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

Sponsor

Eastern Cooperative Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00005847

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Study Details

Study Description

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

OBJECTIVES:

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 Design

Study Type:

Interventional

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 :

Jan 1, 2001

Actual Primary Completion Date :

Jul 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

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

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

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

Hepatic:

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

Renal:

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

Cardiovascular:

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

Other:

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

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

Radiotherapy:

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

Surgery:

See Disease Characteristics

Other:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CCOP - Colorado Cancer Research Program, Incorporated	Denver	Colorado	United States	80224
2	Emory University Hospital - Atlanta	Atlanta	Georgia	United States	30322
3	Veterans Affairs Medical Center - Atlanta (Decatur)	Decatur	Georgia	United States	30033
4	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
5	Tufts - New England Medical Center	Boston	Massachusetts	United States	02111
6	CCOP - Kalamazoo	Kalamazoo	Michigan	United States	49007-3731
7	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
8	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
9	CCOP - Northern New Jersey	Hackensack	New Jersey	United States	07601
10	Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
11	MBCCOP-Our Lady of Mercy Cancer Center	Bronx	New York	United States	10466
12	CCOP - Merit Care Hospital	Fargo	North Dakota	United States	58122
13	Ireland Cancer Center	Cleveland	Ohio	United States	44106-5065
14	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43623-3456
15	CCOP - Geisinger Clinic and Medical Center	Danville	Pennsylvania	United States	17822-2001
16	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
17	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota	United States	57104
18	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin	United States	54307-3453
19	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226-3596