Temsirolimus and Vorinostat in Treating Patients With Metastatic Prostate Cancer

Phase 1

Terminated

• Conditions: Adenocarcinoma of the Prostate; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage IV Prostate Cancer; Prostate Cancer
• Interventions: Drug: vorinostat; Drug: temsirolimus; Other: laboratory biomarker analysis; Procedure: positron emission tomography/computed tomography

• Registration Number: NCT01174199
• Lead Sponsor: Roswell Park Cancer Institute

Brief Summary

RATIONALE: Temsirolimus and vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving temsirolimus together with vorinostat may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of temsirolimus and vorinostat in treating patients with metastatic prostate cancer.

Detailed Description

PRIMARY OBJECTIVES: I. To determine the safety, tolerability and recommended Phase II dose of temsirolimus in combination with vorinostat in patients with metastatic, hormone refractory, chemoresistant prostate cancer. II. To obtain preliminary evidence of response in prostate cancer patients treated with temsirolimus and vorinostat. SECONDARY OBJECTIVES: I. To determine the partial and complete objective response rates in metastatic hormone-refractory, chemo-resistant prostate cancer patients with measurable disease treated with temsirolimus and vorinostat. II. To determine the progression free survival and overall survival in patients with metastatic hormone refractory, chemo-resistant prostate cancer. III. To determine the PSA response, the duration of PSA response, time to PSA progression, PSA doubling time and PSA slope in metastatic hormone refractory, chemo-resistant prostate cancer patients treated with temsirolimus and vorinostat. IV. To assess changes in expression levels of bone remodeling markers (N telopeptides and bone alkaline phosphatase) and angiogenesis-related gene and protein expression (VEGF/HIF1-alpha) in blood and circulating tumor cells, and when available, in tissue, and correlate them with cancer and treatment related outcomes. V. To assess the changes in tumor metabolism with FDG/IIC-Choline PET/CT scan. OUTLINE: Patients receive oral vorinostat once daily on days 1-14 and temsirolimus IV on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 30 days and then every 3 months thereafter.

Study Timeline

• Study First Submitted: 2010-07-30
• Study First Submitted QC: 2010-08-02
• Study First Posted: 2010-08-03
• Study Start: 2012-02
• Primary Completion: 2015-08
• Study Completion: 2016-08
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-30
• Last Update Posted: 2022-10-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 13

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	laboratory biomarker analysis	Patients receive oral vorinostat once daily on days 1-14 and temsirolimus IV on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Arm I	positron emission tomography/computed tomography	Patients receive oral vorinostat once daily on days 1-14 and temsirolimus IV on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Arm I	vorinostat	Patients receive oral vorinostat once daily on days 1-14 and temsirolimus IV on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Arm I	temsirolimus	Patients receive oral vorinostat once daily on days 1-14 and temsirolimus IV on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Frequencies of DLT and toxicity	4 yrs
Adverse events	4 years

Secondary Outcome Measures

Name	Time	Method
Median survival, median progression-free survival, and frequency of deaths	4 years
Changes in tumor metabolism as assessed by PET/CT scan	Prior to each cycle
PSA response	Every 2 cycles of treatment
Changes in expression of bone remodeling markers and angiogenesis-related gene and protein expression	Prior to each cycle

Trial Locations

Locations (2)

The Sydney Kimmel Comprehensive Center at John Hopkins; 🇺🇸 Baltimore, Maryland, United States

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States