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

Condition(s) targeted: Prostate Cancer

Intervention: docetaxel (Drug); leuprolide acetate (Drug); therapeutic testosterone (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Memorial Sloan-Kettering Cancer Center

Official(s) and/or principal investigator(s):
Dana Rathkopf, MD, Principal Investigator, Affiliation: Memorial Sloan-Kettering Cancer Center

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).

Official title: Docetaxel With Rapid Hormonal Cycling As A Treatment For Patients With Prostate Cancer

Study design: Treatment, Open Label

Primary outcome:

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

Secondary outcome:

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

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

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

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

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231-2410, United States

Memorial Sloan-Kettering Cancer Center, New York, New York 10021, United States

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

Related publications:

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.

Starting date: July 2003
Last updated: May 23, 2008