Nivolumab With or Without Ipilimumab in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Sarcomas
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02304458 |
Recruitment Status :
Completed
First Posted : December 2, 2014
Results First Posted : January 10, 2023
Last Update Posted : October 17, 2023
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Tracking Information | ||||
---|---|---|---|---|
First Submitted Date ICMJE | November 26, 2014 | |||
First Posted Date ICMJE | December 2, 2014 | |||
Results First Submitted Date ICMJE | October 24, 2022 | |||
Results First Posted Date ICMJE | January 10, 2023 | |||
Last Update Posted Date | October 17, 2023 | |||
Actual Study Start Date ICMJE | March 30, 2015 | |||
Actual Primary Completion Date | September 30, 2021 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
|
|||
Original Primary Outcome Measures ICMJE |
|
|||
Change History | ||||
Current Secondary Outcome Measures ICMJE |
|
|||
Original Secondary Outcome Measures ICMJE | Not Provided | |||
Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures |
|
|||
Descriptive Information | ||||
Brief Title ICMJE | Nivolumab With or Without Ipilimumab in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Sarcomas | |||
Official Title ICMJE | 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 | |||
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. |
|||
Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 1 Phase 2 |
|||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
|||
Condition ICMJE |
|
|||
Intervention ICMJE |
|
|||
Study Arms ICMJE | Experimental: Treatment (nivolumab, ipilimumab)
See Detailed Description
Interventions:
|
|||
Publications * |
|
|||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
||||
Recruitment Information | ||||
Recruitment Status ICMJE | Completed | |||
Actual Enrollment ICMJE |
140 | |||
Original Estimated Enrollment ICMJE |
160 | |||
Actual Study Completion Date ICMJE | March 31, 2023 | |||
Actual Primary Completion Date | September 30, 2021 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
|
|||
Sex/Gender ICMJE |
|
|||
Ages ICMJE | 12 Months to 30 Years (Child, Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | Canada, United States | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT02304458 | |||
Other Study ID Numbers ICMJE | NCI-2014-01222 NCI-2014-01222 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) ADVL1412 ( Other Identifier: Pediatric Early Phase Clinical Trial Network ) ADVL1412 ( Other Identifier: CTEP ) UM1CA097452 ( U.S. NIH Grant/Contract ) |
|||
Has Data Monitoring Committee | Yes | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE | Not Provided | |||
Current Responsible Party | National Cancer Institute (NCI) | |||
Original Responsible Party | Same as current | |||
Current Study Sponsor ICMJE | National Cancer Institute (NCI) | |||
Original Study Sponsor ICMJE | Same as current | |||
Collaborators ICMJE | Not Provided | |||
Investigators ICMJE |
|
|||
PRS Account | National Cancer Institute (NCI) | |||
Verification Date | September 2023 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |