Temsirolimus and Vorinostat in Treating Patients With Metastatic Prostate Cancer

NCT01174199 | Terminated Phase 1 DMC

• 2 other identifiers: RPCI I 150709NCI-2009-01537
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

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.

Conditions

Prostate Cancer; Adenocarcinoma of the Prostate; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage IV Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Frequencies of DLT and toxicity

  4 yrs

• Adverse events

  4 years

Secondary Outcomes (4)

• Median survival, median progression-free survival, and frequency of deaths

  4 years

• 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

• Changes in tumor metabolism as assessed by PET/CT scan

  Prior to each cycle

Study Arms (1)

Arm I

EXPERIMENTAL

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; Drug: temsirolimus; Other: laboratory biomarker analysis; Procedure: positron emission tomography/computed tomography

Interventions

vorinostat DRUG

Given orally

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

Arm I

temsirolimus DRUG

Given IV

Also known as: CCI-779, cell cycle inhibitor 779, rapamycin analog CCI-779, Torisel

Arm I

laboratory biomarker analysis OTHER

Correlative study

Arm I

positron emission tomography/computed tomography PROCEDURE

PET scan

Arm I

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

The Sydney Kimmel Comprehensive Center at John Hopkins

Baltimore, Maryland, 21287, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Vorinostat; temsirolimus; Sirolimus; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Macrolides; Lactones; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Saby George, MD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2010
• First Posted: August 3, 2010
• Study Start: February 1, 2012
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2016
• Last Updated: October 3, 2022

Record last verified: 2022-09

Locations

US (2)