Talabostat Combined With Temozolomide or Carboplatin in Treating Young Patients With Relapsed or Refractory Brain Tumors or Other Solid Tumors

• Status: Completed
• Trial end date: 2010-02-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Talabostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving talabostat together with temozolomide or carboplatin may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of talabostat when given together with temozolomide or carboplatin in treating young patients with relapsed or refractory brain tumors or other solid tumors.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institutes of Health Clinical Center (CC)
• Collaborator: National Cancer Institute (NCI)
• Treatments: Carboplatin; Dacarbazine; Temozolomide

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumors, including, but not limited to, any of the following:

• Rhabdomyosarcoma and other soft tissue sarcomas

• Ewing's sarcoma family of tumors

• Osteosarcoma

• Neuroblastoma

• Wilms' tumor

• Hepatic tumors

• Germ cell tumors

• Primary brain tumors

• In patients with brainstem or optic gliomas, requirement for histological confirmation can be waived if biopsy was not performed

• Patients with brainstem gliomas that did not respond to therapy but that are without radiographic evidence of disease progression must have clinical evidence of progression

• Patients with brain tumors must be on stable or tapering dose of corticosteroids for 7 days prior to study entry

• Measurable or evaluable disease

• Relapsed or failed to respond to frontline curative therapy, including any of the following:

• Surgery

• Radiotherapy

• Chemotherapy

• Combination of modalities

• No other potentially curative treatment options available

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Absolute neutrophil count ≥ 1,500/mm^3

• Hemoglobin ≥ 8 mg/dL

• Platelet count ≥ 100,000/mm^3 (platelet transfusion independent)

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• SGPT ≤ 2.5 times ULN

• Creatinine clearance ≥ 60 mL/min OR age-adjusted creatinine* as follows:

• No more than 0.8 mg/dL (for patients ≤ 5 years of age)

• No more than 1.0 mg/dL (for patients 6 to 10 years of age)

• No more than 1.2 mg/dL (for patients 11 to 15 years of age)

• No more than 1.5 mg/dL (for patients > 15 years of age) NOTE: *For patients receiving carboplatin a nuclear glomerular filtration rate study, 24-hour urine collection, and serum creatinine for estimation of creatinine clearance is required if under 15 years of age OR serum creatinine and weight for estimation of creatinine clearance is required if 15-18 years of age

• Patients with history of seizures eligible if seizures controlled by anticonvulsants

• No clinically significant, unrelated systemic illness, including either of the following:

• Serious infections

• Hepatic, renal, or other organ dysfunction that would preclude study treatment

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No generalized pitting peripheral edema

• No sensitivity to valine-proline boronic acid

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered to ≤ grade 1 from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study entry

• Any number of prior chemotherapy regimens allowed

• Prior temozolomide or carboplatin as frontline therapy or in the adjuvant setting allowed provided patient did not experience severe toxicities related to the drug and tumor progressed during this therapy

• At least 3 weeks since last dose of all myelosuppressive chemotherapy

• At least 7 days since last dose of anticancer biologic agents (e.g., retinoids)

• At least 30 days since prior investigational agents

• At least 4 weeks since prior radiotherapy to > 25% of marrow-containing bones (pelvis, spine, or skull) (2 weeks for palliative [limited-port] radiotherapy)

• At least 2 months since prior autologous stem cell transplantation and recovered

• At least 1 week since prior filgrastim (G-CSF), sargramostim (GM-CSF), or epoetin alfa

• At least 2 weeks since prior pegfilgrastim

• No history of allogeneic stem cell transplantation

• No other concurrent anticancer chemotherapy, radiation therapy, or immunotherapy

• No other concurrent investigational agents