Prostate Cancer Clinical Trial
Neoadjuvant CCI-779 Followed By Radical Prostatectomy in Treating Patients With Newly Diagnosed Prostate Cancer Who Have a High Risk of Relapse
Summary
RATIONALE: Drugs used in chemotherapy, such as CCI-779, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving CCI-779 before surgery may shrink the tumor so that it can be removed.
PURPOSE: This randomized phase II trial is studying how well CCI-779 works in treating patients who are undergoing radical prostatectomy for newly diagnosed prostate cancer at high risk of relapse.
Full Description
OBJECTIVES:
Primary
Determine the effects of oral CCI-779 on changes in the phosphorylation state of proteins in the mammalian target of rapamycin (mTOR) signaling pathway in the tumor tissue of patients with newly diagnosed prostate cancer undergoing radical prostatectomy.
Determine the effects of this drug on changes in p70S6 kinase activity, phosphorylation state of mTOR pathway proteins, and on global and targeted gene expression patterns in the peripheral blood mononuclear cells (PBMCs) of these patients.
Secondary
Determine the effects of this drug on global and targeted gene expression patterns in these patients.
Identify pharmacodynamic/pharmacogenomic surrogate markers of this drug in both tumor tissue and PBMCs and determine if blood may be used as a surrogate tissue source for biomarkers of drug activity in the tumor in these patients.
Determine, preliminarily, the potential antitumor effects of this drug in these patients.
Determine the pharmacokinetics of this drug in these patients.
Correlate phosphatase and tensin homolog (PTEN) gene status with the pharmacodynamic/pharmacogenomic effects of this drug in these patients.
Determine the effects of this drug on changes in protein expression patterns in the plasma of these patients.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 3 treatment arms. Patients randomized to arm III are stratified according to tumor expression of phosphatase and tensin homolog (PTEN) gene mutations (negative vs positive).
Arm I: Patients receive oral CCI-779 once daily for a total of 8 weeks.
Arm II: Patients receive a higher dose of CCI-779 as in arm I.
Arm III: Patients receive a higher dose (higher than arm II) of CCI-779 as in arm I.
Approximately 24-48 hours after the last dose of CCI-779, patients in all arms undergo radical prostatectomy.
Patients are followed on day 7-10 and then at 4 weeks after study completion.
PROJECTED ACCRUAL: A total of 40 patients (5 each for arms I and II and 30 for arm III) will be accrued for this study.
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically confirmed adenocarcinoma of the prostate
Diagnosis based on a minimum of 6 core biopsy samples
Clinically confirmed organ-confined disease
Candidate for radical prostatectomy
No evidence of metastatic disease by CT scan and bone scan
High risk of relapse based on either of the following criteria:
Any one of the following:
Stage T2C or higher
Gleason score greater than 7
Prostate-specific antigen (PSA) greater than 20 ng/mL OR
Any two of the following:
Gleason score at least 7
PSA 10-20 ng/mL
Greater than 50% of total biopsy cores with cancer involvement
PATIENT CHARACTERISTICS:
Age
18 and over
Performance status
ECOG 0-1
Life expectancy
Not specified
Hematopoietic
No active bleeding
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 10 g/dL
Hepatic
No acute or chronic hepatitis B
Hepatitis B surface antigen negative
No acute or chronic hepatitis C
No antibodies to hepatitis C
Bilirubin no greater than 1.5 times upper limit of normal (ULN)
AST and ALT no greater than 2 times ULN
Renal
No ongoing urinary tract infection necessitating rapid or emergent surgical resection
Creatinine no greater than 1.5 times ULN
Cardiovascular
No unstable angina
No myocardial infarction within the past 6 months
No life-threatening ventricular arrhythmia requiring ongoing maintenance therapy
Pulmonary
No known pulmonary hypertension
No pneumonitis
Other
Fertile patients must use effective contraception during and for 12 weeks after study participation
HIV negative
No other severe immunocompromised states
No active infection requiring antibiotic therapy
No serious concurrent illness
No other major illness that would substantially increase the risk associated with study participation
No other malignancy within the past 5 years except basal cell or squamous cell skin cancer
PRIOR CONCURRENT THERAPY:
Biologic therapy
No concurrent immunotherapy
Chemotherapy
No prior chemotherapy
No other concurrent chemotherapy
Endocrine therapy
More than 3 weeks since prior IV corticosteroids
No concurrent systemic corticosteroids
No prior or concurrent hormonal therapy for underlying malignancy
Radiotherapy
No prior or concurrent radiotherapy
Surgery
More than 3 months since prior major surgery
Other
More than 1 month since prior experimental drugs
More than 3 weeks since prior immunosuppressive agents
No concurrent immunosuppressive therapies
No other concurrent investigational agents
No concurrent enzyme-inducing anticonvulsants (e.g., phenobarbital, phenytoin, or carbamazepine)
No concurrent ketoconazole, diltiazem, rifampin, terfenadine, cisapride, astemizole, pimozide, or Hypericum perforatum (St. John's wort)
No concurrent grapefruit or grapefruit juice
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There is 1 Location for this study
Los Angeles California, 90095, United States
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