Clinical trial NCT00528866: Radiation Therapy, Androgen Suppression, and Docetaxel in Treating Patients With High-Risk Prostate Cancer Who Have Undergone Radical Prostatectomy
Official title: Adjuvant 3DCRT/IMRT in Combination With Androgen Suppression and Docetaxel for High Risk Prostate Cancer Patients Post-Prostatectomy: A Phase II Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
stage IV prostate cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NRG Oncology
First posted: 2007-09-12
Enrollment: 80
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Pathologically proven adenocarcinoma of the prostate gland meeting one of the following criteria:

  * Gleason ≥ 7and post-operative PSA nadir \> 0.2 ng/ml with any pathologic tumor (pT) classification
  * Gleason ≥ 8, post-operative PSA nadir ≤ 0.2 ng/ml and ≥ pT3a classification
* Must have undergone radical prostatectomy within the past year
* PSA must be obtained within 6 weeks (42 days) prior to study registration
* No lymph node or distant metastases (N0, M0), based upon the following minimum diagnostic workup:

  * History and physical examination within 8 weeks prior to study registration
  * Bone scan and CT or MRI of the pelvis and no evidence of osseous metastases on bone scan within 16 weeks prior to study registration
* No pelvic lymph nodes \> 1.5 cm in greatest dimension on CT scan or MRI of the pelvis within 16 weeks prior to study registration, unless the enlarged lymph node is biopsied and negative

PATIENT CHARACTERISTICS:

* Zubrod performance status 0-1
* Absolute neutrophil count (ANC) ≥ 2,000/mm³
* Platelet count ≥ 100,000/mm³
* Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve hemoglobin ≥ 8.0 g/dL is acceptable)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 times upper limit of normal (ULN)
* Alkaline phosphatase ≤ 2.5 times ULN
* Total bilirubin ≤ 1.2 times ULN
* No other invasive malignancy within the past 3 years except non-melanomatous skin cancer
* No active, severe co-morbidity, including any of the following:

  * Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
  * Transmural myocardial infarction within the past 6 months
  * Acute bacterial or fungal infection requiring intravenous antibiotics
  * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy
  * AIDS

    * HIV testing is not required for study entry
* No prior allergic reaction to the study drug(s)

PRIOR CONCURRENT THERAPY:

* No prior systemic chemotherapy for prostate cancer
* More than 3 years since prior chemotherapy for a different cancer
* No prior androgen deprivation for treatment of prostate cancer

  * Prior use of hormonal agents, such as finasteride or dutasteride, for treatment of benign prostatic hypertrophy is allowed
* No prior radiotherapy to the region of the prostate that would result in overlap of radiotherapy fields

Primary outcomes:
measure: Number of Participants Free From Progression at 3 Years
timeFrame: From registration to 3 years.
Secondary outcomes:
measure: Local-regional Progression (3 Year Rate)
timeFrame: 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.)
measure: Distant Metastasis (3-year Rate)
timeFrame: 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.)
measure: Prostate Cancer Death (3-year Rate)
timeFrame: 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.)
measure: Non-prostate Cancer Death (3-year Rate)
timeFrame: 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.)
measure: Overall Survival (3-year Rate)
timeFrame: 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.)
measure: Time to Biochemical (PSA) Failure (3-year Rate)
timeFrame: 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.)
measure: Number of Patients With "Acute" Adverse Events (Based on CTCAE, v3.0)
timeFrame: 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.
measure: Time to "Late" Grade 3+ Adverse Events (Based on CTCAE, v3.0)
timeFrame: 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.)
measure: Prognostic Value of Genomic and Proteomic Markers for the Primary and Secondary Clinical Endpoints
timeFrame: Analysis can occur at the same time as the primary endpoint if data is available.
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Oncology Services Foundation
state: Arizona
city: Auburn
country: United States
facility: Auburn Radiation Oncology
state: California
city: Cameron Park
country: United States
facility: Radiation Oncology Centers - Cameron Park
state: California
city: Carmichael
country: United States
facility: Mercy Cancer Center at Mercy San Juan Medical Center
state: California
city: Roseville
country: United States
facility: Radiation Oncology Center - Roseville
state: California
city: Sacramento
country: United States
facility: Radiological Associates of Sacramento Medical Group, Incorporated
state: California
city: Sacramento
country: United States
facility: Mercy General Hospital
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Vacaville
country: United States
facility: Solano Radiation Oncology Center
state: California
city: Denver
country: United States
facility: Urology Center of Colorado
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Radiation Oncology
state: Colorado
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Springfield
country: United States
facility: Cancer Institute at St. John's Hospital
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Louisville
country: United States
facility: Norton Suburban Hospital
state: Kentucky
city: Alexandria
country: United States
facility: Tulane Cancer Center Office of Clinical Research
state: Louisiana
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center - Baton Rouge
state: Louisiana
city: New Orleans
country: United States
facility: MBCCOP - LSU Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Fall River
country: United States
facility: Hudner Oncology Center at Saint Anne's Hospital - Fall River
state: Massachusetts
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology, PA - Maplewood
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
state: Minnesota
city: Robbinsdale
country: United States
facility: Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Clinic - River Campus
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Pascagoula
country: United States
facility: Regional Cancer Center at Singing River Hospital
state: Mississippi
city: Cape Girardeau
country: United States
facility: Cancer Institute of Cape Girardeau, LLC
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Las Vegas
country: United States
facility: Nevada Cancer Institute
state: Nevada
city: Marlton
country: United States
facility: Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Princeton
country: United States
facility: University Medical Center at Princeton
state: New Jersey
city: Asheville
country: United States
facility: Mission Hospitals - Memorial Campus
state: North Carolina
city: Charlotte
country: United States
facility: Presbyterian Cancer Center at Presbyterian Hospital
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Radiation Oncology
state: North Carolina
city: Hendersonville
country: United States
facility: Pardee Memorial Hospital
state: North Carolina
city: Raleigh
country: United States
facility: Cancer Centers of North Carolina - Raleigh
state: North Carolina
city: Winston-Salem
country: United States
facility: Forsyth Regional Cancer Center at Forsyth Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Barberton
country: United States
facility: Barberton Citizens Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Salem
country: United States
facility: Cancer Care Center, Incorporated
state: Ohio
city: West Chester
country: United States
facility: Precision Radiotherapy at University Pointe
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Cancer Institute
state: Oklahoma
city: Oklahoma City
country: United States
facility: Integris Oncology Services
state: Oklahoma
city: Bethlehem
country: United States
facility: St. Luke's Cancer Network at St. Luke's Hospital
state: Pennsylvania
city: Drexel Hill
country: United States
facility: Delaware County Regional Cancer Center at Delaware County Memorial Hospital
state: Pennsylvania
city: Furlong
country: United States
facility: Fox Chase Cancer Center Buckingham
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center CCOP Research Base
state: Pennsylvania
city: Upland
country: United States
facility: Crozer-Chester Medical Center
state: Pennsylvania
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Murray
country: United States
facility: Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
state: Utah
city: Seattle
country: United States
facility: CCOP - Virginia Mason Research Center
state: Washington
city: Menomonee Falls
country: United States
facility: Community Memorial Hospital Cancer Care Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Montreal
country: Canada
facility: McGill Cancer Centre at McGill University
state: Quebec
Study officials:
affiliation: Thomas Jefferson University and Hospitals
name: Mark Hurwitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dana-Farber Cancer Institute
name: Oliver Sartor, MD
role: STUDY_CHAIR
affiliation: Bodine Center for Cancer Treatment at Thomas Jefferson University Hospital
name: Ying Xiao, PhD
role: STUDY_CHAIR
References: