Official Title: “Docetaxel With Rapid Hormonal Cycling As A Treatment For Patients With Prostate Cancer”

RATIONALE: Testosterone can stimulate the growth of prostate cancer cells. Hormone therapy using leuprolide may fight prostate cancer by reducing the production of testosterone. Some tumors become resistant to hormone therapy. Alternating short schedules of testosterone and leuprolide combined with a chemotherapy drug, such as docetaxel, may reduce resistance to the hormone therapy and kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving testosterone and leuprolide together with docetaxel works in treating patients with recurrent or metastatic adenocarcinoma of the prostate (prostate cancer).

Study Type: Interventional

Study Design: Treatment, Open Label

OBJECTIVES:

Primary - Determine the efficacy of rapid hormonal cycling with testosterone and leuprolide in combination with docetaxel, in terms of obtaining a durable decline in prostate-specific antigen level or reduction of abnormal sites of disease, in patients with recurrent or non-castrate metastatic adenocarcinoma of the prostate.

Secondary - Determine the safety of this regimen in these patients. - Determine the antitumor effects and changes in measurable disease in patients treated with this regimen. - Determine the affects of testosterone administration on CYP3A activity and docetaxel pharmacokinetics in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical state (rising prostate-specific antigen vs non-castrate metastatic disease).

Patients receive leuprolide intramuscularly and docetaxel IV over 1 hour on day 1 and testosterone gel topically on days 22-28. Treatment repeats every 28 days for 6 courses* in the absence of disease progression or unacceptable toxicity.

NOTE: *Testosterone gel is applied only during courses 1-5.

Patients are followed monthly for 1 year and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 76 patients (38 per stratum) will be accrued for this study within approximately 2 years.

Intervention(s) in this Clinical Trial

• Drug: docetaxel
• Drug: leuprolide acetate
• Drug: therapeutic testosterone

Primary Measures

• PSA ≤ 0.05 ng/mL after radical prostatectomy
  • Safety Issue?: No
• PSA ≤ 0.5 ng/mL after radiation therapy or no prior therapy
  • Safety Issue?: No
• PSA ≤ 2 ng/mL for patients with clinical metastases without prior definitive therapy with a serum testosterone level that has returned to pretreatment baseline, 18 months after the start of therapy
  • Safety Issue?: No

Secondary Measures

• Safety
  • Safety Issue?: Yes
• Antitumor effects in terms of changes in prostate-specific antigen
  • Safety Issue?: No
• Affects of testosterone administration on CYP3A activity as measured by the erythromycin breast test and docetaxel pharmacokinetics
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate in either of the following clinical states:
• History of localized disease with prior definitive radiotherapy or surgery
• Biochemically progressive disease*
• No radiographically evident disease
• Radiographically evident non-castrate metastatic disease at the time of diagnosis or after treatment for localized disease
• Radiographically (new osseous lesions or more than a 25% increase in a bidimensionally measurable tumor mass) AND/OR biochemically progressive disease*
• Testosterone greater than 180 mg/dL
• No active CNS or epidural tumor NOTE: *Biochemically progressive disease, defined as an increase of at least 50% in the prostate-specific antigen (PSA) level across at least 3 determinations each measured more than 2 weeks apart with a baseline PSA of at least 2 ng/mL

PATIENT CHARACTERISTICS:

• Age
• 18 and over
• Performance status
• Karnofsky 70-100%
• Life expectancy
• At least 3 months
• Hematopoietic
• WBC at least 3,500/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin greater than 8.0 g/dL
• Hepatic
• Bilirubin normal
• SGOT and SGPT less than 2.5 times upper limit of normal (ULN) AND alkaline phosphatase less than ULN OR
• Alkaline phosphatase no greater than 4 times ULN AND SGPT and SGOT less than ULN
• Renal
• Creatinine no greater than 1.6 mg/dL OR
• Creatinine clearance at least 60 mL/min
• Cardiovascular
• No New York Heart Association class III or IV cardiac disease
• Pulmonary
• No severe debilitating pulmonary disease
• Other
• Fertile patients must use effective contraception during and for at least 6 months after study treatment
• No uncontrolled serious active infection
• No grade 2 or greater peripheral neuropathy
• No prior severe hypersensitivity reaction to drugs formulated with polysorbate 80

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• No concurrent immunotherapy
• Chemotherapy
• No prior chemotherapy
• No other concurrent chemotherapy
• Endocrine therapy
• Prior hormonal therapy before radiotherapy or radical prostatectomy allowed provided the total duration of therapy is no more than 6 months
• No more than 1 course of intermittent hormonal therapy up to a maximum exposure of 6 months
• Radiotherapy
• See Disease Characteristics
• No concurrent therapeutic radiotherapy
• Surgery
• See Disease Characteristics
• Other
• At least 7 days since prior inhibitors or inducers of CYP3A, including the following:
• Fluconazole
• Itraconazole
• Macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin, and troleanodomycin)
• Midazolam
• Nifedipine
• Uncaria tomentosa (cat's claw)
• Chamomile (matricaria chamomila)
• Echinacea
• Hydrastis canadensis (Goldenseal)
• Glycyrrhiza glabra (licorice)
• Milk thistle
• Trifolium pratense (wild cherry)
• Garlic
• No concurrent inhibitors or inducers of CYP3A during courses 1 and 2
• No concurrent administration of the following drugs:
• Phenytoin
• Carbamazepine
• Barbiturates
• Rifampin
• Phenobarbital
• Hypericum perforatum (St. John's wort)
• Ketoconazole
• No other concurrent experimental anticancer medication

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Memorial Sloan-Kettering Cancer Center

Overall Clinical Trial Officials and Contacts

Dana Rathkopf, MD Principal Investigator Memorial Sloan-Kettering Cancer Center  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00070369

Study ID Number: CDR0000331936

ClinicalTrials.gov Identifier: NCT00070369

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database