Phase 2 Proof of Concept Study of Nivolumab and Ipilimumab in Children and Young Adults With Relapsed or Refractory INI1-negative Cancers

Dana-Farber Cancer Institute8 sites in 1 country45 target enrollmentAugust 14, 2020

ConditionsMalignant Rhabdoid Tumor Rhabdoid Tumor of the Kidney Epithelioid Sarcoma Chordoma (Poorly Differentiated or De-differentiated)Atypical Teratoid/Rhabdoid Tumor Other INI1 Negative Tumors (With PI Approval)Other SMARCA4-deficient Malignant Tumors (With PI Approval)

InterventionsNivolumab Ipilimumab

DrugsNivolumab Ipilimumab

Overview

Phase: Phase 2
Intervention: Nivolumab
Conditions: Malignant Rhabdoid Tumor
Sponsor: Dana-Farber Cancer Institute
Enrollment: 45
Locations: 8
Primary Endpoint: Objective Overall Response Rate (Stratum 1)
Status: Active, Not Recruiting
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This clinical trial is studying two immunotherapy drugs (nivolumab and ipilimumab) given together as a possible treatment for INI1-negative tumors.

Detailed Description

This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug or drug combination to learn whether the drug or drug combination works in treating a specific disease. "Investigational" means that the drug combination is being studied. The names of the study drugs involved in this study are: * Nivolumab (OPDIVO) * Ipilimumab (YERYOY) This trial is studying whether nivolumab and ipilimumab work to treat INI1-negative cancers. The U.S. Food and Drug Administration (FDA) has not approved combination nivolumab and ipilimumab for the specific diseases in this study but it has been approved for other diseases. Nivolumab and ipilimumab have been tested in children to find out a safe dose of this combination.

Registry

clinicaltrials.gov

Start Date

August 14, 2020

End Date

June 1, 2026

Last Updated

4 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Dana-Farber Cancer Institute

Responsible Party

Principal Investigator

Suzanne Forrest, MD

Sponsor Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Inclusion Criteria

•All participants must have one of the following histologically confirmed tumors at original diagnosis or relapse:
•Stratum 1
•Malignant rhabdoid tumor (MRT)
•Rhabdoid tumor of the kidney (RTK)
•Epithelioid sarcoma
•Chordoma (poorly differentiated or de-differentiated)
•Other INI1-negative or SMARCA4-deficient malignant tumors (with PI approval)
•Stratum 2
•Atypical teratoid rhabdoid tumor (ATRT)
•Other INI1-negative or SMARCA4-deficient primary CNS malignant tumors (with PI approval)

Exclusion Criteria

•Participants who are receiving any other investigational agents.
•Participants must not be receiving concomitant systemic steroid medications The use of physiologic doses of corticosteroids (up to 5 mg/m2/day prednisone equivalent) may be approved after consultation with the PI (treatment with topical, inhaled or ophthalmic corticosteroid is acceptable)
•Participants with a known history of HIV, hepatitis B, and/or hepatitis C
•Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or any other concurrent disease which in the judgment of the Investigator would make the subject inappropriate for enrollment on this study
•Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
•Has active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy are exceptions. Intermittent use of bronchodilators or local steroid injections are not excluded. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Autoimmune diagnoses not listed must be approved by the Principal Investigator.
•Patients who have received prior solid organ transplantation are not eligible.
•Pregnancy or Breast-Feeding. Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal.
•Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 or anti-CTLA4 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. OX-40, CD137)
•Participants who have received live / attenuated vaccine within 30 days of first dose of study treatment.

Arms & Interventions

Solid Tumor (Stratum 1)

* Patients will receive combination therapy with nivolumab at a predetermined dose and ipilimumab at a predetermined dose day 1 of a 21-day cycle for 4 cycles * Starting with cycle 5, patients will receive nivolumab monotherapy at a predetermined dose on day 1 and day 15 of a 28-day cycle * Patients with INI1-negative relapsed or refractory extracranial solid tumors

Intervention: Nivolumab