PTC299 in Treating Young Patients With Refractory or Recurrent Primary Central Nervous System Tumors

• Status: Completed
• Trial end date: 2015-01-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: PTC299 may stop the growth of tumor cells by blocking blood flow to the tumor.

PURPOSE: This phase I trial is studying the side effects and the best dose of PTC299 in treating young patients with recurrent or refractory primary central nervous system tumors.

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

Details

• Lead Sponsor: Pediatric Brain Tumor Consortium
• Collaborators: National Cancer Institute (NCI); PTC Therapeutics
• Treatments: 6-(4-fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of primary central nervous system (CNS) malignancy at time of diagnosis or recurrence

• Histology verification not required for intrinsic brain stem tumors and optic pathway gliomas

• Must have radiographic evidence of progression

• Recurrent, progressive, or refractory disease to standard therapy and for which there is no known curative therapy

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) 50-100% (patients > 16 years of age) OR Lansky PS 50-100% (patients ≤ 16 years of age)

• Body weight ≥ 15 kg and ≤ 100 kg

• Patients with neurological deficits allowed provided they are stable for ≥ 1 week

• Able to swallow capsules

• ANC ≥ 1,000/μL (unsupported)

• Platelet count ≥ 100,000/μL (unsupported)

• Hemoglobin ≥ 8 g/dL (may be supported)

• Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m^2 OR serum creatinine normal based on age as follows:

• 0.8 mg/dL (≤ 5 years of age)

• 1.0 mg/dL (> 5 to ≤ 10 years of age)

• 1.2 mg/dL (> 10 to ≤ 15 years of age)

• 1.5 mg/dL (> 15 years of age)

• Urine protein/creatinine ratio < 1.0

• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

• ALT and AST ≤ 2.5 times ULN

• Albumin ≥ 2.5 g/dL

• PT and activated PTT ≤ 1.2 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No clinically significant unrelated systemic illness that would compromise the patient's ability to tolerate protocol therapy, or would likely interfere with the study procedures or results, including any of the following:

• Serious infections including ongoing systemic bacterial, fungal, or viral infection

• Significant cardiac, pulmonary, hepatic, or other organ dysfunction

• Willing and able to comply with schedule visits, drug administration plan, laboratory tests, including pharmacokinetic and pharmacodynamic assessments, or other study procedures

• No known coagulopathy or bleeding diathesis

• No known history of drug-induced liver injury

• No CNS, pulmonary, gastrointestinal, or urinary bleeding within the past month

• No uncontrolled systemic hypertension (systolic BP or diastolic BP > 95% percentile for age)

• No alcohol or drug addiction

• Able to tolerate periodic MRI scans and gadolinium contrast

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from the acute toxic of all prior therapy (excluding alopecia and neurotoxicity)

• At least 3 weeks since prior myelosuppressive anticancer chemotherapy (6 weeks for nitrosourea)

• At least 14 days since prior investigational or biological agent

• At least 3 half-lives since prior biological agents that have a prolonged half-life

• At least 3 half-lives since prior monoclonal antibody

• At least 2 weeks since prior local palliative radiotherapy

• At least 6 weeks since prior total-body irradiation, craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis

• At least 90 days since prior allogeneic bone marrow transplantation

• No active graft-versus-host disease

• Concurrent dexamethasone or other corticosteroids allowed provided dose is stable for ≥ 7 days

• At least 1 week since prior colony-forming growth factors (e.g., filgrastim, sargramostim, erythropoietin)

• At least 14 days since long-acting colony-forming growth factor formulations (e.g., pegfilgrastim)

• More than 4 weeks since prior major surgical procedures

• More than 2 weeks since prior intermediate surgical procedures

• More than 7 days since minor surgical procedures

• No other concurrent anticancer or investigational drug therapy