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Radiation Therapy, Androgen Suppression, and Docetaxel in Treating Patients With High-Risk Prostate Cancer Who Have Undergone Radical Prostatectomy

Phase 2
Completed
Conditions
Prostate Cancer
Interventions
Drug: LHRH agonist
Radiation: 3-dimensional conformal radiation therapy
Radiation: radiation therapy
Registration Number
NCT00528866
Lead Sponsor
Radiation Therapy Oncology Group
Brief Summary

RATIONALE: Specialized radiation therapy that delivers a high-dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as leuprolide, goserelin, flutamide, or bicalutamide, may lessen the amount of androgens made by the body. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with androgen suppression and docetaxel after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well giving radiation therapy together with androgen suppression and docetaxel works in treating patients with high risk prostate cancer who have undergone radical prostatectomy.

Detailed Description

OBJECTIVES:

Primary

* To assess whether the addition of androgen suppression therapy and docetaxel to adjuvant radiotherapy improves freedom from progression.

Secondary

* To assess freedom from local-regional progression, distant metastases, disease-free survival, prostate cancer specific survival, non-prostate cancer specific survival, overall survival, and time to biochemical (PSA) failure.

* To evaluate treatment-related "acute" and "late" toxicity based on Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0.

* To correlate genomic and proteomic biomarkers with the primary and secondary clinical endpoints utilizing archival prostatectomy tissue and pretreatment and prospectively collected serum/plasma.

OUTLINE: This is a multicenter study.

* Androgen suppression therapy: Patients receive a luteinizing hormone-releasing hormone (LHRH) agonist (leuprolide or goserelin) as an injection AND an oral antiandrogen (flutamide 3 times daily or bicalutamide once daily) for up to 6 months.

* Radiotherapy: Beginning 8 weeks after the initiation of androgen suppression therapy, patients undergo 3-dimensional conformal radiotherapy or intensity-modulated radiotherapy once a day 5 days a week for up to approximately 8 weeks.

* Chemotherapy: Beginning 3-6 weeks after the completion of radiotherapy, patients receive docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for up to 6 courses.

After the completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
80
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Androgen suppression + RT + docetaxel3-dimensional conformal radiation therapyLHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Androgen suppression + RT + docetaxelradiation therapyLHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Androgen suppression + RT + docetaxelbicalutamideLHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Androgen suppression + RT + docetaxelLHRH agonistLHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Androgen suppression + RT + docetaxeldocetaxelLHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Androgen suppression + RT + docetaxelflutamideLHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Primary Outcome Measures
NameTimeMethod
Number of Participants Free From Progression at 3 YearsFrom registration to 3 years.

Failure was defined as PSA ≥ 0.4 ng/mL after the end of radiation therapy confirmed by a second higher PSA, non-protocol hormones, local-regional progression, distant metastasis, or death, within 3 years after study registration. Freedom from progression (FFP) rate under null hypothesis was 50%; under alternative hypothesis ≥ 70%. Per Fleming's multiple testing procedure with 3 stages, 69 patients (76 allowing for 10% ineligible) were required for 90% power and type I error 0.025. If ≥ 44 of 69 patients had a FFP event, we would reject 50% FFP rate in favor of ≥ 70%. Analysis was out of 74 patients (not 69), so ≥ 44 was revised to ≥ 46.

Secondary Outcome Measures
NameTimeMethod
Prostate Cancer Death (3-year Rate)Analysis occurs after all patients have been on study for at least 3 years. (Patients are followed from registration to death or study termination whichever occurs first.)

Time from registration to date of distant metastasis (failure), death (competing risk), or last follow-up (censored). Three-year failure rate and 95% confidence interval were estimated by the cumulative incidence method.

Overall Survival (3-year Rate)Analysis occurs after all patients have been on study for at least 3 years. (Patients are followed from registration to death or study termination whichever occurs first.)

Time from registration to date of death (failure) or last follow-up (censored). Three-year rate and 95% confidence interval were estimated by the Kaplan-Meier method.

Non-prostate Cancer Death (3-year Rate)Analysis occurs after all patients have been on study for at least 3 years. (Patients are followed from registration to death or study termination whichever occurs first.)

Time from registration to date of death due to other causes (failure), death due to prostate cancer (competing risk), or last follow-up (censored).Three-year failure rate and 95% confidence interval were estimated by the cumulative incidence method.

Local-regional Progression (3 Year Rate)Analysis occurs after all patients have been on study for at least 3 years. (Patients are followed from registration to death or study termination whichever occurs first.)

Time from registration to date of local progression (failure), death (competing risk), or last follow-up (censored). Three-year failure rate and 95% confidence interval were estimated by the cumulative incidence method.

Distant Metastasis (3-year Rate)Analysis occurs after all patients have been on study for at least 3 years. (Patients are followed from registration to death or study termination whichever occurs first.)

Time from registration to date of distant metastasis (failure), death (competing risk), or last follow-up (censored). Three-year failure rate and 95% confidence interval were estimated by the cumulative incidence method.

Time to Biochemical (PSA) Failure (3-year Rate)Analysis occurs after all patients have been on study for at least 3 years. (Patients are followed from registration to death or study termination whichever occurs first.)

Failure is defined as PSA ≥ 0.4 ng/mL confirmed by a second higher PSA or initiation of non-protocol hormones. Death is considered a competing risk. Three-year failure rate and 95% confidence interval were estimated by the cumulative incidence method.

Number of Patients With "Acute" Adverse Events (Based on CTCAE, v3.0)From start of treatment to 90 days after the planned end of treatment (21 days after last docetaxel dose). Analysis occurs at the time of the primary analysis. (Patients are followed until death or study termination whichever occurs first.

The number of patients with at least one grade 3 or higher adverse event (AE) from start of treatment to 90 days after the planned end of treatment (21 days after last docetaxel dose). Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

Time to "Late" Grade 3+ Adverse Events (Based on CTCAE, v3.0)From 91 to 730 days after the planned end of treatment (21 days after last docetaxel dose). Analysis occurs at the time of the primary analysis. (Patients are followed from registration to death or study termination whichever occurs first.)

Two-year rate shown (cumulative incidence method). Adverse events are graded using CTCAE v3.0. Time of first late adverse event occurrence of the Grade 3+ adverse event between 91 days and 730 days from the completion of treatment (3 weeks after the last planned docetaxel dose) calculated. Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.

Prognostic Value of Genomic and Proteomic Markers for the Primary and Secondary Clinical EndpointsAnalysis can occur at the same time as the primary endpoint if data is available.

Trial Locations

Locations (70)

Mary Bird Perkins Cancer Center - Baton Rouge

🇺🇸

Baton Rouge, Louisiana, United States

Mercy Cancer Center at Mercy San Juan Medical Center

🇺🇸

Carmichael, California, United States

Fox Chase Cancer Center CCOP Research Base

🇺🇸

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center - Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

🇺🇸

Spartanburg, South Carolina, United States

Greenebaum Cancer Center at University of Maryland Medical Center

🇺🇸

Baltimore, Maryland, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

CCOP - Virginia Mason Research Center

🇺🇸

Seattle, Washington, United States

Nevada Cancer Institute

🇺🇸

Las Vegas, Nevada, United States

MBCCOP - LSU Health Sciences Center

🇺🇸

New Orleans, Louisiana, United States

Mercy and Unity Cancer Center at Unity Hospital

🇺🇸

Fridley, Minnesota, United States

Solano Radiation Oncology Center

🇺🇸

Vacaville, California, United States

Tulane Cancer Center Office of Clinical Research

🇺🇸

Alexandria, Louisiana, United States

Fairview Ridges Hospital

🇺🇸

Burnsville, Minnesota, United States

Poudre Valley Radiation Oncology

🇺🇸

Fort Collins, Colorado, United States

Hudner Oncology Center at Saint Anne's Hospital - Fall River

🇺🇸

Fall River, Massachusetts, United States

Cancer Centers of North Carolina - Raleigh

🇺🇸

Raleigh, North Carolina, United States

Rapid City Regional Hospital

🇺🇸

Rapid City, South Dakota, United States

Cancer Institute at St. John's Hospital

🇺🇸

Springfield, Illinois, United States

CCOP - Ochsner

🇺🇸

New Orleans, Louisiana, United States

Mercy and Unity Cancer Center at Mercy Hospital

🇺🇸

Coon Rapids, Minnesota, United States

Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center

🇺🇸

Robbinsdale, Minnesota, United States

Presbyterian Cancer Center at Presbyterian Hospital

🇺🇸

Charlotte, North Carolina, United States

Mission Hospitals - Memorial Campus

🇺🇸

Asheville, North Carolina, United States

Fairview Southdale Hospital

🇺🇸

Edina, Minnesota, United States

Barberton Citizens Hospital

🇺🇸

Barberton, Ohio, United States

Newark Beth Israel Medical Center

🇺🇸

Newark, New Jersey, United States

Summa Center for Cancer Care at Akron City Hospital

🇺🇸

Akron, Ohio, United States

McGill Cancer Centre at McGill University

🇨🇦

Montreal, Quebec, Canada

Wayne Radiation Oncology

🇺🇸

Goldsboro, North Carolina, United States

Ridgeview Medical Center

🇺🇸

Waconia, Minnesota, United States

Crozer-Chester Medical Center

🇺🇸

Upland, Pennsylvania, United States

CCOP - Upstate Carolina

🇺🇸

Spartanburg, South Carolina, United States

Cancer Treatment Center

🇺🇸

Wooster, Ohio, United States

Pardee Memorial Hospital

🇺🇸

Hendersonville, North Carolina, United States

Community Memorial Hospital Cancer Care Center

🇺🇸

Menomonee Falls, Wisconsin, United States

Fox Chase Cancer Center Buckingham

🇺🇸

Furlong, Pennsylvania, United States

Charles M. Barrett Cancer Center at University Hospital

🇺🇸

Cincinnati, Ohio, United States

CCOP - Metro-Minnesota

🇺🇸

Saint Louis Park, Minnesota, United States

UCSF Helen Diller Family Comprehensive Cancer Center

🇺🇸

San Francisco, California, United States

Radiation Oncology Centers - Cameron Park

🇺🇸

Cameron Park, California, United States

Auburn Radiation Oncology

🇺🇸

Auburn, California, United States

Radiation Oncology Center - Roseville

🇺🇸

Roseville, California, United States

CCOP - Carle Cancer Center

🇺🇸

Urbana, Illinois, United States

CCOP - Christiana Care Health Services

🇺🇸

Newark, Delaware, United States

Minnesota Oncology Hematology, PA - Maplewood

🇺🇸

Maplewood, Minnesota, United States

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

🇺🇸

Minneapolis, Minnesota, United States

CentraCare Clinic - River Campus

🇺🇸

Saint Cloud, Minnesota, United States

United Hospital

🇺🇸

Saint Paul, Minnesota, United States

Regional Cancer Center at Singing River Hospital

🇺🇸

Pascagoula, Mississippi, United States

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

🇺🇸

Saint Louis, Missouri, United States

University Medical Center at Princeton

🇺🇸

Princeton, New Jersey, United States

Cancer Institute of Cape Girardeau, LLC

🇺🇸

Cape Girardeau, Missouri, United States

Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton

🇺🇸

Marlton, New Jersey, United States

Cancer Care Center, Incorporated

🇺🇸

Salem, Ohio, United States

Precision Radiotherapy at University Pointe

🇺🇸

West Chester, Ohio, United States

St. Luke's Cancer Network at St. Luke's Hospital

🇺🇸

Bethlehem, Pennsylvania, United States

Delaware County Regional Cancer Center at Delaware County Memorial Hospital

🇺🇸

Drexel Hill, Pennsylvania, United States

Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

🇺🇸

Murray, Utah, United States

Arizona Oncology Services Foundation

🇺🇸

Phoenix, Arizona, United States

Mercy General Hospital

🇺🇸

Sacramento, California, United States

Radiological Associates of Sacramento Medical Group, Incorporated

🇺🇸

Sacramento, California, United States

Urology Center of Colorado

🇺🇸

Denver, Colorado, United States

Josephine Ford Cancer Center at Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

Forsyth Regional Cancer Center at Forsyth Medical Center

🇺🇸

Winston-Salem, North Carolina, United States

Wake Forest University Comprehensive Cancer Center

🇺🇸

Winston-Salem, North Carolina, United States

Oklahoma University Cancer Institute

🇺🇸

Oklahoma City, Oklahoma, United States

Integris Oncology Services

🇺🇸

Oklahoma City, Oklahoma, United States

Medical College of Wisconsin Cancer Center

🇺🇸

Milwaukee, Wisconsin, United States

Norton Suburban Hospital

🇺🇸

Louisville, Kentucky, United States

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