Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant Prostate Cancer

• Status: Terminated
• Trial end date: 2012-04-01
• Target enrollment: 0
• Participant gender: Male

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).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sandy Srinivas
• Collaborators: American Society of Clinical Oncology; National Comprehensive Cancer Network; Wyeth is now a wholly owned subsidiary of Pfizer
• Treatments: Androgens; Bicalutamide; Everolimus; Sirolimus

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