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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.
 
ClinicalTrials.gov 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
Sponsor:
Collaborators:
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

Study Description
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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).

Condition or disease Intervention/treatment Phase
Prostate Cancer Prostatic Neoplasms Castrate-resistant Prostate Cancer (CRPC) Androgen-insensitive Prostate Cancer Hormone-refractory Prostate Cancer Metastatic Disease Drug: Temsirolimus Drug: Casodex (bicalutamide) Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Temsirolimus, an mTOR Inhibitor, to Reverse Androgen Insensitivity in Patients With Castration-resistant Prostate Cancer
Study Start Date : October 2009
Actual Primary Completion Date : April 2012
Actual Study Completion Date : April 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Temsirolimus + Bicalutamide

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

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

 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


Outcome Measures
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Primary Outcome Measures :
  1. 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


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

INCLUSION CRITERIA

  • 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

EXCLUSION CRITERIA

  • 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
Contacts and Locations
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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 ClinicalTrials.gov identifier (NCT number): NCT01020305


Locations
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United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Sandy Srinivas
Wyeth is now a wholly owned subsidiary of Pfizer
National Comprehensive Cancer Network
American Society of Clinical Oncology
Investigators
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Principal Investigator: Sandhya "Sandy" Srinivas, MD Stanford University
Principal Investigator: Lauren Christine Harshman, MD Stanford University
More Information
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Responsible Party: Sandy Srinivas, Assoc Prof-Med Ctr Line, Stanford University
ClinicalTrials.gov Identifier: NCT01020305    
Other Study ID Numbers: IRB-17242
SU-09292009-4080 ( Other Identifier: Stanford University )
PROS0028 ( Other Identifier: OnCore )
First Posted: November 25, 2009    Key Record Dates
Results First Posted: October 13, 2014
Last Update Posted: October 13, 2014
Last Verified: October 2014
Additional relevant MeSH terms:
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Prostatic Neoplasms
Prostatic Diseases
Sirolimus
Temsirolimus
MTOR Inhibitors
Neoplasm Metastasis
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Genital Diseases
Urogenital Diseases
Male Urogenital Diseases
Neoplastic Processes
 Pathologic Processes
Bicalutamide
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Androgen Antagonists
Hormone Antagonists