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

Prostate Cancer Clinical Trial

Official title:

Adjuvant 3DCRT/IMRT in Combination With Androgen Suppression and Docetaxel for High Risk Prostate Cancer Patients Post-Prostatectomy: A Phase II Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00528866
• Other study ID #: RTOG-0621
• Secondary ID: CDR0000563917NCI
• Status: Completed
• Phase: Phase 2
• Start date: April 2008
• Est. completion date: May 14, 2018

Study information

• Verified date: May 2018
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: May 14, 2018
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• bicalutamide
50 mg (one tablet) daily orally for 6 months, starting within 6 months after registration
• docetaxel
75 mg/m2 IV over 1 hour on day 1 of each cycle q21 days for 6 cycles, starting 3-6 weeks after completion of radiation therapy
• flutamide
250 mg (two 125-mg capsules) three times daily (total 750 mg) orally for 6 months, starting within 6 months after registration
• LHRH agonist
LHRH agonist (such as leuprolide, goserelin, buserelin, or triptorelin) for 6 months, starting within 6 weeks after registration

Radiation:
• 3-dimensional conformal radiation therapy

• radiation therapy
66.6 Gy (1.8 Gy per fraction, 5 days per week) to the prostate bed (IMRT or 3DCRT), starting 8 weeks after start of hormones

Locations

Country	Name	City	State
Canada	McGill Cancer Centre at McGill University	Montreal	Quebec
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana
United States	Mission Hospitals - Memorial Campus	Asheville	North Carolina
United States	Auburn Radiation Oncology	Auburn	California
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Barberton Citizens Hospital	Barberton	Ohio
United States	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana
United States	St. Luke's Cancer Network at St. Luke's Hospital	Bethlehem	Pennsylvania
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Radiation Oncology Centers - Cameron Park	Cameron Park	California
United States	Cancer Institute of Cape Girardeau, LLC	Cape Girardeau	Missouri
United States	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Urology Center of Colorado	Denver	Colorado
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Delaware County Regional Cancer Center at Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Hudner Oncology Center at Saint Anne's Hospital - Fall River	Fall River	Massachusetts
United States	Poudre Valley Radiation Oncology	Fort Collins	Colorado
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Fox Chase Cancer Center Buckingham	Furlong	Pennsylvania
United States	Wayne Radiation Oncology	Goldsboro	North Carolina
United States	Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Nevada Cancer Institute	Las Vegas	Nevada
United States	Norton Suburban Hospital	Louisville	Kentucky
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey
United States	Community Memorial Hospital Cancer Care Center	Menomonee Falls	Wisconsin
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Integris Oncology Services	Oklahoma City	Oklahoma
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center CCOP Research Base	Philadelphia	Pennsylvania
United States	Arizona Oncology Services Foundation	Phoenix	Arizona
United States	University Medical Center at Princeton	Princeton	New Jersey
United States	Cancer Centers of North Carolina - Raleigh	Raleigh	North Carolina
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	Radiation Oncology Center - Roseville	Roseville	California
United States	Mercy General Hospital	Sacramento	California
United States	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California
United States	CentraCare Clinic - River Campus	Saint Cloud	Minnesota
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Cancer Care Center, Incorporated	Salem	Ohio
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Institute at St. John's Hospital	Springfield	Illinois
United States	Crozer-Chester Medical Center	Upland	Pennsylvania
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Solano Radiation Oncology Center	Vacaville	California
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Precision Radiotherapy at University Pointe	West Chester	Ohio
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	Cancer Treatment Center	Wooster	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Free From Progression at 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.	From registration to 3 years.
Secondary	Local-regional Progression (3 Year Rate)	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.	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.)
Secondary	Distant Metastasis (3-year Rate)	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.	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.)
Secondary	Prostate Cancer Death (3-year Rate)	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.	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.)
Secondary	Non-prostate Cancer Death (3-year Rate)	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.	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.)
Secondary	Overall Survival (3-year Rate)	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.	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.)
Secondary	Time to Biochemical (PSA) Failure (3-year Rate)	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.	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.)
Secondary	Number of Patients With "Acute" Adverse Events (Based on CTCAE, v3.0)	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.	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.
Secondary	Time to "Late" Grade 3+ Adverse Events (Based on CTCAE, v3.0)	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.	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.)
Secondary	Prognostic Value of Genomic and Proteomic Markers for the Primary and Secondary Clinical Endpoints		Analysis can occur at the same time as the primary endpoint if data is available.