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

• Sponsor: Radiation Therapy Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00528866
• Collaborator: National Cancer Institute (NCI) (NIH), NRG Oncology (Other)
• Enrollment: 80
• Locations: 70
• Arm: 1
• Actual Duration (Months): 121.4
• Patients Per Site: 1.1
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: bicalutamide; Drug: docetaxel; Drug: flutamide; Drug: LHRH agonist; Radiation: 3-dimensional conformal radiation therapy; Radiation: radiation therapy	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Adjuvant 3DCRT/IMRT in Combination With Androgen Suppression and Docetaxel for High Risk Prostate Cancer Patients Post-Prostatectomy: A Phase II Trial
• Actual Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: May 14, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Androgen suppression + RT + docetaxel LHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel

Drug: bicalutamide; 50 mg (one tablet) daily orally for 6 months, starting within 6 months after registration; Drug: 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; Drug: flutamide; 250 mg (two 125-mg capsules) three times daily (total 750 mg) orally for 6 months, starting within 6 months after registration; Drug: 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: 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

Outcome Measures

Primary Outcome Measures

1. Number of Participants Free From Progression at 3 Years [From 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

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Services Foundation	Phoenix	Arizona	United States	85013
2	Auburn Radiation Oncology	Auburn	California	United States	95603
3	Radiation Oncology Centers - Cameron Park	Cameron Park	California	United States	95682
4	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California	United States	95608
5	Radiation Oncology Center - Roseville	Roseville	California	United States	95661
6	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California	United States	95815
7	Mercy General Hospital	Sacramento	California	United States	95819
8	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
9	Solano Radiation Oncology Center	Vacaville	California	United States	95687
10	Urology Center of Colorado	Denver	Colorado	United States	80211
11	Poudre Valley Radiation Oncology	Fort Collins	Colorado	United States	80528
12	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
13	Cancer Institute at St. John's Hospital	Springfield	Illinois	United States	62702
14	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
15	Norton Suburban Hospital	Louisville	Kentucky	United States	40207
16	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana	United States	71315-3198
17	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana	United States	70809
18	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
19	CCOP - Ochsner	New Orleans	Louisiana	United States	70121
20	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
21	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
22	Hudner Oncology Center at Saint Anne's Hospital - Fall River	Fall River	Massachusetts	United States	02721
23	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan	United States	48202
24	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
25	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
26	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
27	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
28	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
29	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
30	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
31	CentraCare Clinic - River Campus	Saint Cloud	Minnesota	United States	56303
32	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
33	United Hospital	Saint Paul	Minnesota	United States	55102
34	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
35	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi	United States	39581
36	Cancer Institute of Cape Girardeau, LLC	Cape Girardeau	Missouri	United States	63703
37	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri	United States	63110
38	Nevada Cancer Institute	Las Vegas	Nevada	United States	89135
39	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey	United States	08053
40	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
41	University Medical Center at Princeton	Princeton	New Jersey	United States	08540-3298
42	Mission Hospitals - Memorial Campus	Asheville	North Carolina	United States	28801
43	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
44	Wayne Radiation Oncology	Goldsboro	North Carolina	United States	27534
45	Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
46	Cancer Centers of North Carolina - Raleigh	Raleigh	North Carolina	United States	27607
47	Forsyth Regional Cancer Center at Forsyth Medical Center	Winston-Salem	North Carolina	United States	27103
48	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
49	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio	United States	44309-2090
50	Barberton Citizens Hospital	Barberton	Ohio	United States	44203
51	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45267
52	Cancer Care Center, Incorporated	Salem	Ohio	United States	44460
53	Precision Radiotherapy at University Pointe	West Chester	Ohio	United States	45069
54	Cancer Treatment Center	Wooster	Ohio	United States	44691
55	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma	United States	73104
56	Integris Oncology Services	Oklahoma City	Oklahoma	United States	73112
57	St. Luke's Cancer Network at St. Luke's Hospital	Bethlehem	Pennsylvania	United States	18015
58	Delaware County Regional Cancer Center at Delaware County Memorial Hospital	Drexel Hill	Pennsylvania	United States	19026
59	Fox Chase Cancer Center Buckingham	Furlong	Pennsylvania	United States	18925
60	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania	United States	19111-2497
61	Fox Chase Cancer Center CCOP Research Base	Philadelphia	Pennsylvania	United States	19140
62	Crozer-Chester Medical Center	Upland	Pennsylvania	United States	19013
63	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
64	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
65	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
66	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah	United States	84157
67	CCOP - Virginia Mason Research Center	Seattle	Washington	United States	98101
68	Community Memorial Hospital Cancer Care Center	Menomonee Falls	Wisconsin	United States	53051
69	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
70	McGill Cancer Centre at McGill University	Montreal	Quebec	Canada	H2W 1S6

Sponsors and Collaborators

• Radiation Therapy Oncology Group
• National Cancer Institute (NCI)
• NRG Oncology

Investigators

• Principal Investigator: Mark Hurwitz, MD, Thomas Jefferson University and Hospitals
• Study Chair: Oliver Sartor, MD, Dana-Farber Cancer Institute
• Study Chair: Ying Xiao, PhD, Bodine Center for Cancer Treatment at Thomas Jefferson University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT00528866
• Other Study ID Numbers: RTOG-0621; CDR0000563917; NCI-2009-00740
• First Posted: Sep 12, 2007
• Last Update Posted: Apr 24, 2019
• Last Verified: May 1, 2018

• Keywords provided by Radiation Therapy Oncology Group: adenocarcinoma of the prostate; stage IIB prostate cancer; stage IIA prostate cancer; stage III prostate cancer; stage IV prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Docetaxel; Bicalutamide; Flutamide

Study Results

Participant Flow

Arm/Group Title	Androgen Suppression + RT + Docetaxel
Arm/Group Description	Luteinizing hormone-releasing hormone (LHRH) agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Period Title: Overall Study
STARTED	80
COMPLETED	74
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Androgen Suppression + RT + Docetaxel
Arm/Group Description	LHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Overall Participants	74
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	74 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Free From Progression at 3 Years
Description	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.
Time Frame	From registration to 3 years.

Outcome Measure Data

Analysis Population Description

All eligible patients who started study treatment

Arm/Group Title	Androgen Suppression + RT + Docetaxel
Arm/Group Description	LHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Measure Participants	74
Number [participants]	54 73%

2. Secondary Outcome

Title	Local-regional Progression (3 Year Rate)
Description	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.
Time Frame	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.)

Outcome Measure Data

Analysis Population Description

All eligible patients who started study treatment

Arm/Group Title	Androgen Suppression + RT + Docetaxel
Arm/Group Description	LHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Measure Participants	74
Number (95% Confidence Interval) [percentage of participants]	0 0%

3. Secondary Outcome

Title	Distant Metastasis (3-year Rate)
Description	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 Frame	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.)

Outcome Measure Data

Analysis Population Description

All eligible patients who started study treatment

Arm/Group Title	Androgen Suppression + RT + Docetaxel
Arm/Group Description	LHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Measure Participants	74
Number (95% Confidence Interval) [percentage of participants]	6.8 9.2%

4. Secondary Outcome

Title	Prostate Cancer Death (3-year Rate)
Description	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 Frame	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.)

Outcome Measure Data

Analysis Population Description

All eligible patients who started study treatment

Arm/Group Title	Androgen Suppression + RT + Docetaxel
Arm/Group Description	LHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Measure Participants	74
Number (95% Confidence Interval) [percentage of participants]	0 0%

5. Secondary Outcome

Title	Non-prostate Cancer Death (3-year Rate)
Description	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.
Time Frame	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.)

Outcome Measure Data

Analysis Population Description

All eligible patients who started study treatment

Arm/Group Title	Androgen Suppression + RT + Docetaxel
Arm/Group Description	LHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Measure Participants	74
Number (95% Confidence Interval) [percentage of participants]	1.4 1.9%

6. Secondary Outcome

Title	Overall Survival (3-year Rate)
Description	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.
Time Frame	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.)

Outcome Measure Data

Analysis Population Description

All eligible patients who started study treatment

Arm/Group Title	Androgen Suppression + RT + Docetaxel
Arm/Group Description	LHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Measure Participants	74
Number (95% Confidence Interval) [percentage of participants]	98.6 133.2%

7. Secondary Outcome

Title	Time to Biochemical (PSA) Failure (3-year Rate)
Description	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.
Time Frame	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.)

Outcome Measure Data

Analysis Population Description

All eligible patients who started study treatment

Arm/Group Title	Androgen Suppression + RT + Docetaxel
Arm/Group Description	LHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Measure Participants	74
Number (95% Confidence Interval) [percentage of participants]	25.7 34.7%

8. Secondary Outcome

Title	Number of Patients With "Acute" Adverse Events (Based on CTCAE, v3.0)
Description	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 Frame	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.

Outcome Measure Data

Analysis Population Description

All eligible patients who started study treatment

Arm/Group Title	Androgen Suppression + RT + Docetaxel
Arm/Group Description	LHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Measure Participants	74
Number [participants]	57 77%

9. Secondary Outcome

Title	Time to "Late" Grade 3+ Adverse Events (Based on CTCAE, v3.0)
Description	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.
Time Frame	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.)

Outcome Measure Data

Analysis Population Description

All eligible patients who started study treatment

Arm/Group Title	Androgen Suppression + RT + Docetaxel
Arm/Group Description	LHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Measure Participants	74
Number (95% Confidence Interval) [percentage of participants]	8.1 10.9%

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The protocol did not provide sufficient detail to meet National Cancer Institute requirements for release of specimens from the NRG tissue bank for the protocol-specified analysis, therefore no assays were performed and no data were collected for this outcome measure. Specimen use will require federal approval and funding separate from this trial.

Arm/Group Title	Androgen Suppression + RT + Docetaxel
Arm/Group Description	Luteinizing hormone-releasing hormone (LHRH) agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
Measure Participants	0

Adverse Events

Adverse Event Reporting Description	Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Arm/Group Title	Androgen Suppression + RT + Docetaxel
Arm/Group Description	LHRH agonist and oral antiandrogen (flutamide or bicalutamide), radiation therapy (RT), and docetaxel
All Cause Mortality
	Androgen Suppression + RT + Docetaxel
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Androgen Suppression + RT + Docetaxel
	Affected / at Risk (%)	# Events
Total	20/74 (27%)
Blood and lymphatic system disorders
Febrile neutropenia	2/74 (2.7%)
Hemoglobin decreased	2/74 (2.7%)
Cardiac disorders
Ventricular fibrillation	1/74 (1.4%)
Gastrointestinal disorders
Abdominal pain	1/74 (1.4%)
Constipation	1/74 (1.4%)
Ileus	1/74 (1.4%)
Small intestinal obstruction	1/74 (1.4%)
General disorders
Chills	1/74 (1.4%)
Fatigue	1/74 (1.4%)
Infections and infestations
Sinusitis [with normal or Grade 1-2 ANC]	1/74 (1.4%)
Investigations
Creatinine increased	1/74 (1.4%)
Leukopenia	5/74 (6.8%)
Lymphopenia	4/74 (5.4%)
Neutrophil count decreased	7/74 (9.5%)
Metabolism and nutrition disorders
Dehydration	1/74 (1.4%)
Hyperglycemia	1/74 (1.4%)
Hypokalemia	1/74 (1.4%)
Hypomagnesemia	1/74 (1.4%)
Hyponatremia	1/74 (1.4%)
Musculoskeletal and connective tissue disorders
Chest wall pain	1/74 (1.4%)
Muscle weakness	1/74 (1.4%)
Nervous system disorders
Dizziness	1/74 (1.4%)
Renal and urinary disorders
Ureteric obstruction	2/74 (2.7%)
Urinary frequency	1/74 (1.4%)
Urinary retention	1/74 (1.4%)
Skin and subcutaneous tissue disorders
Alopecia	1/74 (1.4%)
Other (Not Including Serious) Adverse Events
	Androgen Suppression + RT + Docetaxel
	Affected / at Risk (%)	# Events
Total	73/74 (98.6%)
Blood and lymphatic system disorders
Hemoglobin decreased	59/74 (79.7%)
Eye disorders
Watering eyes	6/74 (8.1%)
Gastrointestinal disorders
Abdominal pain	5/74 (6.8%)
Constipation	33/74 (44.6%)
Diarrhea	51/74 (68.9%)
Dyspepsia	10/74 (13.5%)
Fecal incontinence	5/74 (6.8%)
Flatulence	5/74 (6.8%)
Gastrointestinal disorder	9/74 (12.2%)
Hemorrhoids	6/74 (8.1%)
Mucositis oral	13/74 (17.6%)
Nausea	34/74 (45.9%)
Proctitis	12/74 (16.2%)
Rectal hemorrhage	6/74 (8.1%)
Rectal pain	5/74 (6.8%)
Vomiting	12/74 (16.2%)
General disorders
Chills	7/74 (9.5%)
Edema limbs	35/74 (47.3%)
Fatigue	70/74 (94.6%)
Fever	10/74 (13.5%)
General symptom	5/74 (6.8%)
Localized edema [trunk/genital]	8/74 (10.8%)
Pain [NOS]	4/74 (5.4%)
Pain [other]	11/74 (14.9%)
Injury, poisoning and procedural complications
Dermatitis radiation	5/74 (6.8%)
Radiation recall reaction (dermatologic)	6/74 (8.1%)
Investigations
Alanine aminotransferase increased	10/74 (13.5%)
Aspartate aminotransferase increased	11/74 (14.9%)
Creatinine increased	7/74 (9.5%)
Laboratory test abnormal	9/74 (12.2%)
Leukopenia	40/74 (54.1%)
Lymphopenia	23/74 (31.1%)
Neutrophil count decreased	44/74 (59.5%)
Platelet count decreased	16/74 (21.6%)
Weight gain	12/74 (16.2%)
Weight loss	5/74 (6.8%)
Metabolism and nutrition disorders
Anorexia	15/74 (20.3%)
Dehydration	7/74 (9.5%)
Hyperglycemia	39/74 (52.7%)
Hyperkalemia	5/74 (6.8%)
Hypoalbuminemia	7/74 (9.5%)
Hypocalcemia	5/74 (6.8%)
Hypokalemia	4/74 (5.4%)
Hyponatremia	14/74 (18.9%)
Musculoskeletal and connective tissue disorders
Arthritis	4/74 (5.4%)
Back pain	15/74 (20.3%)
Bone pain	15/74 (20.3%)
Joint pain	25/74 (33.8%)
Muscle weakness	8/74 (10.8%)
Muscle weakness lower limb	4/74 (5.4%)
Musculoskeletal disorder	7/74 (9.5%)
Myalgia	16/74 (21.6%)
Pain in extremity	7/74 (9.5%)
Nervous system disorders
Dizziness	14/74 (18.9%)
Headache	11/74 (14.9%)
Memory impairment	8/74 (10.8%)
Peripheral sensory neuropathy	49/74 (66.2%)
Taste alteration	29/74 (39.2%)
Psychiatric disorders
Agitation	4/74 (5.4%)
Anxiety	8/74 (10.8%)
Depression	12/74 (16.2%)
Insomnia	19/74 (25.7%)
Libido decreased	10/74 (13.5%)
Renal and urinary disorders
Bladder pain	4/74 (5.4%)
Cystitis	13/74 (17.6%)
Urethral pain	7/74 (9.5%)
Urinary frequency	56/74 (75.7%)
Urinary incontinence	42/74 (56.8%)
Urinary retention	8/74 (10.8%)
Urogenital disorder	6/74 (8.1%)
Reproductive system and breast disorders
Ejaculation disorder	4/74 (5.4%)
Erectile dysfunction	38/74 (51.4%)
Gynecomastia	5/74 (6.8%)
Pelvic pain	6/74 (8.1%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	5/74 (6.8%)
Cough	12/74 (16.2%)
Dyspnea	25/74 (33.8%)
Hemorrhage nasal	6/74 (8.1%)
Pharyngolaryngeal pain	4/74 (5.4%)
Respiratory disorder	4/74 (5.4%)
Skin and subcutaneous tissue disorders
Acne	6/74 (8.1%)
Alopecia	47/74 (63.5%)
Dry skin	13/74 (17.6%)
Hand-and-foot syndrome	7/74 (9.5%)
Nail disorder	20/74 (27%)
Pruritus	6/74 (8.1%)
Rash desquamating	11/74 (14.9%)
Skin disorder	10/74 (13.5%)
Sweating	5/74 (6.8%)
Vascular disorders
Flushing	4/74 (5.4%)
Hot flashes	51/74 (68.9%)
Hypertension	4/74 (5.4%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.