Malignant Rhabdoid TumorPhase 2NCT04416568
Study of Nivolumab and Ipilimumab in Children and Young Adults With INI1-Negative Cancers
A Phase 2 study testing Nivolumab and Ipilimumab in people with Malignant Rhabdoid Tumor and Rhabdoid Tumor of the Kidney, run by Dana-Farber Cancer Institute at 8 sites in United States.
Trial summary
This clinical trial is studying two immunotherapy drugs (nivolumab and ipilimumab) given together as a possible treatment for INI1-negative tumors. Read more about this study
- Who is it for?
- Ages 6 months to 40 years
- Conditions the study is for
- Malignant Rhabdoid Tumor, Rhabdoid Tumor of the Kidney, Epithelioid Sarcoma
- What is being tested?
- Nivolumab and Ipilimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 8 sitesUnited States
- Study dates
- 14 Aug 2020to 1 Jul 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 40 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
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- 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
- Measurable disease as defined by RECIST v1.1 (Stratum 1) or RANO criteria (Stratum 2)
- Karnofsky performance status ≥ 50% for participants ≥16 years of age and Lansky performance status ≥ 50% for participants <16 years of age
- Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy. Participants must meet the following minimum washout periods prior to first day of study treatment:
- Myelosuppressive chemotherapy: At least 14 days after the last dose of myelosuppressive chemotherapy
- Radiotherapy
- At least 14 days after local palliative XRT (small port)
- At least 90 days must have elapsed after prior TBI, craniospinal XRT or if >50% radiation of pelvis
- At least 42 days must have elapsed if other substantial BM radiation
- At least 42 days must have passed since last radionuclide therapy (e.g. samarium or radium)
- Small molecule biologic therapy: At least 7 days following the last dose of a nonmonoclonal biologic agent
- Monoclonal antibody: At least 21 days after the last dose
- Myeloid growth factors: At least 14 days following the last dose of long-acting growth factor (e.g. Neulasta) or 7 days following short-acting growth factor
- Stem Cell or Autologous T Cell Infusion: At least 42 days must have elapsed after stem cell or autologous T cell infusion
- Participants must have adequate organ function as defined below
- Bone Marrow Function
- Absolute neutrophil count ≥500/uL
- Platelets ≥50,000/uL and transfusion independent
- Hepatic Function
- Total bilirubin ≤ 1.5 x upper limit of normal for age
- ALT (SGPT) ≤ 3 x upper limit of normal
- Renal function
- A serum creatinine within protocol limits based on age/sex. OR
- Creatinine clearance ≥ 70 mL/min/1.73 m2 for participants with creatinine levels above institutional normal
- Adequate Pulmonary Function Defined as: no evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficient and a pulse oximetry > 92% while breathing room air
- Adequate pancreatic function defined as serum lipase ≤ ULN at baseline
- Negative B-HCG pregnancy test in females of childbearing potential (must be drawn within 24 hours prior to initial administration of nivolumab)
- Women of childbearing potential (WOCBP) receiving nivolumab agree to adhere to contraception for a period of 5 months after the last dose of nivolumab. Men receiving nivolumab and who are sexually active with WOCBP will agree to adhere to contraception for a period of 7 months after the last dose of nivolumab.
- Ability to understand and/or the willingness of the patient (or parent or legally authorized representative, if minor) to provide informed consent using an institutionally approved informed consent procedure.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Children's Healthcare of Atlanta-Egleston
Atlanta, Georgia, 30322
Children's Healthcare of Atlanta-Scottish Rite
Atlanta, Georgia, 30342
Massachusetts General Hospital
Boston, Massachusetts, 02114
Boston Children's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Texas Children's Hospital
Houston, Texas, 77030
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
UCSF Benioff Children's Hospital
San Francisco, California, 94158
About this study
Official title: Phase 2 Proof of Concept Study of Nivolumab and Ipilimumab in Children and Young Adults With Relapsed or Refractory INI1-negative Cancers
This clinical trial is studying two immunotherapy drugs (nivolumab and ipilimumab) given together as a possible treatment for INI1-negative tumors.
Read the 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.
- 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)
- Being tested
- Nivolumab, Ipilimumab
- 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
- Medical subject headings
- Rhabdoid Tumor, Sarcoma, Chordoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called OPDIVO
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
IpilimumabDrug
Also called YERYOY
Combination Therapy: Ipilimumab at predetermined dosage day 1 of a 21-day cycle for 4 cycles
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Nivolumab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
ORR is defined as the percentage of participants who achieved a complete response (CR) or a partial response (PR), as measured by RECIST 1.1 for Stratum 1 and RANO for Stratum 2 per local assessment.
Measured: 12 months
Secondary outcomes (3)
Progression-free Survival (EFS) at 3 Months
Progression-free survival (PFS) was defined as the time from study enrollment until the first occurrence of disease progression, relapse or death due to disease; patients without an event were censored at date of last disease evaluation.
Measured: 3 months
Overall Survival (OS) at 3 Months
OS based on the Kaplan-Meier method is defined as the time from randomization to death. Participants alive are censored at the last date of contact (including lost-to-follow-up) or at the date of withdrawal of consent, if relevant.
Measured: 3 months
Disease Control Rate at 12 Months (DCR12)
DCR12 is defined as the percentage of participants who are progression-free at 12 months. Progression disease (PD) is assessed using RECIST criteria for Stratum 1 and RANO criteria for Stratum 2.
Measured: 12 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2020
- Study start14 Aug 2020
- Primary completion17 Jul 2025
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Malignant Rhabdoid TumorStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Gateway for Cancer Research
- Responsible party
- Principal investigator, Suzanne Forrest, MD, Dana-Farber Cancer Institute
- Investigators
- Suzanne Forrest, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04416568
- Sponsor's protocol ID
- 20-041
- Status last verified
- Sep 2026
- First submitted
- 2 Jun 2020
- Last updated
- 20 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.