Chemotherapy With or Without Biological Therapy in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00005847
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : January 27, 2010
National Cancer Institute (NCI)
Information provided by:
Eastern Cooperative Oncology Group

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. It is not yet known which treatment regimen is more effective in treating metastatic prostate cancer.

PURPOSE: Randomized phase II trial to compare the effectiveness of combination chemotherapy with that of chemotherapy plus biological therapy in treating patients who have progressive or metastatic prostate cancer that has not responded to hormone therapy.

Condition or disease Intervention/treatment Phase
Prostate Cancer Biological: recombinant interferon alfa Drug: estramustine phosphate sodium Drug: isotretinoin Drug: mitoxantrone hydrochloride Drug: paclitaxel Drug: vinorelbine ditartrate Phase 2

Detailed Description:


  • Compare the effect of estramustine, mitoxantrone, and vinorelbine vs isotretinoin, interferon alfa, and paclitaxel on PSA response in patients with metastatic hormone-refractory prostate cancer.
  • Determine the toxic effects of each regimen in this patient population.
  • Determine the effect of each regimen on pain, fatigue, and quality of life in these patients.
  • Determine the objective response rate among the subset of patients who have bidimensionally measurable disease to each regimen after treatment.
  • Determine the effect of each regimen on peripheral blood mononuclear cell BCL-2 in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease (measurable vs nonmeasurable and elevated PSA). Patients are randomized to one of two treatment arms.

  • Arm I: Patients receive vinorelbine IV over 10 minutes on days 2 and 9 followed by mitoxantrone IV over 10 minutes on day 2 only. Oral estramustine is administered every 12 hours on days 1-5. Courses repeat every 3 weeks in the absence of unacceptable toxicity, disease progression, or administration of the maximum cumulative dose of mitoxantrone.
  • Arm II: Patients receive oral isotretinoin and interferon alfa subcutaneously on days 1 and 2 and paclitaxel IV over 1 hour on day 2 weekly for 6 weeks. Courses repeat every 8 weeks in the absence of unacceptable toxicity or disease progression.

Quality of life is assessed at baseline, on day 2 of courses 2, 4, and 6 (arm I), on day 22 of course 1 and day 1 of courses 2 and 3 (arm II), and then at completion of treatment.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 70-114 patients (35-57 per arm) will be accrued for this study within 14-23 months.

Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Mitoxantrone, Estramustine and Navelbine or 13-cis Retinoic Acid, Interferon and Paclitaxel in Patients With Metatstatic Hormone Refractory Prostate Cancer
Study Start Date : January 2001
Actual Primary Completion Date : July 2004

Resource links provided by the National Library of Medicine

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No


  • Histologically confirmed adenocarcinoma of the prostate
  • Evidence of progressive metastatic disease (e.g., bone, pelvic mass, lymph node, liver or lung metastases)

    • Radiologic evidence of hydronephrosis only does not constitute evidence of metastatic disease
  • Must not have an elevated serum alkaline phosphatase or PSA level as only evidence of disease
  • If bone metastases only (i.e., lacking soft tissue disease), must have PSA level of at least 20 ng/mL
  • If soft tissue metastases and/or visceral disease, must have either bidimensionally measurable disease or PSA level of at least 20 ng/mL
  • Must have had prior bilateral orchiectomy or other primary hormonal therapy (e.g., estrogen therapy or LHRH blocker plus flutamide) with evidence of treatment failure
  • No carcinomatous meningitis or brain metastases



  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • Not specified


  • WBC at least 4,000/mm^3
  • Granulocyte count at least 2,000/mm^3
  • Platelet count at least 100,000/mm^3


  • See Disease Characteristics
  • Bilirubin no greater than 1.5 mg/dL
  • SGOT/SGPT no greater than 2 times upper limit of normal


  • Creatinine no greater than 2.0 mg/dL OR
  • Creatinine clearance at least 50 mL/min


  • No active angina pectoris
  • No New York Heart Association class III or IV heart disease
  • No myocardial infarction within the past 6 months
  • No deep venous thrombosis
  • LVEF at least 50% by MUGA


  • Fertile patients must use effective contraception during and for 1 month after study
  • Prior malignancy allowed provided curatively treated and disease free for appropriate time period for specific cancer
  • No other serious medical illness or active infection that would preclude protocol therapy
  • No concurrent prolonged exposure to sunlight
  • No concurrent alcohol consumption


Biologic therapy:

  • Not specified


  • No prior chemotherapy, including neoadjuvant chemotherapy or single-agent estramustine

Endocrine therapy:

  • See Disease Characteristics
  • If no prior bilateral orchiectomy, must continue LHRH agonist therapy (e.g., depot leuprolide or goserelin)
  • At least 4 weeks since prior flutamide or flutamide with evidence of progressive disease
  • At least 6 weeks since prior bicalutamide with evidence of progressive disease


  • More than 4 weeks since prior radiotherapy
  • No prior strontium chloride Sr 89, samarium Sm 153 lexidronam pentasodium, or other radioisotope therapies


  • See Disease Characteristics


  • Recovered from all toxic effects due to prior treatment for prostate cancer
  • No concurrent milk, milk products, antacids, calcium-containing drugs, or any food with estramustine (arm I only)
  • No concurrent vitamin supplements containing vitamin A (arm II only)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00005847

United States, Colorado
CCOP - Colorado Cancer Research Program, Incorporated
Denver, Colorado, United States, 80224
United States, Georgia
Emory University Hospital - Atlanta
Atlanta, Georgia, United States, 30322
Veterans Affairs Medical Center - Atlanta (Decatur)
Decatur, Georgia, United States, 30033
United States, Illinois
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
United States, Massachusetts
Tufts - New England Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
CCOP - Kalamazoo
Kalamazoo, Michigan, United States, 49007-3731
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
United States, New Jersey
CCOP - Northern New Jersey
Hackensack, New Jersey, United States, 07601
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
United States, New York
MBCCOP-Our Lady of Mercy Cancer Center
Bronx, New York, United States, 10466
United States, North Dakota
CCOP - Merit Care Hospital
Fargo, North Dakota, United States, 58122
United States, Ohio
Ireland Cancer Center
Cleveland, Ohio, United States, 44106-5065
CCOP - Toledo Community Hospital
Toledo, Ohio, United States, 43623-3456
United States, Pennsylvania
CCOP - Geisinger Clinic and Medical Center
Danville, Pennsylvania, United States, 17822-2001
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, South Dakota
CCOP - Sioux Community Cancer Consortium
Sioux Falls, South Dakota, United States, 57104
United States, Wisconsin
CCOP - St. Vincent Hospital Cancer Center, Green Bay
Green Bay, Wisconsin, United States, 54307-3453
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226-3596
Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Study Chair: Robert S. DiPaola, MD Rutgers Cancer Institute of New Jersey
Study Chair: Robert G. Kilbourn, MD, PhD Texas Oncology, PA - San Marcos

Publications of Results:
Responsible Party: Group Chair, Eastern Cooperative Oncology Group Identifier: NCT00005847     History of Changes
Other Study ID Numbers: CDR0000067865
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: January 27, 2010
Last Verified: January 2010

Keywords provided by Eastern Cooperative Oncology Group:
adenocarcinoma of the prostate
stage IV prostate cancer
recurrent prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Sensory System Agents