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Trial record 1 of 1 for:    NCT01020305
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Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant 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: NCT01020305
Recruitment Status : Terminated (Decision by funding sponsor due to poor accrual)
First Posted : November 25, 2009
Results First Posted : October 13, 2014
Last Update Posted : October 13, 2014
Wyeth is now a wholly owned subsidiary of Pfizer
National Comprehensive Cancer Network
American Society of Clinical Oncology
Information provided by (Responsible Party):
Sandy Srinivas, Stanford University

Tracking Information
First Submitted Date  ICMJE October 30, 2009
First Posted Date  ICMJE November 25, 2009
Results First Submitted Date  ICMJE October 3, 2014
Results First Posted Date  ICMJE October 13, 2014
Last Update Posted Date October 13, 2014
Study Start Date  ICMJE October 2009
Actual Primary Completion Date April 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 3, 2014)
Reduction in Serum PSA [ Time Frame: 12 weeks treatment, with primary outcome assessed at 16 weeks ]
Proportion of subjects with > 50% drop in serum PSA as compared to baseline, assessed at 16 weeks
Original Primary Outcome Measures  ICMJE
 (submitted: November 20, 2009)
PSA response at 13 weeks since Day 1 dosing. PSA response is defined as a decrease >=50% from baseline [ Time Frame: 13 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2009)
  • Safety, Tolerability as defined by the percent of patients who discontinue due to toxicity, Time to PSA Progression, Median number of CTCs pre- and post-therapy, Characterization of pre- and post-therapy CTCs [ Time Frame: 42 days of last Temsirolimis dose Outcome ]
  • Time TO PSA progression end point [ Time Frame: within in 1 year of last study Temsirolimus ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant Prostate Cancer
Official Title  ICMJE Temsirolimus, an mTOR Inhibitor, to Reverse Androgen Insensitivity in Patients With Castration-resistant Prostate Cancer
Brief Summary This study evaluates if temsirolimus causes a reduction in the serum levels of prostate-specific antigen (PSA) in male subjects with castration-resistant prostate cancer (CRPC).
Detailed Description

Castration-resistant prostate cancer (CRPC) is also known as "androgen-insensitive" or "hormone-refractory" prostate cancer. While numerous therapies impact biochemical response in the setting of CRPC, there remains unmet medical need. New therapies that extend survival of patients beyond that provided by chemotherapy are needed.

The mechanisms of tumor progression to castration-resistance are unclear, but preclinical studies suggest that functional loss of the tumor suppressor gene PTEN and subsequent up-regulation of Akt, which is upstream of mTOR, may be involved in prostate cancer progression and metastasis. Based on these observations, it is hypothesized that mTOR inhibitor temsirolimus may prolong hormone sensitivity and delay disease progression in castration-resistant prostate cancer patients before antiandrogen withdrawal.

This study will assess efficacy on the basis of serum levels of PSA, an established surrogate endpoint for efficacy in prostate cancer.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Prostate Cancer
  • Prostatic Neoplasms
  • Castrate-resistant Prostate Cancer (CRPC)
  • Androgen-insensitive Prostate Cancer
  • Hormone-refractory Prostate Cancer
  • Metastatic Disease
Intervention  ICMJE
  • Drug: Temsirolimus

    Temsirolimus is an inhibitor of the mammalian target of rapamycin (MTOR, aka HGNC:3942)

    IUPAC name: (1R,2R,4S)-4-{(2R)-2-[(3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-1,5,11,28,29-pentaoxo-1,4,5,6,9,10,11,12,13,14,21,22,23,24,25,26,27,28,29,31,32,33,34,34a-tetracosahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontin-3-yl]propyl}-2-methoxycyclohexyl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate

    Other Names:
    • Torisel
    • CCI-779
  • Drug: Casodex (bicalutamide)
    Casodex (bicalutamide) 50 mg/day PO
    Other Names:
    • Casodex
    • bicalutamide
    • Cosudex
    • Calutide
    • Kalumid
Study Arms  ICMJE Experimental: Temsirolimus + Bicalutamide

Temsirolimus 25 mg administered intravenously (IV) once weekly for 12 weeks

Casodex (bicalutamide) administered 50 mg/day orally (PO)

  • Drug: Temsirolimus
  • Drug: Casodex (bicalutamide)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 13, 2012)
Original Estimated Enrollment  ICMJE
 (submitted: November 20, 2009)
Actual Study Completion Date  ICMJE April 2012
Actual Primary Completion Date April 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE


  • Histologically-confirmed adenocarcinoma of the prostate, characterized as symptomatic castration-resistant prostate cancer (CRPC)
  • Serum PSA ≥ 2 ng/mL
  • Rising PSA on 3 consecutive occasions at least 1 week apart (not limited to the 30-day screening period)
  • Failure of bilateral orchiectomy and/or therapy with an LHRH agonist and bicalutamide
  • Castrate level of testosterone (< 50 ng/dL)
  • Currently being treated with bicalutamide
  • No prior antiandrogen therapy except bicalutamide
  • Age ≥ 18 years
  • Life expectancy > 6 months
  • Performance status

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
    • OR
    • Karnofsky performance status ≥ 80%
  • Ability to understand and the willingness to sign a written informed consent


  • Radiotherapy for prostate cancer within 28 days prior to Day 1, except single-fraction radiotherapy for pain control
  • Prior treatment with mTOR inhibitors
  • Prior treatment with chemotherapy for prostate cancer
  • Symptomatic bone metastases (ie, asymptomatic bone metastases are eligible)
  • Visceral metastases
  • Absolute neutrophil count (ANC) < 1500/uL
  • Platelet count ≤ 100 x 10e9/L
  • Total bilirubin ≥ 1.5 x Upper Limit of Normal (ULN)
  • Alkaline phosphatase > 2.5 x ULN
  • AST > 2.5 x ULN
  • ALT > 2. 5x ULN
  • Serum creatinine > 2.0 mg/dL
  • Hemoglobin < 9 g/dL
  • Men with reproductive potential who do not agree to use an accepted and effective method of contraception during the study treatment period and for at least 3 months after completion of the study treatment
  • History of other malignancies within 5 years except for tumors with a negligible risk for metastasis or death, such as adequately-controlled basal cell carcinoma, squamous-cell carcinoma of the skin, or early-stage bladder cancer
  • Participation in another experimental drug study either planned or within 4 weeks of the first study treatment
  • Persistent Grade ≥ 1 AEs due to prior drug therapy, including investigational drugs, administered more than 14 days before study enrollment
  • Previously treated or other known brain metastases
  • Ongoing or active infection
  • Symptomatic congestive heart failure, New York Heart Association Grade II or greater
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Significant vascular disease (eg, aortic aneurysm, aortic dissection)
  • Symptomatic peripheral vascular disease
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Other uncontrolled intercurrent illness
  • Known to be positive for the human immunodeficiency virus (HIV) infection and receiving antiretroviral therapies (HIV positive not requiring antiretroviral therapy iseligible if all other entry criteria are meet)
  • Inability to comply with study and/or follow-up procedures
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01020305
Other Study ID Numbers  ICMJE IRB-17242
SU-09292009-4080 ( Other Identifier: Stanford University )
PROS0028 ( Other Identifier: OnCore )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sandy Srinivas, Stanford University
Study Sponsor  ICMJE Sandy Srinivas
Collaborators  ICMJE
  • Wyeth is now a wholly owned subsidiary of Pfizer
  • National Comprehensive Cancer Network
  • American Society of Clinical Oncology
Investigators  ICMJE
Principal Investigator: Sandhya "Sandy" Srinivas, MD Stanford University
Principal Investigator: Lauren Christine Harshman, MD Stanford University
PRS Account Stanford University
Verification Date October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP