Drug Screening Testing with and without Genomic Testing to Determine an Individualized Treatment Plan in Children and Young Adults with Relapsed Medulloblastoma and Ependymoma

Inclusion Criteria

• PILOT PHASE: Participants must have recurrent medulloblastoma
• PILOT PHASE: Participants must have surgically accessible disease
• PILOT PHASE: The participant must have recurrent medulloblastoma following at least one prior therapy for initial diagnosis or previous recurrence– surgery followed by high dose chemotherapy with stem cell rescue or multi-modality therapy of surgery, radiation and chemotherapy – prior to study registration
• PILOT PHASE: Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study: * Myelosuppressive chemotherapy: Participants must have received their last dose of known myelosuppressive anticancer chemotherapy at least 3 weeks prior to study registration (6 weeks prior if nitrosourea) * Biologic agent: Participant must have recovered from any toxicity potentially related to the agent and received their last dose of the biologic agent no less than 7 days prior to study registration ** For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended to beyond the time during which adverse events are known to occur. The duration of this interval should be discussed with the study chair ** For biologic agents that have a prolonged half-life, the appropriate interval since last treatment should be discussed with the study chair prior to registration * Monoclonal antibody treatment: At least three half-lives must have elapsed prior to registration. Such participants should be discussed with the study chair prior to registration. For bevacizumab, participants must have received last dose >= 32 days prior to study registration * Bone Marrow Transplant: Participant must be: ** >= 6 months since allogeneic bone marrow transplant prior to registration ** >=3 months since autologous bone marrow/stem cell prior to registration
• PILOT PHASE: Participant must be a candidate for surgical resection or biopsy
• PILOT PHASE: Participants must have had their last fraction of local irradiation to primary tumor >= 12 weeks prior to registration; investigators are reminded to review potentially eligible cases to avoid confusion with pseudo-progression
• PILOT PHASE: Participants must have had their last fraction of craniospinal irradiation or total body irradiation >= 12 weeks prior to registration
• PILOT PHASE: Participants must have at least 14 days after local palliative radiation (small-port)
• PILOT PHASE: Age >= 12 months to =< 39 years of age
• PILOT PHASE: Karnofsky >= 50 for participants > 16 years of age and Lansky >= 50 for participants =< 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• PILOT PHASE: Corticosteroids: Subjects who are receiving dexamethasone or equivalent must be on a stable or decreasing dose for at least 1 week prior to registration
• PILOT PHASE: Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 within 7 days prior to study registration
• PILOT PHASE: Platelet count >= 100,000/mm^3 within 7 days prior to study registration (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• PILOT PHASE: Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70mL/min/1.73 m^2 within 7 days prior to study registration OR
• PILOT PHASE: A serum creatinine based on age/sex as follows (within 7 days prior to study registration): * 1 to < 2 years (yrs) 0.6mg/dL (male) or 0.6mg/dL (female) maximum serum creatinine * 2 to < 6 yrs 0.8mg/dL (male) or 0.8mg/dL (female) maximum serum creatinine * 6 to < 10 yrs 1mg/dL (male) or 1mg/dL (female) maximum serum creatinine * 10 to < 13 yrs 1.2mg/dL (male) or 1.2mg/dL (female) maximum serum creatinine * 13 to < 16 yrs 1.5mg/dL (male) or 1.4mg/dL (female) maximum serum creatinine * >= 16 yrs 1.7mg/dL (male) or 1.4mg/dL (female) maximum serum creatinine
• PILOT PHASE: Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age within 7 days prior to study registration
• PILOT PHASE: Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) >= 110 U/L within 7 days prior to study registration
• PILOT PHASE: Serum albumin >= 2 g/dL within 7 days prior to study registration
• PILOT PHASE: 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. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• PILOT PHASE: Participants with seizure disorder may be enrolled if seizures are well controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug
• PILOT PHASE: A legal parent/guardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate
• EFFICACY PHASE: Participants must have recurrent medulloblastoma or recurrent ependymoma previously histologically confirmed. Participants must be experiencing their first or second relapse to be eligible
• EFFICACY PHASE: Participants must have surgically accessible disease
• EFFICACY PHASE: Prior therapy: * The participant must have received at least one prior therapy at the time of initial diagnosis * Relapsed medulloblastoma or relapsed ependymoma are eligible * Participants must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and would be eligible for surgical resection per institutional guidelines ** Patients must have received their last chemotherapy or biologic agent at least 7 days prior to registration ** Monoclonal antibody treatment: > 21 days prior to registration ** Bevacizumab participants must have received last dose >= 21 days prior to study registration
• EFFICACY PHASE: Participant must be a candidate for surgical resection or biopsy with anticipated ability to obtain the minimum tissue requirements for study
• EFFICACY PHASE: Radiation: * Participants must have: ** Had their last fraction of local irradiation to primary tumor ≥ 12 weeks prior to registration **Had their last fraction of craniospinal irradiation or total body irradiation ≥ 12 weeks prior to registration ** At least 14 days after local palliative radiation (small-port)
• EFFICACY PHASE: Age ≥ 12 months to ≤ 39 years of age
• EFFICACY PHASE: Karnofsky >= 50 for participants > 16 years of age and Lansky >= 50 for participants =< 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• EFFICACY PHASE: Corticosteroids: Subjects who are receiving dexamethasone or equivalent must be on a stable or decreasing dose for at least 1 week prior to registration
• EFFICACY PHASE: Peripheral absolute neutrophil count (ANC) >= 750/mm^3 (within 7 days prior to study registration)
• EFFICACY PHASE: Platelet count >= 75,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 7 days prior to study registration)
• EFFICACY PHASE: Hemoglobin ≥ 8 g/dl (within 7 days prior to study registration)
• EFFICACY PHASE: Creatinine clearance or radioisotope GFR >= 70mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows (within 7 days prior to study registration): * 1 to < 2 years 0.6mg/dL (male) or 0.6mg/dL (female) maximum serum creatinine * 2 to < 6 years 0.8mg/dL (male) or 0.8mg/dL (female) maximum serum creatinine * 6 to < 10 years 1mg/dL (male) or 1mg/dL (female) maximum serum creatinine * 10 to < 13 years 1.2mg/dL (male) or 1.2mg/dL (female) maximum serum creatinine * 13 to < 16 years 1.5mg/dL (male) or 1.4mg/dL (female) maximum serum creatinine * >= 16 years 1.7mg/dL (male) or 1.4mg/dL (female) maximum serum creatinine ** The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Centers for Disease Control and Prevention (CDC)
• EFFICACY PHASE: Total bilirubin =< 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert’s syndrome, total bilirubin =< 3 x ULN or direct bilirubin =< 1.5 x ULN (within 7 days prior to study registration)
• EFFICACY PHASE: Alanine aminotransferase (ALT) =< 3 x ULN (within 7 days prior to study registration)
• EFFICACY PHASE: Aspartate aminotransferase (AST) =< 3 x ULN (within 7 days prior to study registration)
• EFFICACY PHASE: 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. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• EFFICACY PHASE: Adequate neurologic function defined as: * Participants with seizure disorder may be enrolled if seizures are well controlled. Participants on non-enzyme inducing anticonvulsants may be excluded pending interaction(s) with study drug
• EFFICACY PHASE: Patients must enroll on PNOC COMP if PNOC COMP is open to accrual at the enrolling institution
• EFFICACY PHASE: A legal parent/guardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate

Exclusion Criteria

• PILOT PHASE: Participants who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• PILOT PHASE: Participants who are receiving any other investigational agents
• PILOT PHASE: Participants must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur. Such participants should also be discussed with study chairs
• PILOT PHASE: Participants who are currently taking any anti-cancer direct therapy. Steroids are not considered anti-cancer therapy
• PILOT PHASE: Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection
• PILOT PHASE: 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
• EFFICACY PHASE: Participants who have had chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• EFFICACY PHASE: Participants who are receiving any other investigational agents
• EFFICACY PHASE: Participants must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur. Such participants should also be discussed with study chairs
• EFFICACY PHASE: Participants who are currently taking any anti-cancer direct therapy. Steroids are not considered anti-cancer therapy
• EFFICACY PHASE: Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection
• EFFICACY PHASE: 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
• EFFICACY PHASE: Participants must not receive any tumor-directed therapy after enrollment, except for surgical resection/ biopsy