Ultra-Rapid Profiling and Drug Screening for Treatment Selection in Patients With Relapsed or Recurrent Rare Brain Tumors (SUPERNOVA-RBT)

Inclusion Criteria:

1. Patients must have a relapse or recurrence of one of the following rare brain tumors:

   • CNS sarcoma (e.g. EWS, CIC, DICER1 altered)
   • BCOR altered tumors (e.g. BCOR ITD; BCOR, BCORL1, EP300, fused)
   • Mesenchymal tumors (e.g. FET::CREB altered tumors)
   • MN1::PATZ1 fused tumors
   • PLAG- altered tumors
   • Astroblastomas/MN-1 altered (e.g. EWSR2BEND2 altered)
   • Unclassifiable tumors
   • Other rare brain tumors: (e.g. recently described, poorly characterized, and/or ambiguous entities)

2. Participant must be a candidate for surgical resection or biopsy.

   • Participants must have surgically accessible disease.

3. Prior therapy

   • The participant must have a relapsed or recurrent rare brain tumor following at least one prior therapy for initial diagnosis or previous recurrence prior to study registration:

   • Surgery followed by observation.
   • Multi-modality therapy: surgery, radiation, and/or chemotherapy

4. Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

   • Biologic agent: Participant must have recovered from any toxicity potentially related to the agent.
   • Last radiation at least 7 days prior to therapy start

5. Karnofsky 50 for participants > 16 years of age and Lansky 50 for participants <16 years of age

6. Corticosteroids: Subjects who are receiving dexamethasone or equivalent must be on a stable or decreasing dose for at least 1 week prior to therapy start.

7. The effects of the agents used in this study on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and 4 months after completion of therapy administration.

8. Adequate neurologic function defined as:

   • Participants with seizure disorders may be enrolled if seizures are well controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug.

9. A legal parent or guardian must be able to understand and agree to sign a written informed consent and assent document, as appropriate.

Exclusion Criteria:

1. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.
2. Women of childbearing potential must not be pregnant or breast-feeding. A negative serum or urine pregnancy test is required prior to start of therapy.