Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Rapid Hormone Cycling With Testosterone and Leuprolide Combined With Docetaxel in Treating Patients With Recurrent or Metastatic Adenocarcinoma (Cancer) of the Prostate

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	MSKCC-03076 NCT00070369

Objectives

Primary

1. 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

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

Entry Criteria

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]

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

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 3 months

Hematopoietic

• WBC at least 3,500/mm³
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

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

Outcomes

PSA ≤ 0.05 ng/mL after radical prostatectomy
PSA ≤ 0.5 ng/mL after radiation therapy or no prior therapy
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
Antitumor effects in terms of changes in prostate-specific antigen
Affects of testosterone administration on CYP3A activity as measured by the erythromycin breast test and docetaxel pharmacokinetics

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.

Rathkopf D, Carducci MA, Morris MJ, et al.: Phase II trial of docetaxel with rapid androgen cycling for progressive noncastrate prostate cancer. J Clin Oncol 26 (18): 2959-65, 2008.[PUBMED Abstract]

Nordquist LT, Morris MJ, Sauter N, et al.: Rapid hormone cycling for prostate cancer (PC) patients: the MENS cycle . [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-1669, 415, 2003.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Dana Rathkopf, MD, Principal investigator		Ph: 646-422-4379; 800-525-2225 Email: rathkopd@mskcc.org

Registry Information
Official Title		Docetaxel With Rapid Hormonal Cycling As A Treatment For Patients With Prostate Cancer
Trial Start Date		2003-07-08
Registered in ClinicalTrials.gov		NCT00070369
Date Submitted to PDQ		2003-08-28
Information Last Verified		2006-04-01
NCI Grant/Contract Number		CA08748

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