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Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant Prostate Cancer

This study has been terminated.
(Decision by funding sponsor due to poor accrual)
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
ClinicalTrials.gov Identifier:
NCT01020305
First received: October 30, 2009
Last updated: October 3, 2014
Last verified: October 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Temsirolimus, an mTOR Inhibitor, to Reverse Androgen Insensitivity in Patients With Castration-resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Reduction in Serum PSA [ Time Frame: 12 weeks treatment, with primary outcome assessed at 16 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with > 50% drop in serum PSA as compared to baseline, assessed at 16 weeks


Enrollment: 5
Study Start Date: October 2009
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01020305

Locations
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
Principal Investigator: Sandhya "Sandy" Srinivas, MD Stanford University
Principal Investigator: Lauren Christine Harshman, MD Stanford University
  More Information

No publications provided

Responsible Party: Sandy Srinivas, Assoc Prof-Med Ctr Line, Stanford University
ClinicalTrials.gov Identifier: NCT01020305     History of Changes
Other Study ID Numbers: IRB-17242, SU-09292009-4080, PROS0028
Study First Received: October 30, 2009
Results First Received: October 3, 2014
Last Updated: October 3, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Neoplasm Metastasis
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Prostatic Diseases
Urogenital Neoplasms
Androgens
Bicalutamide
Everolimus
Sirolimus
Androgen Antagonists
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Hormone Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014