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S0421, Docetaxel and Prednisone With or Without Atrasentan in Treating Patients With Stage IV Prostate Cancer and Bone Metastases That Did Not Respond to Previous Hormone Therapy

Phase 3
Completed
Conditions
Prostate Cancer
Metastatic Cancer
Interventions
Registration Number
NCT00134056
Lead Sponsor
SWOG Cancer Research Network
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel, prednisone, and atrasentan work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether docetaxel, prednisone, and atrasentan are more effective than docetaxel and prednisone in treating prostate cancer.

PURPOSE: This randomized phase III trial is studying docetaxel, prednisone, and atrasentan to see how well they work compared to docetaxel and prednisone in treating patients with stage IV prostate cancer and bone metastases that did not respond to previous hormone therapy.

Detailed Description

OBJECTIVES:

Primary

* Compare the survival and progression-free survival of patients with hormone-refractory stage IV prostate cancer and bone metastases treated with docetaxel and prednisone combined with either atrasentan vs placebo.

Secondary

* Compare pain progression of patients treated with these regimens.

* Compare the qualitative and quantitative toxicity of these regimens in these patients.

* Compare the quality of life, in terms of palliation of metastatic bone pain and improvement in functional status, of patients treated with these regimens.

* Compare prostate-specific antigen (PSA) response rates in patients treated with these regimens.

* Compare objective response in patients with measurable disease treated with these regimens.

* Determine whether a 30% reduction in PSA and the slope of PSA from baseline to 3 months is a surrogate marker for survival in patients treated with these regimens.

* Correlate PSA progression with clinical progression and death in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to disease progression (measurable or non-measurable disease progression vs prostate-specific antigen progression only), use of bisphosphonates at study entry (yes vs no), worst pain, measured by the Brief Pain Inventory "pain" scale (\< grade 4 vs ≥ grade 4), and extraskeletal metastases (yes vs no). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks in the absence of disease progression\* or unacceptable toxicity.

* Arm II: Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks in the absence of disease progression\* or unacceptable toxicity.

NOTE: \*Patients with PSA progression alone will be allowed to continue treatment

Quality of life is assessed at baseline, before courses 4, 7, and 10, and then after completion of study treatment.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for up to 3 years from study entry.

PROJECTED ACCRUAL: A total of 930 patients will be accrued for this study within 4 years.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
1038
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm II: atrasentan hydrochlorideatrasentan hydrochloridePatients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.
Arm I: placeboplaceboPatients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.
Arm I: placebodocetaxelPatients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.
Arm I: placeboprednisonePatients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.
Arm II: atrasentan hydrochloridedocetaxelPatients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.
Arm II: atrasentan hydrochlorideprednisonePatients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.
Primary Outcome Measures
NameTimeMethod
Compare Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer.Up to 7 years after study opens

Measured from date of registration to date of death due to any cause. Patient last known to be alive are censored at date of last contact.

Compare Progression-free Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer.Up to 7 years after study opens

Measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients without progression are censored at date of last contact. Disease progression is defined by confirmed bone disease progression, soft tissue or pain progression.

Secondary Outcome Measures
NameTimeMethod
Compare Pain Progression Between the Two Study Arms.Up to 52 weeks

Pain progression is defined as patients reporting an increase of at least two Worst Pain points, maintained for at least two consecutive assessments, increase to Level 3 (strong opioid) on the Pain Medication Log Analgesic Code for patients receiving Level 2 (weak opioid) analgesics at randomization, or an increase to Level 2 or 3 analgesics for patients receiving Level 0 or 1 analgesics at randomization.

Compare Qualitative and Quantitative Toxicity Between the Two Study ArmsAssessed every 3 weeks up to 52 weeks

Only adverse events that are possibly, probably or definitely related to study drug are reported.

Compare Prostate Specific Antigen (PSA) Response Rates Between the Experimental Arm and the Standard Arm.Up to 7 years after study opens

PSA Partial Response: Greater than or equal to 50% reduction in baseline PSA. There must be no evidence of soft tissue progression, or confirmed none disease progression, or pain progression.

Compare Objective Responses Between the Two Treatment Groups in Patients With Measurable Disease as Defined by RECIST Criteria.Up to 52 weeks

Complete Response (CR): Complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. Normalization of markers and other abnormal lab values. PSA ≤ .2 ng/ml. Partial Response (PR): Applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions.

Trial Locations

Locations (553)

Providence Cancer Center at Providence Hospital

🇺🇸

Mobile, Alabama, United States

Alaska Regional Hospital Cancer Center

🇺🇸

Anchorage, Alaska, United States

Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital

🇺🇸

Fairbanks, Alaska, United States

Mayo Clinic Scottsdale

🇺🇸

Scottsdale, Arizona, United States

Arizona Cancer Center at University of Arizona Health Sciences Center

🇺🇸

Tucson, Arizona, United States

Hembree Mercy Cancer Center at St. Edward Mercy Medical Center

🇺🇸

Fort Smith, Arkansas, United States

East Bay Radiation Oncology Center

🇺🇸

Castro Valley, California, United States

Eden Medical Center

🇺🇸

Castro Valley, California, United States

Valley Medical Oncology Consultants - Castro Valley

🇺🇸

Castro Valley, California, United States

Valley Medical Oncology

🇺🇸

Fremont, California, United States

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Providence Cancer Center at Providence Hospital
🇺🇸Mobile, Alabama, United States

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