Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant Prostate Cancer

This study has been terminated.
National Comprehensive Cancer Network
Wyeth is now a wholly owned subsidiary of Pfizer
American Society of Clinical Oncology
Information provided by (Responsible Party):
Sandy Srinivas, Stanford University
ClinicalTrials.gov Identifier:
First received: October 30, 2009
Last updated: July 13, 2012
Last verified: July 2012

October 30, 2009
July 13, 2012
October 2009
April 2012   (final data collection date for primary outcome measure)
PSA response at 13 weeks since Day 1 dosing. PSA response is defined as a decrease >=50% from baseline [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01020305 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: Yes ]
  • Time TO PSA progression end point [ Time Frame: within in 1 year of last study Temsirolimus ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant Prostate Cancer
Temsirolimus, an mTOR Inhibitor, to Reverse Androgen Insensitivity in Patients With Castration-resistant Prostate Cancer

There is a clear need for novel effective agents in castration-resistant prostate cancer (CRPC), an entity previously referred to as "androgen-insensitive" or "hormone-refractory" prostate cancer. While numerous therapies impact biochemical response in this disease, none improve overall survival outside of chemotherapy. The mechanisms behind progression to castration-resistance are unclear, but preclinical studies suggest that 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, we hypothesize that inhibition of mTOR activity with an IV mTOR inhibitor, temsirolimus, may prolong hormone sensitivity and delay disease progression. We have received approval and drug support from the NCCN and Wyeth to study temsirolimus in castration-resistant prostate cancer before antiandrogen withdrawal in a phase II, single stage, non-randomized clinical trial. Forty patients who are currently on combined androgen blockade with bicalutamide, who have evidence of disease progression by PSA or bony metastasis will receive temsirolimus weekly for 13 weeks. Because evaluating new therapies in prostate cancer is uniquely challenging given its long natural history and relatively indolent nature, this study will employ an established surrogate endpoint for efficacy, prostate-specific antigen (PSA), which will permit preliminary evaluation of this combination in fewer patients and in less time than would otherwise be possible in this disease, and additionally evaluates secondary time-to-event outcomes. By co-targeting the androgen and PTEN/Akt/mTOR signaling pathways in castration-resistant prostate cancer, we see great potential to impact this pervasive disease.

Not Provided
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Prostatic Neoplasms
  • Prostate Cancer
  • Prostate Cancer Localized Disease
Drug: Temsirolimus
25mg intravenously (IV) once weekly for 12 weeks
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
April 2012
April 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:- Histologically confirmed adenocarcinoma of the prostate

  • Patients with asymptomatic CRPC. To be considered castration-resistant requires the following 3 criteria:

    • Failure of bilateral orchiectomy or therapy with an LHRH agonist and bicalutamide
    • A rising PSA on 3 consecutive occasions at least 1 week apart (but not limited to the 30 day screening period), AND
    • A castrate level of testosterone (<50ng/dL)
  • Currently being treated with bicalutamide
  • No prior antiandrogen therapy except bicalutamide
  • A minimum PSA of 2 ng/mL
  • Age >= 18 years
  • Life expectancy greater than 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or Karnofsky performance status >= 80%
  • Asymptomatic bone metastases will be allowed
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:- Radiotherapy for prostate cancer within 28 days prior to Day 1, with the exception of single-fraction radiotherapy given for the indication of pain control

  • Prior treatment with mTOR inhibitors
  • Prior treatment with chemotherapy for prostate cancer
  • Symptomatic bone metastases
  • Visceral metastases
  • Inadequate organ function, as evidenced by any of the following at screening:

    • Absolute neutrophil count (ANC) < 1500/uL
    • Platelet count <= 100 x 10^9/L
    • Total bilirubin >= 1.5 x ULN
    • Alkaline phosphatase, AST, and/or 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 prior to Day 1 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
  • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study.
  • Persistent Grade >=1 (NCI CTCAE v3.0) AEs due to investigational drugs or other medications that were administered more than 14 days before study enrollment.
  • Known or prior treated brain metastases. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (defined as New York Heart Association Grade II or greater, see Appendix A), unstable angina pectoris, cardiac arrhythmia, significant vascular disease (e.g. aortic aneurysm, aortic dissection), symptomatic peripheral vascular disease, or psychiatric illness/social situations that would limit compliance with study requirements.
  • The subject is known to be positive for the human immunodeficiency virus (HIV) and is receiving antiretroviral therapies. Subjects known to be HIV positive who do not require antiretroviral therapy will be eligible if they meet other entry criteria.
  • Inability to comply with study and/or follow-up procedures
18 Years and older
Contact information is only displayed when the study is recruiting subjects
United States
PROS0028, SU-09292009-4080
Not Provided
Sandy Srinivas, Stanford University
Sandy Srinivas
  • National Comprehensive Cancer Network
  • Wyeth is now a wholly owned subsidiary of Pfizer
  • American Society of Clinical Oncology
Principal Investigator: Dr. Sandy Srinivas Stanford University
Principal Investigator: Lauren Harshman Stanford University
Stanford University
July 2012

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