Summary
The current study will use a new treatment approach based on the molecular characteristics of each participant's tumor. The study will test the feasibility in of performing real-time drug screening on tissue taken during surgery in patients with relapsed ultra rare brain tumors (BCOR -altered, MN1-altered, CNS Sarcomas, other rare brain tumors) and of having a specialized tumor board assign a treatment plan based on the results of the drug screening and genomic sequencing. The aim of this trial is to allow every child and young adult with relapsed ultra rare brain tumors to receive the most effective and least toxic therapies currently available and will pave the way for improved understanding and treatment of these tumors in the future. Moreover, if successful, it could serve as a paradigm for personalized medicine programs for other types of cancer.
Detailed Description
Following clinically indicated biopsy or resection, fresh tissue will be submitted for real-time high-throughput drug screening and tumor/paired-normal molecular profiling will be initiated. A specialized tumor board will issue a documented management recommendation within 28 days . Recommendations will integrate successful drug screening, all molecular/pathology data available at the time of review, prior therapy, and clinical context. Later molecular results may prompt an addendum. The treating physician retains responsibility for final treatment decisions.
Eligibility Criteria
Age Range: No minimum to 45 years
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.