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Temsirolimus and Vorinostat in Treating Patients With Metastatic Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01174199
Recruitment Status : Terminated (no value in finding efficacy)
First Posted : August 3, 2010
Last Update Posted : September 13, 2016
Merck Sharp & Dohme Corp.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Adenocarcinoma of the Prostate Hormone-resistant Prostate Cancer Recurrent Prostate Cancer Stage IV Prostate Cancer Drug: vorinostat Drug: temsirolimus Other: laboratory biomarker analysis Procedure: positron emission tomography/computed tomography Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of the mTOR Inhibitor Temsirolimus in Combination With the HDAC Inhibitor Vorinostat in Patients With Metastatic Prostate Cancer
Study Start Date : February 2012
Actual Primary Completion Date : August 2015
Actual Study Completion Date : August 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Arm I
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.
Drug: vorinostat
Given orally
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza

Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • rapamycin analog CCI-779
  • Torisel

Other: laboratory biomarker analysis
Correlative study

Procedure: positron emission tomography/computed tomography
PET scan

Primary Outcome Measures :
  1. Frequencies of DLT and toxicity [ Time Frame: 4 yrs ]
  2. Adverse events [ Time Frame: 4 years ]

Secondary Outcome Measures :
  1. Median survival, median progression-free survival, and frequency of deaths [ Time Frame: 4 years ]
  2. PSA response [ Time Frame: Every 2 cycles of treatment ]
  3. Changes in expression of bone remodeling markers and angiogenesis-related gene and protein expression [ Time Frame: Prior to each cycle ]
  4. Changes in tumor metabolism as assessed by PET/CT scan [ Time Frame: Prior to each cycle ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No


  • Patients must have a histologically confirmed diagnosis of adenocarcinoma of the prostate that is hormone refractory and with evidence of progressive metastatic disease following docetaxel treatment by any of the following:

    • Increased serum prostate-specific antigen (PSA) levels confirmed by 3 consecutive PSA measurements (at least 2 weeks apart), the first sample to be taken at least 6 weeks after bicalutamide or megestrol acetate withdrawal AND/OR
    • Progression of bidimensionally measurable soft tissue (nodal) metastasis by CT scan or MRI within the past 4 weeks AND/OR
    • Progression of bone disease by at least two new bone lesions on bone scan confirmed by a second bone scan
  • Patients should be without persisting >= grade 2 hematological/non-hematological toxicities from previous treatments that would preclude evaluation of toxic effects of study treatment.Grade 1 residual toxicity will be acceptable. Patients should be off prior therapies at least 4 weeks before starting study treatment
  • Prior palliative radiation to metastatic lesion(s) is permitted, provided there is at least one measurable and/or evaluable lesion(s) that has not been radiated
  • Castrate levels of serum testosterone (=< 50 ng/dL or 1.0 mmol/L) confirmed within two weeks prior to Day 1 of treatment. Testosterone levels will not be required for patients who have had bilateral orchiectomy
  • ECOG performance status 0-1
  • Life expectancy of greater than 6 months
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelets >= 100,000/mm^3
  • Hgb >= 9g/L
  • Total bilirubin =< 1.5 x laboratory upper limit of normal (ULN)
  • AST(SGOT)/ALT(SGPT) <= 2.5 x laboratory ULN
  • Creatinine =< 1.5 x laboratory ULN or calculated creatinine clearance >= 50 ml/min
  • Serum amylase =< ULN (If > ULN, confirm pancreatic amylase < 1.1 ukat/L and serum lipase < ULN)
  • PT/INR <= 1.5
  • Urine protein < 1+ or if >= 1 then 24-hour urine protein should be obtained and should be < 1000 mg
  • Serum cholesterol < ULN with or without treatment for hyperlipidemia; if > ULN and untreated, may be rescreened for eligibility after treatment
  • Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of temsirolimus will be determined following review of their case by the Principal Investigator
  • Patients, if sexually active, will agree to use adequate contraceptive methods (barrier contraceptive with spermicide, vasectomy, abstinence) prior to study entry and for the duration of study participation
  • Ability to understand and the willingness to sign a written informed consent document
  • No evidence (>= 5 years) of prior malignancies except successfully treated basal cell or squamous cell carcinoma of the skin


  • Prior use of HDAC or mTOR inhibitors
  • Patients with known brain metastases
  • Any medical condition, including the presence of laboratory abnormalities, which confounds the ability to interpret data from the study or places the patient at unacceptable risk if he participates in the study
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or temsirolimus
  • Concurrent use of other anticancer agents or treatments except LHRH antagonists
  • Uncontrolled intercurrent illness including, but not limited to the following:(a)Ongoing or active infection including viral hepatitis,(b)Symptomatic congestive heart failure (New York Association Class II, III, or IV),(c) unstable angina pectoris requiring nitrate therapy,(d) prior myocardial infarction,(e)severe uncontrolled ventricular cardiac arrhythmias,(f) uncontrolled hypertension (defined as blood pressure of > 160 mmHg systolic and/or > 90 mmHg diastolic on medication),(g)electrocardiographic evidence of acute ischemia(h)Psychiatric illness/social situations that would limit compliance with study requirements
  • Known positive serology for HIV and known history of HIV because of the potential for pharmacokinetic unforeseen toxicity and morbidity in an immunocompromised patient
  • Any treatment modalities, including radiation and surgery, not discontinued at least 4 weeks prior to treatment in this study
  • Chronic Hepatitis with advanced, decompensated hepatic disease or cirrhosis of the liver or history of chronic virus hepatitis or known viral hepatitis carrier (patient recovered from Hepatitis A will be allowed to enter the study)
  • Simultaneous participation in any other study involving investigational drugs or having participated in a study less than 4 weeks prior to treatment in this study
  • No investigational or commercial agents or therapies other than those described in the study may be administered with the intent to treat the patient's malignancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01174199

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United States, Maryland
The Sydney Kimmel Comprehensive Center at John Hopkins
Baltimore, Maryland, United States, 21287
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Sponsors and Collaborators
Roswell Park Cancer Institute
Merck Sharp & Dohme Corp.
National Cancer Institute (NCI)
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Principal Investigator: Saby George, MD Roswell Park Cancer Institute

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Responsible Party: Roswell Park Cancer Institute Identifier: NCT01174199     History of Changes
Other Study ID Numbers: RPCI I 150709
First Posted: August 3, 2010    Key Record Dates
Last Update Posted: September 13, 2016
Last Verified: September 2016
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents