Sirolimus Before Surgery in Treating Patients With Advanced Localized Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00311623
Recruitment Status : Unknown
Verified February 2009 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
First Posted : April 6, 2006
Last Update Posted : February 21, 2011
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as sirolimus, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This clinical trial is studying the best dose of sirolimus and to see how well it works before surgery in treating patients with advanced localized prostate cancer.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: sirolimus Other: immunohistochemistry staining method Procedure: neoadjuvant therapy Not Applicable

Detailed Description:



  • Determine the pharmacodynamically optimal dose (POD) of continuous daily oral sirolimus (rapamycin) in patients with advanced localized prostate cancer when given prior to radical prostatectomy, as measured by tumor S6 kinase inhibition by immunohistochemistry (IHC).
  • Determine the proportion of men with downstream target inhibition in prostate tumor tissue at the POD using paired tumor biopsies from before and after rapamycin administration.
  • Correlate tumor pharmacodynamic (PD) efficacy with a surrogate marker of tumor PD efficacy, peripheral blood mononuclear cell (PBMC) S6 kinase activity inhibition.


  • Characterize the serum and prostate tissue pharmacokinetics of daily oral rapamycin at 2 dose levels.
  • Determine the relationship of PD target inhibition of S6 kinase activity with pretreatment Akt activity and PTEN loss by IHC in prostate cancer.
  • Describe the relationship between PD inhibition with the mTOR inhibitor rapamycin and pretreatment prostate biopsy Gleason sum, Ki-67 index of proliferation, Akt activity, p27 IHC, and PTEN.
  • Correlate PD efficacy as measured by downstream S6 kinase activity inhibition with markers of increased apoptosis (activated caspase 3) and reduction in markers of proliferation (change in Ki-67) in prostate tumor specimens.
  • Quantify and characterize the toxicity of daily continuous rapamycin at 2 dose levels in generally healthy men with prostate cancer prior to surgery.
  • Evaluate the activity of rapamycin in prostate cancer as measured in prostate specific antigen response prior to surgery.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive oral sirolimus (rapamycin) once daily on days 1-14 in the absence of unacceptable toxicity.

Cohorts of 12-21 patients receive escalating doses of rapamycin until the pharmacodynamically optimal dose is determined.

Patients undergo radical prostatectomy on day 15.

Patients undergo blood collection and tumor biopsies periodically during study for pharmacologic and correlative biomarker studies.

After completion of study treatment, patients are followed at 30 and 90 days.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Primary Purpose: Treatment
Official Title: A Pharmacodynamic Study of Pre-Prostatectomy Rapamycin in Men With Advanced Localized Prostate Cancer
Study Start Date : August 2006
Estimated Primary Completion Date : January 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
U.S. FDA Resources

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No


  • Histologically determined adenocarcinoma of the prostate

    • Stage T1c-T3b disease
    • No evidence of disease that has spread beyond the prostate or seminal vesicles
  • No metastatic prostate cancer, including bone, visceral, brain, and lymph node metastases
  • Tumor Gleason score sum of 7-10 (4+3 and 3+4 allowed) with tumor involving at least 2 discrete core biopsy sections
  • Scheduled to undergo radical prostatectomy
  • No other subtypes of prostate cancer, including any of the following:

    • Sarcoma
    • Neuroendocrine tumors
    • Small cell cancer
    • Ductal cancer
    • Lymphoma


  • ECOG performance status 0-1
  • WBC > 3,500/mm^3
  • Absolute neutrophil count > 1,500/mm^3
  • Platelet count > 100,000/mm^3
  • Hemoglobin > 9 g/dL
  • Creatinine < 2.0 mg/dL
  • Bilirubin < 2 mg/dL
  • ALT and AST < 2 times upper limit of normal (ULN)
  • Alkaline phosphatase < 2 times ULN
  • Triglycerides and total cholesterol < 2 times ULN
  • No history of allergy to sirolimus (rapamycin) or its derivatives
  • No uncontrolled medical condition that would increase risk or limit compliance with study requirements, including the following:

    • Immunodeficiency
    • Gastrointestinal disease that would limit ability to swallow, take oral medications, or absorb them
  • No active infections
  • No other concurrent malignancy


  • See Disease Characteristics
  • No prior chemotherapy, biologic therapy, radiotherapy, or immunotherapy for prostate cancer
  • No concurrent chronic treatment with immunosuppressants or medications that interfere with the metabolism of sirolimus (rapamycin)
  • No concurrent medication or agents that would interfere with the metabolism or excretion of rapamycin or its derivatives, including any of the following:

    • Phenytoin
    • Carbamazepine
    • Cyclosporine
    • Clarithromycin
    • Clotrimazole
    • Erythromycin
    • Amiodarone
    • Protease inhibitors used to treated HIV infection
    • Cisapride
    • Grapefruit juice
    • Diltiazem
    • Tacrolimus
    • Hypericum perforatum (St. John's wort)
    • Barbiturates
    • Rifampin
    • Phenobarbital
    • Rifabutin
    • Efavirenz
    • Nevirapine
  • At least 7 days since prior herbal medicines and medications, including any of the following:

    • Hydrastis canadensis (goldenseal)
    • Uncaria tomentosa (cat's claw)
    • Echinacea angustifolia roots
    • Trifolium pretense (wild cherry)
    • Chamomile
    • Glycyrrhiza glabra (licorice)
    • Dillapiol
    • Naringenin
    • Norfloxacin
    • Atorvastatin
    • Pravastatin
    • Cimetidine
    • Fluconazole

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00311623

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0942
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Michael A. Carducci, MD Sidney Kimmel Comprehensive Cancer Center Identifier: NCT00311623     History of Changes
Other Study ID Numbers: CDR0000468942
First Posted: April 6, 2006    Key Record Dates
Last Update Posted: February 21, 2011
Last Verified: February 2009

Keywords provided by National Cancer Institute (NCI):
stage III prostate cancer
stage I prostate cancer
stage IIB prostate cancer
stage IIA prostate cancer
adenocarcinoma of the prostate

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs