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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

Phase 2
18 Years
Not Enrolling
Prostate Cancer

Thank you

Trial Information

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


- 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

- 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

- 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.

Inclusion Criteria


- 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

- 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

- No concurrent prolonged exposure to sunlight

- No concurrent alcohol consumption


Biologic therapy:

- Not specified


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

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

- 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)

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Principal Investigator

Robert S. DiPaola, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Cancer Institute of New Jersey


United States: Food and Drug Administration

Study ID:




Start Date:

January 2001

Completion Date:

Related Keywords:

  • Prostate Cancer
  • adenocarcinoma of the prostate
  • stage IV prostate cancer
  • recurrent prostate cancer
  • Prostatic Neoplasms



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Ireland Cancer Center Cleveland, Ohio  44106-5065
Fox Chase Cancer Center Philadelphia, Pennsylvania  19111
Veterans Affairs Medical Center - Atlanta (Decatur) Decatur, Georgia  30033
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CCOP - Kalamazoo Kalamazoo, Michigan  49007-3731
CCOP - Metro-Minnesota Saint Louis Park, Minnesota  55416
CCOP - Northern New Jersey Hackensack, New Jersey  07601
Medical College of Wisconsin Cancer Center Milwaukee, Wisconsin  53226
CCOP - Merit Care Hospital Fargo, North Dakota  58122
CCOP - Sioux Community Cancer Consortium Sioux Falls, South Dakota  57105-1080
CCOP - Geisinger Clinic and Medical Center Danville, Pennsylvania  17822-2001
CCOP - St. Vincent Hospital Cancer Center, Green Bay Green Bay, Wisconsin  54301
Cancer Institute of New Jersey New Brunswick, New Jersey  08901
CCOP - Colorado Cancer Research Program, Incorporated Denver, Colorado  80224
Tufts - New England Medical Center Boston, Massachusetts  02111
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MBCCOP-Our Lady of Mercy Cancer Center Bronx, New York  10466