Temsirolimus to Reverse Androgen Insensitivity for Castration-resistant Prostate Cancer

NCT01020305 | Terminated Phase 1 Results DMC

• 4 other identifiers: IRB-17242NCT01020305SU-09292009-4080PROS0028
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Reduction in Serum PSA

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

  12 weeks treatment, with primary outcome assessed at 16 weeks

Study Arms (1)

Temsirolimus + Bicalutamide

EXPERIMENTAL

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

Drug: Temsirolimus; Drug: Casodex (bicalutamide)

Interventions

Temsirolimus 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

Also known as: Torisel, CCI-779

Temsirolimus + Bicalutamide

Casodex (bicalutamide) DRUG

Casodex (bicalutamide) 50 mg/day PO

Also known as: Casodex, bicalutamide, Cosudex, Calutide, Kalumid

Temsirolimus + Bicalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Karnofsky performance status ≥ 80%
• Ability to understand and the willingness to sign a written informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Sandy Srinivas: lead
• Wyeth is now a wholly owned subsidiary of Pfizer: collaborator
• National Comprehensive Cancer Network: collaborator
• American Society of Clinical Oncology: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Interventions

temsirolimus; bicalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Associate Professor of Medicine (Oncology)
• Organization: Stanford University Medical Center

sandysri@stanford.edu

650-725-2078

Study Officials

• Sandhya "Sandy" Srinivas, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Lauren Christine Harshman, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assoc Prof-Med Ctr Line

Study Record Dates

• First Submitted: October 30, 2009
• First Posted: November 25, 2009
• Study Start: October 1, 2009
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: October 13, 2014
• Results First Posted: October 13, 2014

Record last verified: 2014-10

Locations

US (1)