Temozolomide + Everolimus in Newly Diagnosed, Recurrent, or Progressive Malignant Glioblastoma Multiforme

• Status: Completed
• Trial end date: 2012-01-06
• Target enrollment: 0
• Participant gender: All

Summary

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

PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with temozolomide in treating patients with newly diagnosed, recurrent, or progressive malignant glioblastoma multiforme.

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

Details

• Lead Sponsor: NCIC Clinical Trials Group
• Treatments: Dacarbazine; Everolimus; Sirolimus; Temozolomide

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant glioblastoma multiforme, meeting 1 of the following criteria:

• Newly diagnosed disease AND meets the following criteria:

• Has undergone prior surgery and radiotherapy with concurrent temozolomide

• No prior chemotherapy except for concurrent low-dose temozolomide given with radiotherapy

• Recurrent or progressive disease after front-line therapy AND meets the following criteria:

• No more than 1 prior chemotherapy regimen in the adjuvant setting

• More than 4 months since last adjuvant treatment

• No prior chemotherapy for recurrence

• Bidimensionally measurable disease, defined as ≥ 1 enhancing lesion ≥ 1 cm x 1 cm by CT scan or MRI, within 21 days of study entry (for patients with recurrent/relapsed disease)

• Patients receiving steroids must be on stable dose for at least 14 days before baseline CT scan or MRI

• Paraffin-embedded sample of primary or metastatic tumor diagnostic specimen must be available

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy ≥ 12 weeks

• Absolute granulocyte count ≥ 1,500/mm³

• Platelet count ≥ 120,000/mm³

• Bilirubin normal

• AST and ALT ≤ 2.5 times upper limit of normal

• Creatinine normal OR creatinine clearance ≥ 60 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No upper gastrointestinal condition or other condition that would preclude compliance with oral medication

• No other prior malignancy except for adequately treated nonmelanoma skin cancer, curatively treated in situ cervical cancer, or other solid tumors curatively treated with no evidence of disease for the past 5 years

• No serious illness or underlying medical condition that would preclude study compliance, including any of the following:

• Significant neurologic or psychiatric disorder that would preclude obtaining informed consent

• Active, ongoing infection

• No known hypersensitivity to everolimus or temozolomide or their components

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 2 weeks since prior surgery and recovered

• At least 4 weeks since prior radiotherapy

• Concurrent enzyme-inducing antiepileptic drugs allowed

• No concurrent inhibitors of cytochrome 3A4 (e.g., ketoconazole and similar antifungals, erythromycin, or diltiazem)

• No other concurrent experimental drugs, anticancer treatment, or investigational therapy

• No concurrent grapefruit juice