Hormone Therapy and Temsirolimus in Treating Patients With Relapsed Prostate Cancer

Adenocarcinoma of the Prostate Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00512668
• Other study ID #: NCI-2012-03098
• Secondary ID: 2007-0025
• Status: Terminated
• Phase: Phase 1
• First received: August 6, 2007
• Last updated: January 4, 2013
• Start date: September 2007

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Prostate
• Prostatic Neoplasms
• Recurrent Prostate Cancer

Intervention

Drug:
• leuprolide acetate
Given intramuscularly
• goserelin acetate
Given subcutaneously
• bicalutamide
Given PO
• nilutamide
Given PO
• flutamide
Given PO
• temsirolimus
Given IV

Other:
• laboratory biomarker analysis
Optional correlative studies

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

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