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An Open-Label Study Of Exploratory Pharmacogenomics And Pharmacologic Effects Of Neoadjuvant Oral CCI-779 In Newly Diagnosed Prostate Cancer Patients Undergoing Radical Prostatectomy Who Have A High Risk Of Relapse


Phase 2
18 Years
N/A
Not Enrolling
Male
Prostate Cancer

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Trial Information

An Open-Label Study Of Exploratory Pharmacogenomics And Pharmacologic Effects Of Neoadjuvant Oral CCI-779 In Newly Diagnosed Prostate Cancer Patients Undergoing Radical Prostatectomy Who Have A High Risk Of Relapse


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phosphorylation state of proteins

Safety Issue:

No

Principal Investigator

Charles Sawyers, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Jonsson Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000331979

NCT ID:

NCT00071968

Start Date:

August 2003

Completion Date:

Related Keywords:

  • Prostate Cancer
  • adenocarcinoma of the prostate
  • stage IIB prostate cancer
  • stage IIA prostate cancer
  • stage I prostate cancer
  • Prostatic Neoplasms

Name

Location

Jonsson Comprehensive Cancer Center at UCLALos Angeles, California  90095-1781