with ipilimumab.
OUTLINE: This is a phase I, dose-escalation study of nivolumab followed by a phase II study.
PART A (COMPLETED): Patients with recurrent or refractory solid tumors receive nivolumab intravenously (IV) over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PART B (COMPLETED): Patients with neuroblastoma, osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, Hodgkin lymphoma, non-Hodgkin lymphoma, or melanoma receive nivolumab as in Part A.
PART C (COMPLETED):
INDUCTION: Patients receive nivolumab IV over 60 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive nivolumab IV as in Part A. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PART D (COMPLETED):
INDUCTION: Patients with neuroblastoma, osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, Hodgkin lymphoma, non-Hodgkin lymphoma, or melanoma receive nivolumab IV and ipilimumab IV as in Part C. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PART E: Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 30 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at approximately 100 days, every 6 months for up to 24 months, and then annually for up to 60 months.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2014-01222 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| ADVL1412 | OTHER | Pediatric Early Phase Clinical Trial Network | View | |
| ADVL1412 | OTHER | CTEP | View | |
| UM1CA097452 | NIH | None | https://reporter.nih.gov/quic… | View |