Study of Nivolumab and Ipilimumab in Children and Young Adults With INI1-Negative Cancers

NCT04416568 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20-041
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 8

Brief Summary

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

Conditions

Malignant 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)

Keywords

Malignant Rhabdoid Tumor; Rhabdoid Tumor of the Kidney; Epithelioid Sarcoma; Chordoma (poorly differentiated or de-differentiated); Atypical Teratoid/Rhabdoid Tumor; INI1 negative tumors; SMARCA4-deficient malignant tumors

Outcome Measures

Primary Outcomes (2)

• Objective Overall Response Rate (Stratum 1)

  Based on Response Evaluation in Solid Tumors (RECIST) version 1.1

  12 months

• Objective Overall Response Rate (Stratum 2)

  Based on Response Assessment in Neuro-Oncology (RANO) Criteria

  12 months

Secondary Outcomes (4)

• Progression-free survival (PFS)

  3 years

• Overall survival (OS)

  3 years

• Disease control rate at 12 months

  12 Months

• Occurrence of toxicities (Grade 3-5 per CTCAE)

  13 months

Study Arms (2)

Solid Tumor (Stratum 1)

EXPERIMENTAL

* 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

Drug: Nivolumab; Drug: Ipilimumab

CNS (Stratum 2)

EXPERIMENTAL

* 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 CNS tumors

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

Combination Therapy: Nivolumab at predetermined dosage day 1 of a 21-day cycle for 4 cycles. Monotherapy: Starting with cycle 5 nivolumab at predetermined dosage on day 1 and day 15 of a 28-day cycle

Also known as: OPDIVO

CNS (Stratum 2); Solid Tumor (Stratum 1)

Ipilimumab DRUG

Combination Therapy: Ipilimumab at predetermined dosage day 1 of a 21-day cycle for 4 cycles

Also known as: YERYOY

CNS (Stratum 2); Solid Tumor (Stratum 1)

Eligibility Criteria

• Age: 6 Months - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)
• All participants must have tumor assessment at original diagnosis or relapse showing the following:
• Loss of INI1 confirmed by immunohistochemistry (IHC), OR
• Molecular confirmation of tumor bi-allelic SMARCB1 (INI1) loss or mutation when INI1 IHC is equivocal or unavailable
• Loss of SMARCA4 confirmed by IHC or molecular confirmation of tumor bi-allelic SMARCA4 loss or mutation when SMARCA4 is equivocal or unavailable
• Relapsed or refractory disease and no standard treatment options as determined by locally or regionally available standards of care and treating physician's discretion

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Gateway for Cancer Research: collaborator

Study Sites (8)

UCSF Benioff Children's Hospital

San Francisco, California, 94158, United States

Location

Children's Healthcare of Atlanta-Egleston

Atlanta, Georgia, 30322, United States

Location

Children's Healthcare of Atlanta-Scottish Rite

Atlanta, Georgia, 30342, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Rhabdoid Tumor; Sarcoma; Chordoma

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective and Soft Tissue; Neoplasms, Germ Cell and Embryonal

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Suzanne Forrest, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: June 2, 2020
• First Posted: June 4, 2020
• Study Start: August 14, 2020
• Primary Completion: July 17, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (8)