Nivolumab With or Without Ipilimumab in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Sarcomas

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

For information regarding Eligibility Criteria, Contacts and Locations, please click HERE.

Purpose
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). Monoclonal antibodies, such as nivolumab and ipilimumab, may block tumor growth in different ways by targeting certain cells. It is not yet known whether nivolumab works better alone or with ipilimumab in treating patients with recurrent or refractory solid tumors or sarcomas.

Primary Outcome Measures:

  • Maximum tolerated dose of nivolumab, defined as the maximum dose at which fewer than one-third of patients experience dose limiting toxicity (Phase I) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Response rate of nivolumab in expanded cohorts of patients with neuroblastoma, osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, Hodgkin lymphoma, and non-Hodgkin lymphoma (Part B) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Response rate of nivolumab, defined as either complete response (CR), partial response (PR), stable disease, or progressive disease, according to the
  • Response Evaluation Criteria in Solid Tumors (Part B) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Response rates will be calculated as the percent of patients whose best response is a CR or PR and confidence intervals will be constructed according to the method of Chang. Will be reported descriptively.
  • RP2D of nivolumab plus ipilimumab (Part C) [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]
    A descriptive summary of all toxicities will be reported.

Other Outcome Measures:

  • Biomarker expression analysis [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Will be evaluated for association with outcome, overall and by tumor type. All of these analyses will be descriptive and exploratory and hypotheses generating in nature.
  • PD-L1 expression [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Analyzed in an exploratory fashion, both using a binary scale (> 5% or < 5% of tumor tissue) and using a continuous scale to evaluate whether there are correlations between PD-L1 expression and antitumor effects.
  • Pharmacodynamic analysis, as determined by degree of PD1 occupancy rate on peripheral blood T cells [ Time Frame: Days 1, 2, 4, 8, and 15 of course 1 ] [ Designated as safety issue: No ]
    Evaluated pre- and post-therapy using flow cytometry. Human anti-human antibody analyses will be measured by Bristol-Myers-Squibb.
  • Pharmacokinetic (PK) parameters of nivolumab [ Time Frame: Days 1, 2, 4, 8, and 15 of course 1, days 1, 2, 4, and 8 of course 2, and day 1 of course 4 (Parts A & B); within 30 min prior to start of nivolumab infusion and immediately prior to ipilimumab on day 1 of courses 1-4 (Part C) ] [ Designated as safety issue: No ]
    The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

Estimated Enrollment: 204
Study Start Date: February 2015
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)

For information regarding Eligibility Criteria, Contacts and Locations, please click HERE.