Chemotherapy Plus Hormone Therapy Versus Androgen Suppression in Treating Patients With Metastatic or Unresectable Prostate Cancer

NCT ID: NCT00002855

Last Updated: 2018-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 306 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1996-08-31
• Study Completion Date: 2005-06-30

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining hormone therapy with chemotherapy and androgen suppression may kill more tumor cells. It is not yet known which treatment regimen is more effective for prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy plus hormone therapy versus androgen suppression alone as initial therapy in patients with prostate cancer that is metastatic or that cannot be removed surgically.

Detailed Description

OBJECTIVES:

• Determine the clinical benefit, as measured by time to progression and overall survival, of chemo/hormonal therapy compared to androgen ablation alone, when given as the initial systemic treatment in patients with acinar adenocarcinoma of the prostate that is not amenable to local therapy.
• Validate the clinical significance of PSA criteria for progression.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients are treated with medical or surgical castration followed by an anti-androgen therapy with either flutamide, bicalutamide, or nilutamide.
• Arm II: Patients receive chemo/hormonal therapy for 3 eight week courses, followed by total androgen blockade. Each course consists of 6 weeks of cytotoxic therapy with doxorubicin, ketoconazole, vinblastine, and estramustine followed by 2 weeks of rest. These patients are also maintained on hydrocortisone both during treatment and during rest.

Patients in arm II have a long-term central venous access device inserted.

PROJECTED ACCRUAL: A total of 368 patients will be accrued for this study.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Arm I: Medical or surgical castration followed by an anti-androgen therapy with either flutamide, bicalutamide, or nilutamide.

Group Type: EXPERIMENTAL

Bicalutamide

Intervention Type: DRUG

Flutamide

Intervention Type: DRUG

Nilutamide

Intervention Type: DRUG

Conventional Surgery

Intervention Type: PROCEDURE

Surgical castration

Arm II

Arm II: Chemo/hormonal therapy for 3 x 8-week courses, followed by total androgen blockade. Each course consists of 6 weeks of cytotoxic therapy with doxorubicin, ketoconazole, vinblastine, and estramustine followed by 2 weeks rest. Maintained on hydrocortisone both during treatment and during rest.

Group Type: EXPERIMENTAL

Doxorubicin hydrochloride

Intervention Type: DRUG

Estramustine Phosphate Sodium

Intervention Type: DRUG

Ketoconazole

Intervention Type: DRUG

Therapeutic Hydrocortisone

Intervention Type: DRUG

Vinblastine

Intervention Type: DRUG

Interventions

Bicalutamide

Intervention Type: DRUG

Doxorubicin hydrochloride

Intervention Type: DRUG

Estramustine Phosphate Sodium

Intervention Type: DRUG

Flutamide

Intervention Type: DRUG

Ketoconazole

Intervention Type: DRUG

Nilutamide

Intervention Type: DRUG

Therapeutic Hydrocortisone

Intervention Type: DRUG

Vinblastine

Intervention Type: DRUG

Conventional Surgery

Surgical castration

Intervention Type: PROCEDURE

Other Intervention Names

Casodex; Adriamycin; Adriamycin PFS; Adriamycin RDF; Rubex; Emcyt; Eulexin; Nizoral; Anandron; Nilandron; A-hydroCort; Cortef; Cortenema; Cortifoam; Hydrocortone; Solu-Cortef; Velban; Castration

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically proven acinar adenocarcinoma of the prostate
• Metastatic or locally advanced disease that either is not appropriately treated with surgery or radiation, or has recurred following previous "definitive" local therapy
• No CNS metastases
• No histologic subtypes, such as pure ductal or any component of small cell carcinoma
• Elevated PSA (at least 1.0 ng/mL in patients with prior prostatectomy or 4.0 ng/mL in those with prostate in place)

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• Zubrod 0-2

Life expectancy:

• At least 3 years

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Conjugated bilirubin no greater than 0.8 mg/dL or total bilirubin no greater than 1.5 mg/dL
• Transaminase no greater than 4 times upper limit of normal

Renal:

• Creatinine clearance at least 40 mL/min

Cardiovascular:

• No evidence of bifascicular block on EKG
• No evidence of active ischemia on EKG
• No prior history of transient ischemic attack
• No evidence of congestive heart failure

Other:

• No active peptic ulcer disease
• No regular use of antacid or H2 blockers
• No known or predicted achlorhydria
• No concurrent use of terfenadine, astemizole, omeprazole, or cisapride
• No second malignancy unless curatively treated
• No history of deep venous thrombosis
• No history of pulmonary embolism
• No serious co-morbidity
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior cytotoxic systemic therapy

Endocrine therapy:

• Prior androgen deprivation therapy allowed if given for no more than 6 months to downstage primary
• No androgen deprivation therapy within 1 year prior to study

Radiotherapy:

• No prior cytotoxic systemic therapy (including systemic strontium-89 irradiation)
• Prior definitive radiotherapy to the prostate and/or one metastatic site allowed
• At least 8 weeks since radiotherapy to the pelvis
• At least 3 weeks since radiotherapy to a single metastatic site

Surgery:

• Prior prostatectomy allowed

Other:

• No concurrent anti-anginal therapy or aggressive anticoagulants

• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Randall E. Millikan, MD, PhD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Locations

University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Millikan RE, Wen S, Pagliaro LC, Brown MA, Moomey B, Do KA, Logothetis CJ. Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer. J Clin Oncol. 2008 Dec 20;26(36):5936-42. doi: 10.1200/JCO.2007.15.9830. Epub 2008 Nov 24.

Reference Type: RESULT

PMID: 19029421 (View on PubMed)

Related Links

http://www.mdanderson.org

UT MD Anderson Cancer Center Website

Other Identifiers

P30CA016672

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MDA-DM-95231

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-G96-1044

Identifier Type: -

Identifier Source: secondary_id

CDR0000065105

Identifier Type: REGISTRY

Identifier Source: secondary_id

DM95-231

Identifier Type: -

Identifier Source: org_study_id