Everolimus and Gefitinib in Treating Patients With Progressive Glioblastoma Multiforme or Progressive Metastatic Prostate Cancer
Brain and Central Nervous System Tumors, Prostate Cancer
About this trial
This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring adult glioblastoma, recurrent prostate cancer, recurrent adult brain tumor, stage IV prostate cancer, adult giant cell glioblastoma, adult gliosarcoma
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of 1 of the following: Glioblastoma multiforme (GBM) (phase I only) Progressive disease despite standard therapy Progressive disease based on 1 of the following: New or progressive (25% bidimensional increase) soft tissue masses on CT scan or MRI New or prior lesions that have increased in size by physical examination Patients who had prior interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true disease progression (rather than radiation necrosis) by positron-emission tomography scan, thallium scanning, magnetic resonance spectroscopy, or surgical documentation Castrate metastatic prostate cancer (closed to accrual as of 10/19/2006) (phase I and II) Progressive disease despite standard therapy AND castrate levels < 50 ng/dL of testosterone Progressive disease based on 1 or more of the following: A minimum of 3 rising levels of prostate-specific antigen (PSA) that are obtained 1 or more weeks apart OR 2 rising PSA values obtained more than 1 month apart with at least a 25% increase over the range of values New or progressive (25% bidimensional increase) soft tissue masses on CT scan or MRI New metastatic lesions Patients on an antiandrogen as part of initial therapy must show disease progression after discontinuation of the antiandrogen Patients who have not undergone surgical orchiectomy must continue with medical therapy (e.g., gonadotropin-releasing hormone analogs) to maintain castrate levels of serum testosterone No brain metastases PATIENT CHARACTERISTICS: Age Over 18 Performance status Karnofsky 70-100% Life expectancy More than 3 months Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 WBC ≥ 3,000/mm^3 Hepatic ALT and AST ≤ 2.5 times upper limit of normal (ULN) Bilirubin ≤ 1.5 mg/dL Renal Creatinine within 1.5 times ULN (< 1.95 mg/dL at MSKCC) Cardiovascular No significant cardiovascular disease No congestive heart failure No New York Heart Association class III or IV cardiac disease No active angina pectoris No myocardial infarction within the past 6 months Other Not pregnant Negative pregnancy test Fertile patients must use effective contraception No serious medical illness No severe infection No severe malnutrition No other active malignancy except non-melanoma skin cancer Patients are not considered to have an active malignancy if they have completed prior therapy and currently have a < 30% risk for relapse PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent biological therapy No concurrent immunotherapy Chemotherapy No concurrent chemotherapy Endocrine therapy See Disease Characteristics Radiotherapy See Disease Characteristics More than 4 weeks since prior radiotherapy No concurrent radiotherapy Surgery See Disease Characteristics Prior recent resection of recurrent or progressive GBM allowed provided patient has recovered More than 4 weeks since prior major surgery Other Recovered from all prior therapy More than 4 weeks since prior investigational anticancer drugs No concurrent anticonvulsant that interacts with CYP3A4 (e.g., phenytoin, carbamazepine, or phenobarbital) No other concurrent cytotoxic therapy No other concurrent investigational or commercial agents or therapies for the malignancy
Sites / Locations
- Memorial Sloan Kettering Cancer Center
- Vall d'Hebron University Hospital
Arms of the Study
Arm 1
Experimental
Everolimus (RAD-001) and Gefitinib
•Phase I: Patients receive oral everolimus on day 1 and oral gefitinib once daily on days 8-21. Beginning on day 22, patients receive oral everolimus once weekly and oral gefitinib once daily. Treatment with the combination continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. •Phase II (prostate cancer patients only) (closed to accrual as of 10/19/2006): Patients receive oral everolimus (at the MTD determined in phase I) once weekly and oral gefitinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.