Testosterone in Treating Patients With Progressive Prostate Cancer That No Longer Responds to Hormone Therapy

NCT ID: NCT00006044

Last Updated: 2013-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-02-29

Brief Summary

RATIONALE: High doses of testosterone may be effective in killing prostate cancer cells that no longer respond to hormone therapy.

PURPOSE: Phase I trial to study the effectiveness of testosterone in treating patients who have progressive prostate cancer that no longer responds to hormone therapy.

Detailed Description

OBJECTIVES:

• Determine the safety and maximum tolerated dose of exogenously administered testosterone in patients with progressive androgen-independent prostate cancer who have been in castrate state either surgically or pharmacologically for a minimum of 1 year.
• Assess the changes in expression of androgen receptor and other receptors in human biopsy specimens or circulating tumor cells before and after this treatment in this patient population.

OUTLINE: This is a dose-escalation study.

Patients receive testosterone via an enhanced absorption transdermal system continuously for 28 days. The transdermal patches are changed daily.

Cohorts of 3-6 patients receive a fixed daily dose of testosterone with escalating duration of exposure until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicities.

Patients are followed at day 1 and at weeks 2 and 4.

PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study.

Conditions

Prostate Cancer

Study Design

• Primary Study Purpose: TREATMENT

Interventions

therapeutic testosterone

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed androgen independent metastatic prostate cancer
• Progressive disease manifested by either:

• New osseous lesions by bone scan or a greater than 25% increase in bidimensionally measurable soft tissue disease or the appearance of new sites of disease by MRI or CT scan OR
• Minimum of 3 rising PSA values from baseline that are obtained 1 week or more apart, or 2 rising PSA values more than 1 month apart, where the percentage increase over the range of values is at least 25%
• Castrate state by orchiectomy or gonadotropin-releasing hormone analogues for minimum of 1 year

• Testosterone no greater than 30 ng/mL
• Measurable disease
• Metastatic disease by bone scan, MRI, or CT scan
• Rising PSA values
• If receiving antiandrogen therapy, must have shown progressive disease off treatment
• No active CNS or epidural tumor

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 2.0 mg/dL
• SGOT less than 3 times upper limit of normal
• PTT less than 14 seconds

Renal:

• Creatinine less than 2.0 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No New York Heart Association class III or IV cardiac disease

Pulmonary:

• No severe debilitating pulmonary disease

Other:

• No infection requiring IV antibiotics
• No other severe medical problems that would increase risk for toxicity

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Recovered from prior biologic therapy
• No concurrent immunotherapy

Chemotherapy:

• Recovered from prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy:

• See Disease Characteristics
• If no prior orchiectomy, must continue on gonadotropin-releasing hormone analogs to maintain castrate levels of testosterone
• No concurrent finasteride
• No other concurrent hormonal therapy

Radiotherapy:

• Recovered from prior radiotherapy
• No concurrent radiotherapy to an indicator lesion

Surgery:

• See Disease Characteristics
• Recovered from prior surgery
• No concurrent surgery on only measurable lesion

Other:

• At least 4 weeks since other prior investigational anticancer drugs and recovered
• No other concurrent investigational anticancer agents

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Principal Investigators

Michael Morris, MD

Role: STUDY_CHAIR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

References

Morris MJ, Huang D, Kelly WK, Slovin SF, Stephenson RD, Eicher C, Delacruz A, Curley T, Schwartz LH, Scher HI. Phase 1 trial of high-dose exogenous testosterone in patients with castration-resistant metastatic prostate cancer. Eur Urol. 2009 Aug;56(2):237-44. doi: 10.1016/j.eururo.2009.03.073. Epub 2009 Apr 3.

Reference Type: RESULT

PMID: 19375217 (View on PubMed)

Other Identifiers

P30CA008748

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P01CA005826

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MSKCC-99115

Identifier Type: -

Identifier Source: secondary_id

NCI-G00-1818

Identifier Type: -

Identifier Source: secondary_id

99-115

Identifier Type: -

Identifier Source: org_study_id