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Everolimus and Gefitinib in Treating Patients With Progressive Glioblastoma Multiforme or Progressive Metastatic Prostate Cancer

Study Purpose

RATIONALE: Everolimus may stop the growth of tumor cells by stopping blood flow to the tumor. Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining everolimus with gefitinib may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus when given together with gefitinib and to see how well they work in treating patients with progressive glioblastoma multiforme or (progressive metastatic prostate cancer closed to accrual 10/19/06).

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender Male
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT00085566
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Memorial Sloan Kettering Cancer Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Howard I. Scher, MDNeal Rosen, MDLauren E. Abrey, MD
Principal Investigator Affiliation Memorial Sloan Kettering Cancer CenterMemorial Sloan Kettering Cancer CenterMemorial Sloan Kettering Cancer Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, NIH
Overall Status Completed
Countries Spain, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Brain and Central Nervous System Tumors, Prostate Cancer
Additional Details

OBJECTIVES: Primary.

  • - Determine the maximum tolerated dose of everolimus when given in combination with gefitinib in patients with progressive glioblastoma multiforme or (progressive castrate metastatic prostate cancer -closed to accrual as of 10/19/2006).
(Phase I)
  • - Determine the safety and efficacy of this regimen in patients with progressive glioblastoma multiforme or (progressive castrate metastatic prostate cancer - closed to accrual as of 10/19/2006).
(Phase II) Secondary.
  • - Determine whether a pharmacokinetic interaction exists between everolimus and gefitinib in patients treated with this regimen.
  • - Determine the association between clinical outcomes and markers that may predict sensitivity of a tumor in patients treated with this regimen.
  • - Determine the pharmacodynamic effects of this regimen on post-therapy tumor specimens and peripheral blood mononuclear cells from these patients.
OUTLINE: This is a phase I, open-label, non-randomized, dose-escalation study of everolimus followed by a phase II study.
  • - 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.

Arms & Interventions

Arms

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.

Interventions

Drug: - everolimus

Drug: - gefitinib

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Memorial Sloan Kettering Cancer Center, New York, New York

Status

Address

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

International Sites

Vall d'Hebron University Hospital, Barcelona, Spain

Status

Address

Vall d'Hebron University Hospital

Barcelona, , 08035