Temsirolimus and Bevacizumab in Hormone-Resistant Metastatic Prostate Cancer That Did Not Respond to Chemotherapy

Phase 1

Completed

Interventions: Drug: temsirolimus
Biological: bevacizumab
Genetic: polymorphism analysis
Other: laboratory biomarker analysis

Brief Summary: RATIONALE: Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving temsirolimus together with bevacizumab may be a better way to block tumor growth.

PURPOSE: This phase I/II trial is studying the side effects and best dose of temsirolimus when given together with bevacizumab and to see how well it works in treating patients with hormone-resistant metastatic prostate cancer that did not respond to chemotherapy.

Detailed Description: PRIMARY OBJECTIVES:

I. The primary objective of the Phase I portion of this study is to determine the maximum tolerated dose (MTD) of temsirolimus in combination with AVASTIN in subjects with chemotherapy refractory metastatic CRPC.

II. The primary objective for the Phase II portion of this study is to evaluate the objective response frequency (PSA and RECIST-Response Evaluation Criteria in Solid Tumors-defined) of the combination of temsirolimus and AVASTIN in patients with chemotherapy refractory metastatic CRPC.

SECONDARY OBJECTIVES:

I. To evaluate the effect of the combination of temsirolimus and AVASTIN on time to clinical progression and overall survival in patients with chemotherapy refractory metastatic CRPC.

II. To further evaluate the safety of temsirolimus given in combination with AVASTIN in chemotherapy refractory metastatic CRPC patients at the dose established in our phase I safety phase.

III. To determine the presence of circulating tumor cells (CTCs) and status of single nucleotide polymorphism (SNPs) in CRPC patients. (Exploratory)

OUTLINE: Patients receive temsirolimus IV over 30-60 minutes once weekly and bevacizumab IV over 30-90 minutes once every two weeks . Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 28 days.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Arm 1: Combination of temsirolimus and AVASTIN	bevacizumab	Patients receive temsirolimus IV over 30-60 minutes once weekly and bevacizumab IV over 30-90 minutes once every two weeks . Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm 1: Combination of temsirolimus and AVASTIN	polymorphism analysis	Patients receive temsirolimus IV over 30-60 minutes once weekly and bevacizumab IV over 30-90 minutes once every two weeks . Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm 1: Combination of temsirolimus and AVASTIN	laboratory biomarker analysis	Patients receive temsirolimus IV over 30-60 minutes once weekly and bevacizumab IV over 30-90 minutes once every two weeks . Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
Arm 1: Combination of temsirolimus and AVASTIN	temsirolimus	Patients receive temsirolimus IV over 30-60 minutes once weekly and bevacizumab IV over 30-90 minutes once every two weeks . Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD) of Temsirolimus (Phase I)	at 24 weeks	Participants received temsirolimus (20mg or 25mg IV weekly) in combination with a fixed dose of IV bevacizumab (10mg/kg every 2 weeks). The MTD was determined to be the dose at which no unacceptable toxicities were observed.
Objective Response (Dose Level 2)	change from baseline to 12 weeks	PSA (Prostate-Specific Antigen) test will be performed every 4 weeks prior to receiving treatment. PSA response will be measured as the number of participants that had a decline observed from baseline.

Secondary Outcome Measures

Name	Time	Method
Time to Clinical Progression	12 weeks	To evaluate the effect of the combination of temsirolimus and AVASTIN on time (in months) to clinical progression from start of treatment. Progressive Disease according to RECIST Criteria is defined as : At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Overall Survival	baseline to end of study, up to 3.5 years	Time in months from on study to time of death
Number of Patients With Toxicity as Assessed by CTCAE v3.0 (Common Toxicity Criteria for Adverse Effects)	at 24 weeks	To further evaluate the safety of temsirolimus given in combination with AVASTIN in chemotherapy refractory metastatic CRPC patients at the dose established in our phase I safety phase. Specific toxicities are listed in the SAE and AE results.

Locations (3): Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
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Cleveland, Ohio, United States
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
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Cleveland, Ohio, United States
CCF-Willoughby Hills
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Willoughby Hills, Ohio, United States