Phase I/II Study of OSI-774 (Erlotinib) and CCI-779 (Temsirolimus) in Patients With Recurrent Malignant Glioma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed intracranial malignant glioma of 1 of the following types:

- Glioblastoma multiforme

- Gliosarcoma

- Anaplastic astrocytoma

- Anaplastic oligodendroglioma

- Anaplastic mixed oligoastrocytoma

- Malignant astrocytoma not otherwise specified

- Prior low-grade glioma allowed provided a subsequent histological diagnosis of
high-grade malignant glioma has been made

- Unequivocal evidence of progressive disease by MRI or CT scan while on a stable dose
of steroids for ≥ 5 days

- Stable dose of steroids prior to MRI or CT scan is not required for patients
enrolled in the preoperative component of the phase II study

- Failed prior radiotherapy

- Meets 1 of the following criteria for treatment of prior relapses:

- Treatment for any number of prior relapses allowed (phase I patients only)

- Treated for no more than 2 prior relapses* (phase II patients only)

- Prior surgical resection for relapsed disease with no anticancer therapy
for up to 12 weeks followed by another surgical resection is considered 1
relapse

- Prior therapy for low-grade glioma followed by surgical diagnosis of
high-grade glioma is considered 1 relapse NOTE: *No more than 3 prior
therapies, including initial treatment and treatment for 2 relapses

- Unstained slides or paraffin tissue block available from ≥ 1 prior surgery (phase II)

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Karnofsky 60-100%

Life expectancy

- More than 8 weeks

Hematopoietic

- WBC ≥ 2,000/mm^3

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

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 10 g/dL (transfusion allowed)

Hepatic

- SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN)

- Total bilirubin normal

Renal

- Creatinine < 1.5 mg/dL

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception during and for 3 months
after completion of study treatment

- Cholesterol ≤ 350 mg/dL

- Triglycerides ≤ 400 mg/dL

- No other malignancy except nonmelanoma skin cancer, carcinoma in situ of the cervix,
or cancer in complete remission that has not been treated within the past 3 years

- No active infection

- No serious medical illness

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

- No significant uncontrolled medical illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- At least 1 week since prior interferon or thalidomide

- No concurrent prophylactic filgrastim (G-CSF)

- No concurrent anticancer immunotherapy

Chemotherapy

- At least 2 weeks since prior vincristine

- At least 6 weeks since prior nitrosoureas

- At least 3 weeks since prior procarbazine

- No prior temsirolimus

- No other concurrent anticancer chemotherapy

Endocrine therapy

- See Disease Characteristics

- At least 1 week since prior tamoxifen

- No concurrent anticancer hormonal therapy

Radiotherapy

- See Disease Characteristics

- At least 6 weeks since prior radiotherapy

- Prior interstitial brachytherapy or stereotactic radiosurgery allowed provided there
is evidence of true progressive disease (rather than radiation necrosis) by positron
emission tomography or thallium scan, MR spectroscopy, or surgical documentation of
disease

- No concurrent anticancer radiotherapy

Surgery

- See Disease Characteristics

- Prior resection of recurrent or progressive disease allowed provided patient has
recovered

- Residual disease after tumor resection is not required

Other

- Recovered from all prior therapy

- At least 4 weeks since prior investigational agents

- At least 4 weeks since prior cytotoxic therapy

- At least 1 week since prior non-cytotoxic therapy (e.g., interferon, tamoxifen,
thalidomide, isotretinoin, etc.) except radiosensitizers

- At least 2 weeks since prior and no concurrent enzyme-inducing anti-epileptic drugs

- No prior erlotinib

- No other prior mTOR or epidermal growth factor receptor inhibitors

- No concurrent antiretroviral therapy for HIV-positive patients

- No other concurrent investigational drugs

- No other concurrent anticancer therapy