Temozolomide and O6-Benzylguanine in Treating Children With Recurrent Brain Tumors

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Phase I trial to study the safety of combining O6-benzylguanine with temozolomide in treating children who have recurrent or refractory brain tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. O6-benzylguanine may increase the effectiveness of temozolomide by making tumor cells more sensitive to the drug.

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

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Dacarbazine; O(6)-benzylguanine; Temozolomide

Criteria

Inclusion Criteria:

• Recurrent or refractory pediatric brain tumors; a histopathologic diagnosis from either the initial presentation or at the time of recurrence is required for all but brain stem gliomas

• Karnofsky or Lansky ≥ 60%

• Life expectancy > 8 weeks

• Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to study entry

• Chemotherapy: No more than 2 previous chemotherapy/biologic therapy regimens; evidence of recovery from prior chemotherapy/biologic therapy; no myelosuppressive chemotherapy within 3 weeks (6 weeks if a nitrosourea agent) of study entry; patients who have received temozolomide are eligible if they have not received the drug in the past 3 months and did not experience any non-hematopoietic Grade 3/4 toxicity with prior temozolomide therapy

• XRT: ≥ 3 months prior to study entry for craniospinal irradiation (≥ 18 Gy); ≥ 4 weeks for local radiation to primary tumor; and ≥ 2 weeks prior to study entry for focal irradiation to symptomatic metastatic sites

• Bone Marrow Transplant: ≥ 6 months prior to study entry

• Anti-convulsants: Patients will be eligible for this study even if they are receiving anti-convulsants

• Growth factors: Off all colony forming growth factor(s) > 2 weeks prior to study entry (G-CSF, GM-CSF, Erythropoietin)

• Dexamethasone: Patients who are receiving dexamethasone must be on a stable dose for at least 1 week prior to study entry

• ANC > 1,000/μl

• Platelets > 100,000/μl

• Hemoglobin > 8g/dl

• Patients may have bone marrow involvement by disease; platelet and Hgb counts must be transfusion independent

• Creatinine ≤ 1.5 times institutional normal for age

• Or GFR > 70 ml/min/1.73m^2

• Bilirubin ≤ upper limit of normal for age

• SGPT (ALT) < and SGOT (AST) < 2.5X institutional normal

• No overt renal, hepatic, cardiac or pulmonary disease

• Female patients of childbearing potential must have negative serum or urine pregnancy test; patient must not be pregnant or breast-feeding; while no known teratogenic effects are known for O6-BG so far, there is little data to address this specifically; as such, the prudent approach is to exclude pregnant and breastfeeding patients until further data is available

• Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study

• Signed informed consent according to institutional guidelines must be obtained and patients must begin therapy within seven (7) days of registration

Exclusion Criteria:

• Patients must not be receiving any other anticancer or experimental drug therapy

• Patients with a history of hypersensitivity to dacarbazine, temozolomide or polyethylene glycol are excluded