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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 1

Conditions: Prostate Cancer

Treatments: Drug: therapeutic testosterone

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00006044

P01CA005826 (U.S. NIH Grant/Contract)

P30CA008748 (U.S. NIH Grant/Contract)

MSKCC-99115

99-115

NCI-G00-1818

Details and patient eligibility

About

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.

Full 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.

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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