A Modified Phase I/II Trial Of Rapamycin In Patients With Glioblastoma Multiforme

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed intracranial glioblastoma multiforme

- Disease progression by MRI or CT scan

- Confirmation of true progressive disease (not radiation necrosis) by
positron-emission tomography, thallium scanning, MRI, or surgical documentation
required if patient received prior interstitial brachytherapy or stereotactic
radiosurgery

- Failed prior radiotherapy

- Phase I patients:

- Eligible for salvage surgery

- No limits on prior therapy

- Phase II patients:

- Tumor progression by MRI or CT scan required within the past 14 days if
recurrent disease is present

- No prior therapy for more than 3 relapses

- Recent resection of recurrent or progressive tumor allowed as long as all of the
following conditions apply:

- Recovered from surgery

- MRI or CT scan performed no more than 96 hours since prior surgery OR
within 4-6 weeks after surgery

- Baseline MRI or CT scan performed within 14 days of study entry

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Karnofsky 60-100%

Life expectancy

- More than 8 weeks

Hematopoietic

- WBC at least 3,000/mm^3

- Absolute neutrophil count at least 2,000/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 10 g/dL (transfusion allowed)

Hepatic

- Bilirubin less than 1.5 times upper limit of normal (ULN)

- SGOT less than 1.5 times ULN

Renal

- Creatinine less than 1.5 mg/dL

Other

- Cholesterol less than 350 mg/dL

- Triglycerides less than 400 mg/dL

- No concurrent disease that would obscure toxicity or dangerously alter drug
metabolism

- No other significant uncontrolled serious medical illness that would preclude study
participation

- No other cancer except non-melanoma skin cancer or carcinoma in situ of the cervix
unless patient is in complete remission and off all therapy for that disease for at
least 3 years

- No active infection

- No prior allergic reactions to compounds of similar chemical or biological
composition to sirolimus

- No psychiatric illness that would preclude study participation

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- At least 1 week since prior interferon

Chemotherapy

- At least 2 weeks since prior vincristine

- At least 3 weeks since prior procarbazine

- At least 6 weeks since prior nitrosoureas

Endocrine therapy

- At least 1 week since prior tamoxifen

Radiotherapy

- See Disease Characteristics

- At least 4 weeks since prior radiotherapy

Surgery

- See Disease Characteristics

Other

- Recovered from prior therapy

- At least 1 week since prior noncytotoxic agents (except radiosensitizers)