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Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant Prostate Cancer

Primary Purpose

Prostate Cancer, Prostatic Neoplasms, Castrate-resistant Prostate Cancer (CRPC)

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Temsirolimus
Casodex (bicalutamide)
Sponsored by
Sandy Srinivas
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Stanford University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Temsirolimus + Bicalutamide

Arm Description

Temsirolimus 25 mg administered intravenously (IV) once weekly for 12 weeks Casodex (bicalutamide) administered 50 mg/day orally (PO)

Outcomes

Primary Outcome Measures

Reduction in Serum PSA
Proportion of subjects with > 50% drop in serum PSA as compared to baseline, assessed at 16 weeks

Secondary Outcome Measures

Full Information

First Posted
October 30, 2009
Last Updated
October 3, 2014
Sponsor
Sandy Srinivas
Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer, National Comprehensive Cancer Network, American Society of Clinical Oncology
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1. Study Identification

Unique Protocol Identification Number
NCT01020305
Brief Title
Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant Prostate Cancer
Official Title
Temsirolimus, an mTOR Inhibitor, to Reverse Androgen Insensitivity in Patients With Castration-resistant Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2014
Overall Recruitment Status
Terminated
Why Stopped
Decision by funding sponsor due to poor accrual
Study Start Date
October 2009 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Sandy Srinivas
Collaborators
Wyeth is now a wholly owned subsidiary of Pfizer, National Comprehensive Cancer Network, American Society of Clinical Oncology

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer, Prostatic Neoplasms, Castrate-resistant Prostate Cancer (CRPC), Androgen-insensitive Prostate Cancer, Hormone-refractory Prostate Cancer, Metastatic Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Temsirolimus + Bicalutamide
Arm Type
Experimental
Arm Description
Temsirolimus 25 mg administered intravenously (IV) once weekly for 12 weeks Casodex (bicalutamide) administered 50 mg/day orally (PO)
Intervention Type
Drug
Intervention Name(s)
Temsirolimus
Other Intervention Name(s)
Torisel, CCI-779
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Casodex (bicalutamide)
Other Intervention Name(s)
Casodex, bicalutamide, Cosudex, Calutide, Kalumid
Intervention Description
Casodex (bicalutamide) 50 mg/day PO
Primary Outcome Measure Information:
Title
Reduction in Serum PSA
Description
Proportion of subjects with > 50% drop in serum PSA as compared to baseline, assessed at 16 weeks
Time Frame
12 weeks treatment, with primary outcome assessed at 16 weeks

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sandhya "Sandy" Srinivas, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lauren Christine Harshman, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant Prostate Cancer

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