Hormone Therapy and Temsirolimus in Treating Patients With Relapsed Prostate Cancer

January 4, 2013 updated by: National Cancer Institute (NCI)

Phase Ib Study of Limited Androgen Ablation and Two Dose Levels of Temsirolimus (NSC#683864) in Patients With Prostate Cancer Who Have a Biochemical Relapse After Prostatectomy and/or Radiotherapy

This phase I trial is studying the side effects and best dose of temsirolimus when given together with hormone therapy in treating patients with relapsed prostate cancer. Androgens can cause the growth of prostate cancer cells. Hormone therapy may fight prostate cancer by lowering the amount of androgens the body makes. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving hormone therapy together with temsirolimus may kill more tumor cells

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To characterize safety and drug-related adverse events of two doses (15 and 25 mg) of intravenous weekly temsirolimus combined with short term complete androgen ablation and to select a favorable and tolerable dose for prostate cancer patients who experience biochemical failure after prostatectomy and/or radiation therapy.

SECONDARY OBJECTIVES:

I. To archive tissue and blood components for future study of molecular markers of response and disease progression.

II. To evaluate the effects of 2 dose levels of temsirolimus on changes in the phosphorylation state of proteins in the mTOR pathway using western blots on peripheral blood mononuclear cells (PBMCs).

OUTLINE:

Patients receive combined androgen ablation therapy comprising a luteinizing hormone-releasing hormone analogue (i.e., leuprolide acetate intramuscularly once monthly or goserelin subcutaneously every 3 months) and an oral anti-androgen drug (i.e., bicalutamide or nilutamide once daily or flutamide 3 times daily) on days 1-90.* Beginning on day 60 of hormonal therapy, patients receive temsirolimus IV over 30 minutes once weekly. Treatment with temsirolimus continues for up to 36 weeks in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients may receive no more than 3 months of hormonal therapy, including therapy initiated within 2 months of study entry.

After completion of study therapy, patients are followed at 30 days.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • All patients must sign an informed consent indicating that they are aware of the investigational nature of this study; patients must also have signed an authorization for the release of their protected health information
  • Patients must have histologically confirmed adenocarcinoma of the prostate recurring after local therapy (radical prostatectomy and/or radiation therapy) as evidenced by rising serum PSA
  • Prostate-Specific Antigen (PSA) Doubling Time (PSADT) =< 12 months after local therapy (prostatectomy and/or definitive radiation) as determined by linear regression of all available PSA values within 6 months of initiation of androgen ablation (for patients who underwent prostatectomy, at least one PSA measurement of >= 1.0 ng/mL; for patients who underwent radiation, at least one PSA measurement of >= 3.0 ng/mL and >= 150% postradiation nadir)
  • No evidence of metastasis as determined by bone scan or computed tomography (CT) scan
  • Initiation of Androgen Ablation of less than 8 weeks' duration prior to study entry is permitted
  • Leukocytes ≥ 3,000/mcl
  • Absolute neutrophil count ≥ 1,000/mcl

  • Hemoglobin ≥ 8.0g/dl

    • Eligibility level for hemoglobin may be reached by transfusion
  • Platelet count >= 100,000/μL
  • Total bilirubin ≤1.5 X laboratory ULN
  • AST and/or ALT ≤ 3 X laboratory ULN
  • Creatinine ≤ 1.5 X laboratory ULN OR calculated creatinine clearance ≥ 60 ml/min/1.73 m^2 for patients w/creatinine levels above the laboratory ULN
  • Serum cholesterol level < 350 mg/dl
  • Triglyceride level < 300mg/dl
  • ECOG performance status 0, 1 or 2
  • The effects of Temsirolimus on the developing human fetus are unknown; for this reason men must agree to use contraception from the time of study enrollment continuing for the duration of study participation
  • Patients must be registered in the MDACC institutional database prior to treatment with study drug
  • PSA < 40 ng/ml

Exclusion Criteria:

  • Patients with histologic variants other than adenocarcinoma in the primary tumor
  • Patients may not be receiving any other investigational agents
  • Patients may not be receiving concomitant immunotherapy or immunosuppressive therapy
  • Patients may not have received prior systemic treatment for prostate cancer (other than no more than 3 months of prior treatment with androgen ablation in neoadjuvant and/or adjuvant setting and at least a year must have elapsed since last administration) unless initiation of Androgen Ablation of less than 8 weeks' duration prior to study entry is permitted
  • Patient with uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring parenteral therapy on day 1 of protocol treatment, symptomatic congestive heart failure resulting in a resting O2 saturation of < 92% on room air, unstable angina pectoris, myocardial infarction within the previous 6 months, or use of ongoing maintenance therapy for life-threatening ventricular arrhythmia, known pulmonary hypertension or pneumonitis
  • Patients in a severely compromised immunological state, including being positive for the human immunodeficiency virus (HIV) due to possible pharmacokinetic interactions with HAART therapy
  • Patients diagnosed with acute or chronic hepatitis B or C
  • Patients using immunosuppressive agents, including intravenous corticosteroids, within 3 weeks of study entry
  • Patients must not have a history of any other cancer (except nonmelanoma skin cancer), unless in complete remission and off of all therapy for that disease for a minimum of 3 years

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (hormone therapy, temsirolimus)

Patients receive combined androgen ablation therapy comprising a luteinizing hormone-releasing hormone analogue (i.e., leuprolide acetate intramuscularly once monthly or goserelin subcutaneously every 3 months) and an oral anti-androgen drug (i.e., bicalutamide or nilutamide once daily or flutamide 3 times daily) on days 1-90.* Beginning on day 60 of hormonal therapy, patients receive temsirolimus IV over 30 minutes once weekly. Treatment with temsirolimus continues for up to 36 weeks in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients may receive no more than 3 months of hormonal therapy, including therapy initiated within 2 months of study entry.
Drug: temsirolimus
Given IV
Other Names:
  • Torisel
  • CCI-779
  • cell cycle inhibitor 779
Other: laboratory biomarker analysis
Optional correlative studies
Drug: bicalutamide
Given PO
Other Names:
  • Casodex
  • CDX
Drug: leuprolide acetate
Given intramuscularly
Other Names:
  • Enantone
  • LEUP
  • Lupron
  • Lupron Depot
Drug: goserelin acetate
Given subcutaneously
Other Names:
  • ICI-118630
  • ZDX
  • Zoladex
Drug: nilutamide
Given PO
Other Names:
  • Anandron
  • Nilandron
  • ANAN
Drug: flutamide
Given PO
Other Names:
  • Eulexine
  • FLUT
  • Sch 13521
  • Eulexin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety, in terms of drug-related adverse events of two doses of temsirolimus following androgen ablation
Time Frame: 180 days
180 days
Favorable and tolerable dose for prostate cancer patients who experience biochemical failure after prostatectomy and/or radiation therapy
Time Frame: 180 days
180 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Christopher Logothetis, M.D. Anderson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2007

Primary Completion (Actual)

January 1, 2008

Study Registration Dates

First Submitted

August 6, 2007

First Submitted That Met QC Criteria

August 6, 2007

First Posted (Estimate)

August 8, 2007

Study Record Updates

Last Update Posted (Estimate)

January 7, 2013

Last Update Submitted That Met QC Criteria

January 4, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-03098
  • 2007-0025

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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