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Rapid Hormone Cycling With Testosterone and Leuprolide Combined With Docetaxel in Treating Patients With Recurrent or Metastatic Adenocarcinoma (Cancer) of the Prostate
This study is ongoing, but not recruiting participants.
First Received: October 3, 2003   Last Updated: July 26, 2008   History of Changes
Sponsors and Collaborators: Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00070369
  Purpose

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).


Condition Intervention Phase
Prostate Cancer
Drug: docetaxel
Drug: leuprolide acetate
Drug: therapeutic testosterone
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Docetaxel With Rapid Hormonal Cycling As A Treatment For Patients With Prostate Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • PSA ≤ 0.05 ng/mL after radical prostatectomy [ Designated as safety issue: No ]
  • PSA ≤ 0.5 ng/mL after radiation therapy or no prior therapy [ Designated as 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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety [ Designated as safety issue: Yes ]
  • Antitumor effects in terms of changes in prostate-specific antigen [ Designated as safety issue: No ]
  • Affects of testosterone administration on CYP3A activity as measured by the erythromycin breast test and docetaxel pharmacokinetics [ Designated as safety issue: No ]

Study Start Date: July 2003
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00070369

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Dana Rathkopf, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
Publications:
Rathkopf D, Carducci MA, Morris MJ, Slovin SF, Eisenberger MA, Pili R, Denmeade SR, Kelsen M, Curley T, Halter M, Collins C, Fleisher M, Heller G, Baker SD, Scher HI. Phase II trial of docetaxel with rapid androgen cycling for progressive noncastrate prostate cancer. J Clin Oncol. 2008 Jun 20;26(18):2959-65.
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.

Study ID Numbers: CDR0000331936, MSKCC-03076
Study First Received: October 3, 2003
Last Updated: July 26, 2008
ClinicalTrials.gov Identifier: NCT00070369     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adenocarcinoma of the prostate
recurrent prostate cancer
stage IV prostate cancer

Study placed in the following topic categories:
Antineoplastic Agents, Hormonal
Genital Neoplasms, Male
Prostatic Diseases
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Urogenital Neoplasms
Methyltestosterone
Genital Diseases, Male
Hormones
Recurrence
Testosterone 17 beta-cypionate
Carcinoma
Docetaxel
Anabolic Agents
Testosterone
Leuprolide
Adenocarcinoma
Prostatic Neoplasms
Androgens
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Prostatic Diseases
Genital Neoplasms, Male
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Urogenital Neoplasms
Reproductive Control Agents
Hormones
Docetaxel
Neoplasms by Site
Leuprolide
Therapeutic Uses
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Methyltestosterone
Genital Diseases, Male
Pharmacologic Actions
Testosterone 17 beta-cypionate
Carcinoma
Testosterone
Neoplasms
Anabolic Agents
Fertility Agents, Female
Fertility Agents
Adenocarcinoma
Prostatic Neoplasms
Neoplasms, Glandular and Epithelial
Androgens

ClinicalTrials.gov processed this record on September 03, 2009