Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant Prostate Cancer

NCT ID: NCT01020305

Last Updated: 2014-10-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2012-04-30

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.

Conditions

Prostate Cancer; Prostatic Neoplasms; Castrate-resistant Prostate Cancer (CRPC); Androgen-insensitive Prostate Cancer; Hormone-refractory Prostate Cancer; Metastatic Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Temsirolimus + Bicalutamide

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

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

Group Type: EXPERIMENTAL

Temsirolimus

Intervention Type: DRUG

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

Casodex (bicalutamide)

Intervention Type: DRUG

Casodex (bicalutamide) 50 mg/day PO

Interventions

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

Intervention Type: DRUG

Casodex (bicalutamide)

Casodex (bicalutamide) 50 mg/day PO

Intervention Type: DRUG

Other Intervention Names

Torisel; CCI-779; Casodex; bicalutamide; Cosudex; Calutide; Kalumid

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Wyeth is now a wholly owned subsidiary of Pfizer

INDUSTRY

Sponsor Role: collaborator

National Comprehensive Cancer Network

NETWORK

Sponsor Role: collaborator

American Society of Clinical Oncology

OTHER

Sponsor Role: collaborator

Sandy Srinivas

OTHER

Sponsor Role: lead

Responsible Party

Sandy Srinivas

Assoc Prof-Med Ctr Line

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Sandhya "Sandy" Srinivas, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Lauren Christine Harshman, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

Other Identifiers

NCT01020305

Identifier Type: OTHER

Identifier Source: secondary_id

SU-09292009-4080

Identifier Type: OTHER

Identifier Source: secondary_id

PROS0028

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-17242

Identifier Type: -

Identifier Source: org_study_id