Pembrolizumab in Treating Younger Patients With Recurrent, Progressive, or Refractory High-Grade Gliomas, Diffuse Intrinsic Pontine Gliomas, Hypermutated Brain Tumors, Ependymoma or Medulloblastoma

Running, not enrolling · Phase 1

Conditions studied: Constitutional Mismatch Repair Deficiency Syndrome, Lynch Syndrome, Malignant Glioma, Recurrent Brain Neoplasm, Recurrent Childhood Ependymoma, Recurrent Diffuse Intrinsic Pontine Glioma, Recurrent Medulloblastoma, Refractory Brain Neoplasm, Refractory Diffuse Intrinsic Pontine Glioma, Refractory Ependymoma, Refractory Medulloblastoma

In brief

This phase I trial studies the side effects and best dose of pembrolizumab and to see how well it works in treating younger patients with high-grade gliomas (brain tumors that are generally expected to be fast growing and aggressive), diffuse intrinsic pontine gliomas (brain stem tumors), brain tumors with a high number of genetic mutations, ependymoma or medulloblastoma that have come back (recurrent), progressed, or have not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may induce changes in the body's immune system, and may interfere with the ability of tumor cells to grow and spread.

Key facts

Study ID

NCT02359565

Run by

National Cancer Institute (NCI)

People needed

71

Starts

2015-06-03

Expected to finish

2027-01-16

Last updated by the study team

2026-07-20

Who can join

Age: 1 and older, up to 30. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• INCLUSION CRITERIA FOR STRATA A, B, D AND E
• Tumor: patient must have one of the following diagnoses to be eligible:
• Stratum A, currently closed to enrollment: Patients must have a recurrent, progressive or refractory DIPG following radiation therapy with or without chemotherapy
• Histologic diagnosis is not required for patients with typical imaging findings of DIPG (defined as patients with a diffuse expansile mass centered in and involving at least 2/3 of the pons); patients with brainstem tumors who have undergone biopsy with a diagnosis of high-grade glioma or diffuse infiltrating glioma are also eligible
• Stratum B: Patients must have a histologically confirmed diagnosis of a non-brainstem high-grade glioma (NB-HGG) that is recurrent, progressive or refractory following therapy which included radiotherapy; spinal primary disease is eligible
• Stratum D: Patients must have a histologically confirmed diagnosis of ependymoma that is recurrent, progressive or refractory following therapy which included radiotherapy
• Stratum E: Patients must have a histologically confirmed diagnosis of medulloblastoma that is recurrent, progressive or refractory following therapy which included radiotherapy
• Patients must have adequate pre-trial formalin-fixed paraffin-embedded (FFPE) tumor material available for use in the biology studies mutational analysis and genome wide sequencing for each stratum
• Patients with DIPG who have tissue available are requested to submit similar tissue as patients in other strata; however, this is not required for eligibility
• All subjects must have measurable disease in 2-dimensions on MRI scan of the brain; disease should be consistently measured with the two largest perpendicular dimensions
• Patient must be >= 1 but =< 18 years of age at the time of enrollment during the safety portion. Patients < 22 may be enrolled during the efficacy portion of the study.
• Patients must have received prior radiation therapy and/or chemotherapy and recovered from the acute treatment related toxicities (defined as =< grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study; there is no upper limit to the number of prior therapies that is allowed
• Patients must have received their last dose of known myelosuppressive anticancer therapy at least three (3) weeks prior to study enrollment or at least six (6) weeks if prior nitrosourea
• Biologic or investigational agent (anti-neoplastic): Patient must have received their last dose of the investigational or biologic agent >= 7 days prior to study enrollment
• For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration must be discussed with and approved by the study chair
• Monoclonal antibody treatment and/or agents with prolonged half-lives: Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent >= 28 days prior to study enrollment
• Patient must have completed immunotherapy (e.g. tumor vaccines, oncolytic viruses, etc.) at least 42 days prior to enrollment
• Patients must have had their last fraction of:
• Craniospinal irradiation >= 3 months prior to enrollment
• Other substantial bone marrow irradiation >= 6 weeks prior to enrollment
• Local palliative radiation therapy (XRT) (small port) >= 2 weeks
• Patient must be >= 12 weeks since autologous bone marrow/stem cell transplant prior to enrollment
• Patients must be fully recovered from all acute effects of prior surgical intervention
• Both males and females of all races and ethnic groups are eligible for this study
• Patients with neurological deficits should have deficits that are completely stable for a minimum of 1 week (7 days) prior to enrollment

You may not qualify if…

• EXCLUSION CRITERIA FOR STRATA A, B, D AND E
• Concurrent Illness
• Patients with active autoimmune disease or documented history of autoimmune disease/syndrome that requires ongoing systemic steroids or systemic immunosuppressive agents, except
• Patients with vitiligo or resolved asthma/atopy
• Patients with hypothyroidism stable on hormone replacement or Sjogren's syndrome
• History of or ongoing pneumonitis or significant interstitial lung disease Note: This would include non-infectious pneumonitis that required steroid use
• Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results
• Patients with other current malignancies
• Patients with known hypermutated brain tumors including those with CMMRD and Lynch syndrome are ineligible for enrollment in Strata A, B, D and E
• Patients who have received a solid organ transplant
• Patients with bulky tumor on imaging are ineligible; treating physicians are encouraged to contact the study chair to request a rapid central imaging review to confirm fulfilment of these eligibility criteria, if they have concerns
• Bulk tumor is defined as:
• Tumor with evidence of clinically significant uncal herniation or midline shift
• Tumor with diameter of > 5 cm in one dimension on T2/fluid attenuated inversion recovery (FLAIR)
• Tumor that in the opinion of the site investigator, shows significant mass effect in either the brain or spine
• Multi-focal/ metastatic disease:
• Note: Multiple foci of enhancement in a single FLAIR abnormality is permissible and will not exclude the subject
• Patients with multi-focal parenchymal disease are ineligible
• Patients with leptomeningeal metastatic disease are eligible; this includes disease that is discrete from the primary lesion but that has a radiographic appearance consistent with leptomeningeal spread, rather than likely trans-parenchymal spread
• Strata B, D and E - patients whose tumor has a significant component involving the brainstem or with significant fourth ventricular compression are ineligible
• Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible
• Patients who have a known active hepatitis B or hepatitis C infection are ineligible; patient must have documented evidence of negative tests for the presence of hepatitis B surface antigen and hepatitis C (anti-hepatitis C virus [HCV] antibody OR hepatitis [Hep] C RNA-qualitative)
• Patients who have received the last vaccination of a live vaccine =< 30 days prior to enrollment are ineligible; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella, yellow fever, rabies, bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine; seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. Flu-Mist [registered trademark]) are live attenuated vaccines, and must meet timeline for live vaccine
• Patients with a history severe (>= grade 3) hypersensitivity reaction to a monoclonal antibody are ineligible
• Patients who have received previous therapy with an anti-CTLA4, anti-CD137

Where it is running

• Children's Hospital Los Angeles — Los Angeles, California, United States
• Lucile Packard Children's Hospital Stanford University — Palo Alto, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• Children's Healthcare of Atlanta - Arthur M Blank Hospital — Atlanta, Georgia, United States
• Lurie Children's Hospital-Chicago — Chicago, Illinois, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
• Children's Hospital of Pittsburgh of UPMC — Pittsburgh, Pennsylvania, United States
• Saint Jude Children's Research Hospital — Memphis, Tennessee, United States
• Texas Children's Hospital — Houston, Texas, United States
• Hospital for Sick Children — Toronto, Ontario, Canada

Full record on ClinicalTrials.gov

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