S9916, Combination Therapy in Treating Patients With Advanced Prostate Cancer That Has Not Responded to Hormone Therapy

This study has been completed.
Sponsor:
Collaborators:
Cancer and Leukemia Group B
North Central Cancer Treatment Group
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00004001
First received: November 1, 1999
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

RATIONALE: Drugs used in chemotherapy and hormone therapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving drugs in different ways may kill more tumor cells. It is not yet known whether estramustine plus docetaxel is more effective than mitoxantrone plus prednisone for prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of estramustine plus docetaxel with that of mitoxantrone plus prednisone in treating patients who have stage IV prostate cancer that has not responded to hormone therapy.


Condition Intervention Phase
Prostate Cancer
Drug: docetaxel
Drug: estramustine
Drug: mitoxantrone
Drug: prednisone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Docetaxel and Estramustine Versus Mitoxantrone and Prednisone for Advanced, Hormone Refractory Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Compare overall survival in the two study arms [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
    Measured from date of registration to date of death due to any cause


Secondary Outcome Measures:
  • Compare progression-free survival between two study arms [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
    Measured from date of registration to date of first observation of progression disease, or death due to any cause

  • Compare Prostate-Specific Antigen (PSA) response between two study arms [ Time Frame: up to 4 years or time of disease progression ] [ Designated as safety issue: No ]
    A confirmed partial response of non-measurable disease was defined as a reduction by more than 50% over baseline in two or more Prostate-Specific Antigen (PSA) measurements obtained at least four weeks apart, with no evidence of disease progression on imaging. Progressive disease was defined as a 25% increase in the serum PSA level — to at least 5 ng per milliliter — over the last preregistration measurement, with confirmation of the increase at least four weeks later. For patients with a decrease in serum PSA levels during the trial, progressive disease was defined as a confirmed increase of 25%, to at least 5 ng per milliliter over the nadir.

  • Compare objective responses between two study arms [ Time Frame: up to 12 cycles of treatment ( 1cycle = 21 days) ] [ Designated as safety issue: No ]
    Objective responses were defined on the basis of the sum of bi-dimensional measurements of metastatic lesions. Confirmed objective responses required a follow-up scan (a minimum of four weeks later) that demonstrated a continued response. Progression was defined by one of the following: a 50 percent increase or an increase of 10 cm^2, whichever was smaller, in the sum of measurements of metastatic lesions over the sum at baseline; a clear worsening of nonmeasurable disease; reappearance of any lesion that had disappeared; appearance of any new lesion; or death.

  • Compare toxicities between the two study arms [ Time Frame: up to 12 cycles of treatment (1 cycle = 21 days) ] [ Designated as safety issue: Yes ]

Enrollment: 770
Study Start Date: October 1999
Study Completion Date: January 2007
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Docetaxel and Estramustine
Estramustine, 280 mg, PO, TID, Days 1-5; q 21 days Docetaxel, 60mg/m2, IV, Day 2; q 21 days
Drug: docetaxel Drug: estramustine
Active Comparator: Mitoxantrone and Prednisone
Mitoxantrone, 12 mg/m2, IV, Day 1; q 21 days Prednisone, 5 mg, PO, BID, Days 1-21; q 21 days
Drug: mitoxantrone Drug: prednisone

Detailed Description:

OBJECTIVES:

  • Compare the overall survival and progression-free survival in patients with hormone-refractory, metastatic adenocarcinoma of the prostate treated with docetaxel and estramustine vs mitoxantrone and prednisone.
  • Compare the qualitative and quantitative toxic effects of these regimens in this patient population.
  • Compare the quality of life, including palliation of metastatic bone pain and global quality of life, of patients treated with these regimens.
  • Record prostate-specific antigen values for future correlations with response and survival in patients treated with these regimens.
  • Compare the responses in patients with bidimensionally measurable disease treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease status (measurable or evaluable disease progression vs rising PSA only), NCI Common Toxicity Criteria version 2.X pain scale (grade 2 or greater vs less than 2), and SWOG performance status (0-1 vs 2-3). Patients are randomized to one of two treatment arms.

  • Arm I: Patients receive oral estramustine 3 times daily on days 1-5 and docetaxel IV over 1 hour on day 2.
  • Arm II: Patients receive mitoxantrone IV over 30 minutes on day 1 and oral prednisone twice daily on days 1-21.

Treatment in both arms repeats every 3 weeks for a maximum of 12 courses in the absence of unacceptable toxicity or disease progression.

Quality of life is assessed at baseline, after courses 4 and 8, and then at 1 year after randomization.

Patients are followed every 6 months for 2 years and then annually for 1 year.

PROJECTED ACCRUAL: A total of 620 patients (310 per arm) will be accrued for this study within 3.5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed metastatic adenocarcinoma of the prostate
  • Unresponsive or refractory to hormonal therapy, as defined by at least 1 of the following criteria:

    • Progression of bidimensionally measurable disease
    • Progression of evaluable but not measurable disease (bone scan)
    • At least 2 consecutive rises in PSA and a PSA level of at least 5 ng/mL
  • No minimum PSA required for measurable disease or non-PSA evaluable disease
  • Soft tissue disease that has been irradiated within the past 2 months is not considered measurable disease
  • Prior orchiectomy OR
  • Medical castration using leuprolide or goserelin

    • Luteinizing hormone-releasing hormone (LHRH) agonist therapy must continue during study
  • Prior nonsteroidal antiandrogens (flutamide, ketoconazole, bicalutamide, or nilutamide) allowed if disease progression occurred
  • No third-space fluid accumulation such as ascites or symptomatic pleural effusion
  • No brain metastases

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • SWOG 0-3
  • Performance status 3 must be due to pain secondary to bone metastases

Life expectancy:

  • Not specified

Hematopoietic:

  • No hypercoagulability

Hepatic:

  • Not specified

Renal:

  • Creatinine no greater than 2.0 mg/dL

Cardiovascular:

  • No history of myocardial infarction
  • No history of congestive heart failure unless well controlled
  • No history of cerebrovascular accident or atrial fibrillation
  • No active thrombophlebitis
  • Left ventricular ejection fraction (LVEF) at least 50% by Multi Gated Acquisition Scan (MUGA) scan or 2-D echocardiogram

Pulmonary:

  • No history of pulmonary embolus

Other:

  • Recovered from major infections
  • No other significant active medical illness
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 4 weeks since prior biologic therapy and recovered
  • No more than 1 prior biologic therapy regimen
  • No concurrent biological response modifiers

Chemotherapy:

  • At least 4 weeks since prior chemotherapy and recovered
  • No more than 1 prior chemotherapy regimen
  • No prior estramustine, taxanes, anthracyclines, or mitoxantrone
  • No other concurrent chemotherapy

Endocrine therapy:

  • See Disease Characteristics
  • At least 4 weeks since prior flutamide or ketoconazole (6 weeks for bicalutamide or nilutamide)
  • No concurrent corticosteroids or hormonal therapy (except megestrol for hot flashes or continuing LHRH treatment)

Radiotherapy:

  • See Disease Characteristics
  • Prior samarium Sm 153 lexidronam pentasodium allowed
  • At least 4 weeks since prior radiotherapy and recovered
  • No prior radiotherapy to 30% or more of bone marrow
  • No prior strontium chloride Sr 89
  • No concurrent radiotherapy

Surgery:

  • See Disease Characteristics
  • At least 3 weeks since prior surgery and recovered

Other:

  • At least 4 weeks since prior bisphosphonates
  • No prior anticoagulation therapy (i.e., warfarin), except aspirin
  • No concurrent bisphosphonates
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004001

Locations
United States, Arizona
CCOP - Scottsdale Oncology Program
Scottsdale, Arizona, United States, 85259-5404
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Illinois
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States, 61602
CCOP - Carle Cancer Center
Urbana, Illinois, United States, 61801
United States, Iowa
CCOP - Cedar Rapids Oncology Project
Cedar Rapids, Iowa, United States, 52403-1206
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 50309-1016
Siouxland Hematology-Oncology
Sioux City, Iowa, United States, 51101-1733
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
CentraCare Health Plaza
Saint Cloud, Minnesota, United States, 56303
United States, Nebraska
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106
United States, North Dakota
Medcenter One Health System
Bismarck, North Dakota, United States, 58501
CCOP - Merit Care Hospital
Fargo, North Dakota, United States, 58122
Altru Health System
Grand Forks, North Dakota, United States, 58201
United States, Pennsylvania
CCOP - Geisinger Clinic and Medical Center
Danville, Pennsylvania, United States, 17822-2001
United States, South Dakota
Rapid City Regional Hospital
Rapid City, South Dakota, United States, 57709
CCOP - Sioux Community Cancer Consortium
Sioux Falls, South Dakota, United States, 57104
Sponsors and Collaborators
Southwest Oncology Group
Cancer and Leukemia Group B
North Central Cancer Treatment Group
Investigators
Study Chair: Daniel P. Petrylak, MD Herbert Irving Comprehensive Cancer Center
Study Chair: Eric J. Small, MD University of California, San Francisco
Study Chair: Patrick A. Burch, MD Mayo Clinic
  More Information

Additional Information:
Publications:
Berry DL, Moinpour CM, Jiang C, et al.: Quality of life (QOL) and pain in advanced stage prostate cancer: impact of missing data on evaluating palliation in SWOG 9916. [Abstract] J Clin Oncol 22 (Suppl 14): A-4579, 401s, 2004.
Crawford ED, Pauler DK, Tangen CM, et al.: Three-month change in PSA as a surrogate endpoint for mortality in advanced hormone-refractory prostate cancer (HRPC): data from Southwest Oncology Group study S9916. [Abstract] J Clin Oncol 22 (Suppl 14): A-4505, 383s, 2004.
Petrylak DP, Tangen C, Hussain M, et al.: SWOG 99-16: randomized phase III trial of docetaxel (D)/estramustine (E) versus mitoxantrone(M)/prednisone(p) in men with androgen-independent prostate cancer (AIPCA). [Abstract] J Clin Oncol 22 (Suppl 14): A-3, 2s, 2004.
Goldman B, Hussain M, Tangen C, et al.: Prostate-specific antigen progression (PSA-P) as a predictor of overall survival (OS) in patients (pts) with metastatic prostate cancer (PC): data from S9346 and S9916. [Abstract] American Society of Clinical Oncology 2008 Genitourinary Cancers Symposium, Feb 14-16, 2008, San Francisco, CA. A-165, 2008.
Hussain MH, Goldman B, Tangen CM, et al.: Use of prostate-specific antigen progression (PSA-P) to predict overall survival (OS) in patients (pts) with metastatic prostate cancer (PC): data from S9346 and S9916. [Abstract] J Clin Oncol 26 (Suppl 15): A-5015, 2008.

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00004001     History of Changes
Other Study ID Numbers: CDR0000067211, S9916, U10CA032102
Study First Received: November 1, 1999
Last Updated: February 21, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Docetaxel
Estramustine
Mitoxantrone
Prednisone
Alkylating Agents
Analgesics
Anti-Inflammatory Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Central Nervous System Agents
Enzyme Inhibitors
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014