Radiation Therapy With or Without Antiandrogen Therapy in Treating Patients With Stage I or Stage II Prostate Cancer

• Sponsor: Radiation Therapy Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00002597
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 2,028
• Locations: 239
• Arms: 2
• Duration (Months): 283.4
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy (RT) uses high-energy x-rays to damage tumor cells. Androgens can stimulate the growth of prostate cancer cells. Hormone therapy using flutamide, goserelin, and leuprolide may fight prostate cancer by reducing the production of androgens. It is not yet known which regimen of antiandrogen therapy is most effective for prostate cancer.

PURPOSE: Randomized phase III trial to study the effectiveness of radiation therapy with or without antiandrogen therapy in treating patients who have stage I or stage II prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: flutamide; Drug: Zoladex; Drug: Lupron; Radiation: radiation therapy	Phase 3

Detailed Description

OBJECTIVES: Primary: To evaluate whether a combination of Zoladex and flutamide used as cytoreductive agents prior to and during definitive radiation therapy improves overall survival over radiation therapy alone in locally confined carcinomas of the prostate; Secondary: To compare the rates of disease-specific survival, clinical relapse (local progression and/or distant failure), freedom from prostate-specific antigen (PSA) failure, freedom from second clinical relapse, freedom from second PSA relapse, and disease-free survival; To compare the prostate re-biopsy at two years; To measure the effect on sexual function.

OUTLINE: This is a randomized, multicenter study. Patients were stratified by PSA level (less than 4 vs 4-20), tumor differentiation (well vs moderate vs poor), nodal status (N0 [nodes evaluated by surgical sampling] vs NX [nodes evaluated negative by imaging methods only]), and participating center. Patients are randomized to one of two treatment arms. Arm I: Patients receive oral flutamide 3 times a day and goserelin subcutaneously once every 4 weeks, or once as a time release injection (intramuscular leuprolide may be substituted for goserelin), beginning 2 months prior to radiotherapy and continuing until completion of radiotherapy. Patients undergo radiotherapy daily 4-5 days per week for almost 8 weeks. Arm II: Patients undergo radiotherapy only, as in arm I. Patients are followed every 3 months for the remainder of the first year, every 4 months for the second year, every 6 months for the third through fifth years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1980 patients within 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2028 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A PHASE III TRIAL OF THE STUDY OF ENDOCRINE THERAPY USED AS A CYTOREDUCTIVE AND CYTOSTATIC AGENT PRIOR TO RADIATION THERAPY IN GOOD PROGNOSIS LOCALLY CONFINED ADENOCARCINOMA OF THE PROSTATE
• Study Start Date: Oct 1, 1994
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: May 14, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Neoadjuvant TAS + RT Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.	Drug: flutamide; Two 125 mg capsules (t.i.d., p.o.) beginning two months before RT and continuing until RT is completed.; Other Names: Eulexin ; Drug: Zoladex; 3.6 mg s.c. monthly x 4 beginning two months before RT and continuing until RT is completed. The 3-month preparation may be used instead of three separate monthly injections.; Other Names: goserelin acetate ; Drug: Lupron; 7.5 mg IM (intramuscular) monthly x 4 beginning two months before RT and continuing until RT is completed. The 3-month preparation may be used instead of three separate monthly injections.; Other Names: leuprolide acetate ; Radiation: radiation therapy; 46.8 Gy (1.8 Gy/day four to five times a week [26 fx]) to regional lymphatics followed by 19.8 Gy (1.8 Gy/day x 11 fx) for a total of 66.6 Gy to the prostate. Prostate only may be treated in defined circumstances.
Other: Radiation therapy alone Radiation therapy alone	Radiation: radiation therapy; 46.8 Gy (1.8 Gy/day four to five times a week [26 fx]) to regional lymphatics followed by 19.8 Gy (1.8 Gy/day x 11 fx) for a total of 66.6 Gy to the prostate. Prostate only may be treated in defined circumstances.

Outcome Measures

Primary Outcome Measures

1. Overall Survival Rate (10-year) [From date of randomization to 10 years]

   Overall survival (OS) was calculated from randomization to the date of death from any cause and overall survival rates were estimated by the Kaplan-Meier method.

Secondary Outcome Measures

1. Disease-specific Survival Rate (10 Years) [From registration to 10 years]

   Disease-specific failure is defined as death certified as due to prostate cancer (by central review), death due to complications of treatment (irrespective of malignancy status), death from unknown causes with active malignancy, or death from unknown causes with previously documented relapse (either clinical or biochemical). Survival rates were estimated by means of cumulative incidence functions.

2. Local Progression Rate (10 Years) [From registration to 10 years]

   Local progression defined as documented local progression as determined by clinical exam . Failure rates were estimated by means of cumulative incidence functions.

3. Distant Failure Rate (10 Years) [From registration to 10 years]

   Failure is defined as documented metastatic disease. Failure rates were estimated by means of cumulative incidence functions.

4. Biochemical Failure Rate (10 Years) [From registration to 10 years]

   The Phoenix definition of biochemical failure was used - an increase in the prostate-specific antigen (PSA) level of >2 ng per milliliter above the nadir. Failure rates were estimated by means of cumulative incidence functions.

5. Clinical Relapse Rate (10 Years) [From registration to 10 years]

   Clinical relapse is defined as local progression or distant metastases. Failure rates were estimated by means of cumulative incidence functions.

6. Second Biochemical Relapse Rate (10 Years) [From registration to 10 years]

   Second biochemical relapse is as defined as follows (after initiation of salvage hormone therapy): A rise in PSA on at least two consecutive cases above the nadir (after initiation of salvage hormone therapy), with the rises in PSA exceeding 1 ng/ml above the nadir; or failure to reach 4 ng/L or less at 18 months. The rates of second biochemical relapse were estimated by means of cumulative incidence functions.

7. Disease-free Survival Rate (10 Years) [From registration to 10 years]

   Disease-free failure is defined as documentation of progression (local progression, distant failure, and biochemical failure) or death from any cause. Disease-free survival rates were estimated by the Kaplan-Meier method.

8. Positive Re-biopsy Rate at Two Years [From registration to two years]

   The rate of prostate rebiopsy at two years is defined as the proportion of patients whose results are positive among all eligible patients who had a repeat biopsy at two years. The rate was estimated separately in each arm.

Eligibility Criteria

Criteria

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

Inclusion criteria:

• Histologically confirmed locally confined adenocarcinoma of the prostate with primary tumors confined to the prostate, clinical stage T1b,1c, 2a or 2b.

• Negative nodes evaluated by imaging methods (classified in the study as NX) or by surgical sampling (classified in the study as N0).

• Karnofsky performance status ≥ 70.

• PSA is mandatory, must be ≤ 20)

• No prior hormonal therapy, radiation or chemotherapy.

• Prior finasteride for prostate hypertrophy allowed if discontinued at least 60 days prior to randomization.

• Prior testosterone administration allowed if at least 90 days elapsed since last administration.

• No evidence of distant metastasis or other synchronous primary. Patients with prior invasive malignancy who were disease free for at least 5 years could be eligible with pre-randomization approval by the study chairman.

• Treatment begins within 21 days after randomization.

• Patients signs a study-specific informed consent form.

• Alanine Aminotransferase (ALT) within 2x upper normal limits.

Exclusion criteria:

• Stage T1a or ≥ T2c disease.

• Lymph node involvement (N1 - N3).

• Evidence of distant metastasis. (M1)

• PSA > 20.

• Radical surgery or cryosurgery for carcinoma of the prostate, previous irradiation, antiandrogen therapy or chemotherapy.

• Previous or concurrent cancers other than basal cell or squamous cell skin carcinoma.

Patients with squamous cell carcinomas required to be NED (no evidence of disease) for a minimum of two years prior to study entry.

• Major medical or psychiatric illness which, in the investigator's opinion, would prevent completion of treatment and would interfere with follow-up.

• Karnofsky performance status of < 70.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama	United States	35294-3300
2	Huntsville Hospital System	Huntsville	Alabama	United States	35801-4470
3	Comprehensive Cancer Institute of Huntsville	Huntsville	Alabama	United States	35801
4	MBCCOP - Gulf Coast	Mobile	Alabama	United States	36688
5	Alabama Oncology, LLC	Montgomery	Alabama	United States	36106-2801
6	Radiation Oncology Associates of West Alabama	Tuscaloosa	Alabama	United States	35401
7	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
8	Arizona Cancer Center	Tucson	Arizona	United States	85724
9	Mount Diablo Medical Center	Concord	California	United States	94524-4110
10	Cancer Center and Beckman Research Institute, City of Hope	Duarte	California	United States	91010-3000
11	California Cancer Center	Fresno	California	United States	93720
12	Saint Agnes Cancer Center	Fresno	California	United States	93720
13	Glendale Memorial Hospital and Health Center	Glendale	California	United States	91204
14	Sutter Health Western Division Cancer Research Group	Greenbrae	California	United States	94904
15	University of California San Diego Cancer Center	La Jolla	California	United States	92093-0658
16	Loma Linda University Medical Center	Loma Linda	California	United States	92354
17	Veterans Affairs Medical Center - Long Beach	Long Beach	California	United States	90822
18	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90033-0804
19	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
20	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609-3305
21	Cancer Care Center	Pomona	California	United States	91767
22	Radiation Oncology Center - Sacramento	Sacramento	California	United States	95816
23	Radiation Medical Group, Inc.	San Diego	California	United States	92101-1492
24	UCSF Cancer Center and Cancer Research Institute	San Francisco	California	United States	94143-0128
25	O'Connor Hospital	San Jose	California	United States	95128
26	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California	United States	95403
27	Memorial Hospital Cancer Center	Colorado Springs	Colorado	United States	80909
28	University of Colorado Cancer Center	Denver	Colorado	United States	80010
29	CCOP - Christiana Care Health Services	Wilmington	Delaware	United States	19899
30	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5000
31	Lykes Center for Radiation Therapy	Clearwater	Florida	United States	33757-0210
32	Halifax Medical Center	Daytona Beach	Florida	United States	32114
33	Radiation Therapy Associates - Fort Myers	Fort Myers	Florida	United States	33901
34	University of Florida Health Science Center	Gainesville	Florida	United States	32610-0296
35	Health First Holmes Regional Medical Center	Melbourne	Florida	United States	32901
36	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
37	dVeterans Affairs Medical Center - Miami	Miami	Florida	United States	33125
38	Sylvester Cancer Center, University of Miami	Miami	Florida	United States	33136
39	Baptist Hospital of Miami	Miami	Florida	United States	33176-2197
40	Florida Radiation Oncology Group	Orange Park	Florida	United States	32073
41	MD Anderson Cancer Center Orlando	Orlando	Florida	United States	32806
42	Bay Medical Center	Panama City	Florida	United States	32401
43	Gulf Coast Cancer Treatment Center	Panama City	Florida	United States	32405-4587
44	Sarasota Radiation and Medical Oncology Center	Sarasota	Florida	United States	34233
45	Tallahassee Memorial Healthcare	Tallahassee	Florida	United States	32308
46	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612-9497
47	Emory University Hospital - Atlanta	Atlanta	Georgia	United States	30322
48	CCOP - Atlanta Regional	Atlanta	Georgia	United States	30342-1701
49	Medical Center/John B. Amos Community Cancer Center	Columbus	Georgia	United States	31902
50	InterCommunity Cancer Center at Rome	Rome	Georgia	United States	30161
51	Northwest Community Hospital	Arlington Heights	Illinois	United States	60005
52	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
53	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
54	CCOP - Central Illinois	Decatur	Illinois	United States	62526
55	Provena St. Joseph Hospital- Regional Cancer Care Center	Elgin	Illinois	United States	60123
56	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
57	Loyola University Medical Center	Maywood	Illinois	United States	60153
58	Lutheran General Cancer Care Center	Park Ridge	Illinois	United States	60068
59	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
60	St. John's Medical Center	Anderson	Indiana	United States	46016
61	Veterans Affairs Medical Center - Indianapolis (Roudebush)	Indianapolis	Indiana	United States	46202
62	Clarion Health Partners Inc.	Indianapolis	Indiana	United States	46206-1367
63	Community Hospitals of Indianapolis - Regional Cancer Center	Indianapolis	Indiana	United States	46219
64	Ball Memorial Hospital	Muncie	Indiana	United States	47303-3499
65	Wendt Regional Cancer Center of Finley Hospital	Dubuque	Iowa	United States	52001
66	Holden Comprehensive Cancer Center at The University of Iowa	Iowa City	Iowa	United States	52242-1009
67	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky	United States	40511-1093
68	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky	United States	40536-0084
69	James Graham Brown Cancer Center	Louisville	Kentucky	United States	40202
70	Louisville Radiation Oncology	Louisville	Kentucky	United States	40215
71	Merle M. Mahr Cancer Center	Madisonville	Kentucky	United States	42431
72	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	United States	70809
73	Romagosa Radiation Oncology Center	Lafayette	Louisiana	United States	70501
74	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
75	Tulane University School of Medicine	New Orleans	Louisiana	United States	70112
76	CCOP - Ochsner	New Orleans	Louisiana	United States	70121
77	Maine Medical Center	Portland	Maine	United States	04102
78	Anne Arundel Oncology Center	Annapolis	Maryland	United States	21401
79	Greater Baltimore Medical Center and Cancer Center	Baltimore	Maryland	United States	21204
80	Harbor Hospital Center	Baltimore	Maryland	United States	21225
81	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21225
82	Johns Hopkins Oncology Center	Baltimore	Maryland	United States	21231-2410
83	Radiation Oncology Affiliates of Maryland, P.A.	Baltimore	Maryland	United States	21237
84	Peninsula Regional Medical Center	Salisbury	Maryland	United States	21801
85	Cape Cod Hospital	Hyannis	Massachusetts	United States	02601
86	Veterans Affairs Medical Center - Boston (Jamaica Plain)	Jamaica Plain	Massachusetts	United States	02130
87	CCOP - Ann Arbor Regional	Ann Arbor	Michigan	United States	48106
88	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0752
89	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
90	Henry Ford Hospital	Detroit	Michigan	United States	48202
91	McLaren Regional Cancer Center	Flint	Michigan	United States	48432
92	Hurley Medical Center	Flint	Michigan	United States	48503
93	CCOP - Kalamazoo	Kalamazoo	Michigan	United States	49007-3731
94	Marquette General Hospital	Marquette	Michigan	United States	49855
95	MidMichigan Medical Center - Midland	Midland	Michigan	United States	48670
96	William Beaumont Hospital	Royal Oak	Michigan	United States	48073
97	St. Mary's Medical Center	Saginaw	Michigan	United States	48601
98	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
99	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
100	North Mississippi Medical Center/Cancer Center	Tupelo	Mississippi	United States	38801
101	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri	United States	65203
102	CCOP - Kansas City	Kansas City	Missouri	United States	64131
103	St. Louis University Health Sciences Center	Saint Louis	Missouri	United States	63110-0250
104	Mallinckrodt Institute of Radiology	Saint Louis	Missouri	United States	63110
105	Cancer Research for the Ozarks	Springfield	Missouri	United States	65807
106	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65807
107	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
108	Nebraska Health System	Omaha	Nebraska	United States	68105-1018
109	Methodist Cancer Center - Omaha	Omaha	Nebraska	United States	68114
110	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
111	Norris Cotton Cancer Center	Lebanon	New Hampshire	United States	03756-0002
112	Elliot Regional Cancer Center	Manchester	New Hampshire	United States	03103
113	Cooper Cancer Institute	Camden	New Jersey	United States	08103
114	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey	United States	07018-1095
115	John F. Kennedy Medical Center	Edison	New Jersey	United States	08818
116	Trinitas Hospital - Jersey Street Campus	Elizabeth	New Jersey	United States	07201
117	Monmouth Medical Center	Long Branch	New Jersey	United States	07740-6395
118	South Jersey Regional Cancer Center	Millville	New Jersey	United States	08332
119	Fox Chase Cancer Center at Virtua Memorial Hospital Burlington County	Mount Holly	New Jersey	United States	08060
120	Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08901
121	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
122	Atlantic City Medical Center	Pomona	New Jersey	United States	08240
123	Community Medical Center	Toms River	New Jersey	United States	08755
124	Capital Health System at Mercer	Trenton	New Jersey	United States	08607
125	St. Francis Medical Center	Trenton	New Jersey	United States	08629
126	Associated Radiologists, P.A.	Warren	New Jersey	United States	07059
127	Saint Joseph Medical Center	Albuquerque	New Mexico	United States	87102
128	Cancer Center of Albany Medical Center	Albany	New York	United States	12208
129	Albert Einstein Comprehensive Cancer Center	Bronx	New York	United States	10461
130	State University of New York Health Science Center at Brooklyn	Brooklyn	New York	United States	11203
131	New York Methodist Hospital	Brooklyn	New York	United States	11215-3609
132	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
133	Finger Lakes Radiation Oncology, P.C.	Clifton Springs	New York	United States	14432
134	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
135	Beth Israel Medical Center	New York	New York	United States	10003
136	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
137	Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
138	Champlain Valley Physicians Hospital Medical Center	Plattsburgh	New York	United States	12901
139	Vassar Brothers Hospital	Poughkeepsie	New York	United States	12601
140	University of Rochester Cancer Center	Rochester	New York	United States	14642
141	New York Medical College	Valhalla	New York	United States	10595
142	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina	United States	27599-7295
143	Northeast Medical Center	Concord	North Carolina	United States	28025
144	East Carolina University School of Medicine	Greenville	North Carolina	United States	27858-4354
145	Catawba Memorial Hospital	Hickory	North Carolina	United States	28601
146	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina	United States	27104-4241
147	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157-1082
148	Meritcare Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
149	Akron General Medical Center	Akron	Ohio	United States	44302
150	Akron City Hospital	Akron	Ohio	United States	44309
151	Christ Hospital	Cincinnati	Ohio	United States	45219
152	Ireland Cancer Center	Cleveland	Ohio	United States	44106-5065
153	University Hospitals of Cleveland	Cleveland	Ohio	United States	44106
154	CCOP - Columbus	Columbus	Ohio	United States	43206
155	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio	United States	43210-1240
156	CCOP - Dayton	Kettering	Ohio	United States	45429
157	CCOP - Toledo Community Hospital Oncology Program	Toledo	Ohio	United States	43623-3456
158	St. Anthony Hospital	Oklahoma City	Oklahoma	United States	73101
159	St. John Health System	Tulsa	Oklahoma	United States	74104
160	CCOP - Columbia River Program	Portland	Oregon	United States	97213
161	Lehigh Valley Hospital	Allentown	Pennsylvania	United States	18103
162	St. Luke's Hospital Regional Cancer Center	Bethlehem	Pennsylvania	United States	18015
163	Geisinger Medical Center	Danville	Pennsylvania	United States	17822-2001
164	Mercy Catholic Medical Center, Mercy Fitzgerald Divison	Darby	Pennsylvania	United States	19023
165	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania	United States	19026
166	Penn State Geisinger Cancer Center	Hershey	Pennsylvania	United States	17033
167	Hahnemann University Hospital	Philadelphia	Pennsylvania	United States	19102-1192
168	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania	United States	19104-4283
169	Veterans Affairs Medical Center - Philadelphia	Philadelphia	Pennsylvania	United States	19104
170	Kimmel Cancer Center of Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107-5541
171	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
172	Albert Einstein Cancer Center	Philadelphia	Pennsylvania	United States	19141
173	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15213-3489
174	Mercy Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15219
175	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania	United States	15224
176	Reading Hospital and Medical Center	Reading	Pennsylvania	United States	19612-6052
177	Mercy Hospital Cancer Center - Scranton	Scranton	Pennsylvania	United States	18501
178	Wilkes Barre General Hospital	Wilkes-Barre	Pennsylvania	United States	18764
179	CCOP - MainLine Health	Wynnewood	Pennsylvania	United States	19096
180	York Hospital	York	Pennsylvania	United States	17315
181	Roger Williams Medical Center/BUSM	Providence	Rhode Island	United States	02908-4735
182	Medical University of South Carolina	Charleston	South Carolina	United States	29425-0721
183	CCOP - Greenville	Greenville	South Carolina	United States	29615
184	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
185	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57709
186	Jackson-Madison County General Hospital	Jackson	Tennessee	United States	38301
187	University of Tennessee, Memphis Cancer Center	Memphis	Tennessee	United States	38103
188	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232-6838
189	Harrington Cancer Center	Amarillo	Texas	United States	79106
190	Julie and Ben Rogers Cancer Institute	Beaumont	Texas	United States	77701
191	University of Texas Medical Branch	Galveston	Texas	United States	77555-0209
192	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
193	Wilford Hall - 59th Medical Wing	Lackland Air Force Base	Texas	United States	78236-5300
194	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas	United States	79410-1894
195	Bayshore Medical Center	Pasadena	Texas	United States	77504
196	East Texas Medical Center - Cancer Institute	Tyler	Texas	United States	75701
197	Dixie Regional Medical Center	Saint George	Utah	United States	84770
198	University of Utah Health Sciences Center	Salt Lake City	Utah	United States	84132
199	LDS Hospital	Salt Lake City	Utah	United States	84143
200	CCOP - Southwestern Vermont Regional Cancer Center	Bennington	Vermont	United States	05201
201	Vermont Cancer Center	Burlington	Vermont	United States	05401-3498
202	Green Mountain Oncology Group	Rutland	Vermont	United States	05701
203	Martha Jefferson Hospital	Charlottesville	Virginia	United States	22901
204	Cancer Center at the University of Virginia	Charlottesville	Virginia	United States	22908
205	RMH Regional Canter Center	Harrisonburg	Virginia	United States	22801
206	Virginia Mason Medical Center	Seattle	Washington	United States	98111
207	Deaconess Medical Center	Spokane	Washington	United States	99210-0248
208	Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
209	Schiffler Cancer Center	Wheeling	West Virginia	United States	26003
210	St. Vincent Hospital	Green Bay	Wisconsin	United States	54307-3508
211	Gundersen Lutheran Medical Foundation	La Crosse	Wisconsin	United States	54601
212	Southern Wisconsin Radiotherapy Center	Madison	Wisconsin	United States	53713
213	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
214	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
215	Community Memorial Hospital	Menomonee Falls	Wisconsin	United States	53051
216	St. Joseph's Hospital	Milwaukee	Wisconsin	United States	53210
217	Columbia Hospital	Milwaukee	Wisconsin	United States	53211
218	St. Luke's Medical Center	Milwaukee	Wisconsin	United States	53215
219	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
220	Veterans Affairs Medical Center - Milwaukee (Zablocki)	Milwaukee	Wisconsin	United States	53295
221	Southeastern Wisconsin Regional Cancer Center	Racine	Wisconsin	United States	53405
222	Waukesha Memorial Hospital	Waukesha	Wisconsin	United States	53188
223	Tom Baker Cancer Center - Calgary	Calgary	Alberta	Canada	T2N 4N2
224	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
225	British Columbia Cancer Agency	Vancouver	British Columbia	Canada	V5Z 4E6
226	Saint John Regional Hospital	Saint John	New Brunswick	Canada	E2L 4L2
227	Newfoundland Cancer Treatment and Research Foundation	St. Johns	Newfoundland and Labrador	Canada	A1B 3V6
228	Nova Scotia Cancer Centre	Halifax	Nova Scotia	Canada	B3H 1V7
229	Cancer Care Ontario-Hamilton Regional Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
230	Kingston Regional Cancer Centre	Kingston	Ontario	Canada	K7L 5P9
231	Cancer Care Ontario-London Regional Cancer Centre	London	Ontario	Canada	N6A 4L6
232	Ottawa Regional Cancer Centre - General Campus	Ottawa	Ontario	Canada	K1H 1C4
233	Northeastern Ontario Regional Cancer Centre, Sudbury	Sudbury	Ontario	Canada	P3E 5J1
234	Northwestern Ontario Regional Cancer Centre, Thunder Bay	Thunder Bay	Ontario	Canada	P7A 7T1
235	Toronto Sunnybrook Regional Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
236	Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
237	CHUS-Hopital Fleurimont	Fleurimont	Quebec	Canada	J1H 5N4
238	McGill University	Montreal	Quebec	Canada	H2W 1S6
239	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4

Sponsors and Collaborators

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

Investigators

• Study Chair: David G. McGowan, MD, Cross Cancer Institute at University of Alberta

Study Documents (Full-Text)

None provided.

More Information

Publications

• Bruner D, Scott C, McGowan D, et al.: Factors influencing sexual outcomes in prostate cancer patients enrolled on radiation therapy oncology group studies 90-20 and 94-08. [Abstract] Proceedings of the International Society for Quality of Life Research 7: 575, 1998.
• Bruner DW, Scott CB, McGowan D, et al.: Validation of the sexual adjustment questionnaire (SAQ) in prostate cancer patients enrolled on Radiation Therapy Oncology Group studies 90-20 and 94-08. [Abstract] Int J Radiat Oncol Biol Phys 42 (suppl 1): A-156, 202, 1998.
• Johnke RM, Edwards JM, Evans MJ, Nangami GN, Bakken NT, Kilburn JM, Lee TK, Allison RR, Karlsson UL, Arastu HH. Circulating cytokine levels in prostate cancer patients undergoing radiation therapy: influence of neoadjuvant total androgen suppression. In Vivo. 2009 Sep-Oct;23(5):827-33.

• Responsible Party: Radiation Therapy Oncology Group
• ClinicalTrials.gov Identifier: NCT00002597
• Other Study ID Numbers: RTOG-9408; CDR0000063821
• First Posted: Feb 27, 2004
• Last Update Posted: Jun 14, 2018
• Last Verified: May 1, 2018

• Keywords provided by Radiation Therapy Oncology Group: adenocarcinoma of the prostate; stage I prostate cancer; stage IIB prostate cancer; stage IIA prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Leuprolide; Goserelin; Flutamide

Study Results

Participant Flow

Arm/Group Title	Hormone Therapy + Radiation Therapy	Radiation Therapy Alone
Arm/Group Description	Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.	Radiation therapy alone
Period Title: Overall Study
STARTED	1013	1015
COMPLETED	987	992
NOT COMPLETED	26	23

Baseline Characteristics

Arm/Group Title	Hormone Therapy + Radiation Therapy	Radiation Therapy Alone	Total
Arm/Group Description	Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.	Radiation therapy alone	Total of all reporting groups
Overall Participants	987	992	1979
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	70	71	71
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	987 100%	992 100%	1979 100%

Outcome Measures

1. Primary Outcome

Title	Overall Survival Rate (10-year)
Description	Overall survival (OS) was calculated from randomization to the date of death from any cause and overall survival rates were estimated by the Kaplan-Meier method.
Time Frame	From date of randomization to 10 years

Outcome Measure Data

Analysis Population Description

All eligible patients.

Arm/Group Title	Hormone Therapy + Radiation Therapy	Radiation Therapy Alone
Arm/Group Description	Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.	Radiation therapy alone
Measure Participants	987	992
Number (95% Confidence Interval) [percentage of patients]	61.9	56.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
	Comments	Null hypothesis: 8-year OS rate of 60% radiation therapy (RT) alone vs. 67% with hormone therapy. The study was designed with 90% power to detect a 7-percentage- point absolute difference in the 8-year survival rate, with the use of a one-sided log-rank test at the 0.025 significance level, requiring 1980 patients and 716 deaths for definitive analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0309
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; 1.01 to 1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Hormone Therapy + Radiation Therapy

2. Secondary Outcome

Title	Disease-specific Survival Rate (10 Years)
Description	Disease-specific failure is defined as death certified as due to prostate cancer (by central review), death due to complications of treatment (irrespective of malignancy status), death from unknown causes with active malignancy, or death from unknown causes with previously documented relapse (either clinical or biochemical). Survival rates were estimated by means of cumulative incidence functions.
Time Frame	From registration to 10 years

Outcome Measure Data

Analysis Population Description

All eligible patients.

Arm/Group Title	Hormone Therapy + Radiation Therapy	Radiation Therapy Alone
Arm/Group Description	Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.	Radiation therapy alone
Measure Participants	987	992
Number (95% Confidence Interval) [percentage of participants]	95.7 9.7%	92.6 9.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
	Comments	Gray's test was used to compare cumulative incidence between treatment arms (1-sided significance level of 0.025) and the Fine-Gray model was used to calculate hazard ratios.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Gray's test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.86
	Confidence Interval	(2-Sided) 95%; 1.27 to 2.74
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Hormone Therapy + Radiation Therapy

3. Secondary Outcome

Title	Local Progression Rate (10 Years)
Description	Local progression defined as documented local progression as determined by clinical exam . Failure rates were estimated by means of cumulative incidence functions.
Time Frame	From registration to 10 years

Outcome Measure Data

Analysis Population Description

All eligible patients.

Arm/Group Title	Hormone Therapy + Radiation Therapy	Radiation Therapy Alone
Arm/Group Description	Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.	Radiation therapy alone
Measure Participants	987	992
Number (95% Confidence Interval) [percentage of participants]	10.9 1.1%	16.1 1.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
	Comments	Gray's test was used to compare cumulative incidence between treatment arms (1-sided significance level of 0.025) and the Fine-Gray model was used to calculate hazard ratios.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0013
	Comments
	Method	Gray's test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; 1.17 to 1.93
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Hormone Therapy + Radiation Therapy

4. Secondary Outcome

Title	Distant Failure Rate (10 Years)
Description	Failure is defined as documented metastatic disease. Failure rates were estimated by means of cumulative incidence functions.
Time Frame	From registration to 10 years

Outcome Measure Data

Analysis Population Description

All eligible patients.

Arm/Group Title	Hormone Therapy + Radiation Therapy	Radiation Therapy Alone
Arm/Group Description	Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.	Radiation therapy alone
Measure Participants	987	992
Number (95% Confidence Interval) [percentage of participants]	5.5 0.6%	8.0 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
	Comments	Gray's test was used to compare cumulative incidence between treatment arms (1-sided significance level of 0.025) and the Fine-Gray model was used to calculate hazard ratios.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments
	Method	Gray's test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95%; 1.03 to 2.06
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Hormone Therapy + Radiation Therapy

5. Secondary Outcome

Title	Biochemical Failure Rate (10 Years)
Description	The Phoenix definition of biochemical failure was used - an increase in the prostate-specific antigen (PSA) level of >2 ng per milliliter above the nadir. Failure rates were estimated by means of cumulative incidence functions.
Time Frame	From registration to 10 years

Outcome Measure Data

Analysis Population Description

All eligible patients.

Arm/Group Title	Hormone Therapy + Radiation Therapy	Radiation Therapy Alone
Arm/Group Description	Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.	Radiation therapy alone
Measure Participants	987	992
Number (95% Confidence Interval) [percentage of participants]	26.3 2.7%	41.1 4.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
	Comments	Gray's test was used to compare cumulative incidence between treatment arms (1-sided significance level of 0.025) and the Fine-Gray model was used to calculate hazard ratios.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Gray's test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.74
	Confidence Interval	(2-Sided) 95%; 1.48 to 2.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Hormone Therapy + Radiation Therapy

6. Secondary Outcome

Title	Clinical Relapse Rate (10 Years)
Description	Clinical relapse is defined as local progression or distant metastases. Failure rates were estimated by means of cumulative incidence functions.
Time Frame	From registration to 10 years

Outcome Measure Data

Analysis Population Description

All eligible patients.

Arm/Group Title	Hormone Therapy + Radiation Therapy	Radiation Therapy Alone
Arm/Group Description	Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.	Radiation therapy alone
Measure Participants	987	992
Number (95% Confidence Interval) [percentage of participants]	15.0 1.5%	21.7 2.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
	Comments	Gray's test was used to compare cumulative incidence between treatment arms (1-sided significance level of 0.025) and the Fine-Gray model was used to calculate hazard ratios.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Gray's test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; 1.21 to 1.85
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Hormone Therapy + Radiation Therapy

7. Secondary Outcome

Title	Second Biochemical Relapse Rate (10 Years)
Description	Second biochemical relapse is as defined as follows (after initiation of salvage hormone therapy): A rise in PSA on at least two consecutive cases above the nadir (after initiation of salvage hormone therapy), with the rises in PSA exceeding 1 ng/ml above the nadir; or failure to reach 4 ng/L or less at 18 months. The rates of second biochemical relapse were estimated by means of cumulative incidence functions.
Time Frame	From registration to 10 years

Outcome Measure Data

Analysis Population Description

All eligible patients.

Arm/Group Title	Hormone Therapy + Radiation Therapy	Radiation Therapy Alone
Arm/Group Description	Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.	Radiation therapy alone
Measure Participants	987	992
Number (95% Confidence Interval) [percentage of participants]	2.7 0.3%	6.1 0.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
	Comments	Gray's test was used to compare cumulative incidence between treatment arms (1-sided significance level of 0.025) and the Fine-Gray model was used to calculate hazard ratios.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Gray's test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.06
	Confidence Interval	(2-Sided) 95%; 1.34 to 3.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Hormone Therapy + Radiation Therapy

8. Secondary Outcome

Title	Disease-free Survival Rate (10 Years)
Description	Disease-free failure is defined as documentation of progression (local progression, distant failure, and biochemical failure) or death from any cause. Disease-free survival rates were estimated by the Kaplan-Meier method.
Time Frame	From registration to 10 years

Outcome Measure Data

Analysis Population Description

All eligible patients.

Arm/Group Title	Hormone Therapy + Radiation Therapy	Radiation Therapy Alone
Arm/Group Description	Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.	Radiation therapy alone
Measure Participants	987	992
Number (95% Confidence Interval) [percentage of participants]	51.7 5.2%	39.5 4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
	Comments	Treatment arms were compared using the log-rank test (one-sided significance level of 0.025).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.38
	Confidence Interval	(2-Sided) 95%; 1.22 to 1.56
	Parameter Dispersion	Type: Value:
	Estimation Comments	Reference level = Hormone Therapy + Radiation Therapy

9. Secondary Outcome

Title	Positive Re-biopsy Rate at Two Years
Description	The rate of prostate rebiopsy at two years is defined as the proportion of patients whose results are positive among all eligible patients who had a repeat biopsy at two years. The rate was estimated separately in each arm.
Time Frame	From registration to two years

Outcome Measure Data

Analysis Population Description

All eligible patients who had a repeat biopsy at 2 years.

Arm/Group Title	Hormone Therapy + Radiation Therapy	Radiation Therapy Alone
Arm/Group Description	Neoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.	Radiation therapy alone
Measure Participants	439	404
Number [percentage of participants]	20.2 2%	38.9 3.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hormone Therapy + Radiation Therapy, Radiation Therapy Alone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Adverse Event Reporting Description	Eligible patients who received treatment. Subjects experiencing more than one of a given adverse event are counted only once for that adverse event.
Arm/Group Title	Neoadjuvant TAS 2 Months Before and During RT		Radiation Therapy Alone
Arm/Group Description	Neoadjuvant Total Androgen Suppression (TAS) two months before and during radiation therapy		Radiation therapy alone
All Cause Mortality
	Neoadjuvant TAS 2 Months Before and During RT		Radiation Therapy Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Neoadjuvant TAS 2 Months Before and During RT		Radiation Therapy Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/1003 (3.3%)		16/1003 (1.6%)
Blood and lymphatic system disorders
Acute RT Toxicity: Hematologic: NOS	7/1003 (0.7%)		5/1003 (0.5%)
Hormone Toxicity: Hematologic : NOS	1/1003 (0.1%)		0/1003 (0%)
Late RT Toxicity: Hematologic: NOS	8/1003 (0.8%)		3/1003 (0.3%)
Gastrointestinal disorders
Acute RT Toxicity: Bowel: NOS	1/1003 (0.1%)		0/1003 (0%)
Late RT Toxicity: Bowel: NOS	1/1003 (0.1%)		3/1003 (0.3%)
Late RT Toxicity: Other GI: NOS	2/1003 (0.2%)		0/1003 (0%)
General disorders
Late RT Toxicity: Other: NOS	3/1003 (0.3%)		0/1003 (0%)
Hepatobiliary disorders
Hormone Toxicity: Liver : NOS	3/1003 (0.3%)		0/1003 (0%)
Renal and urinary disorders
Acute RT Toxicity: Bladder: NOS	4/1003 (0.4%)		4/1003 (0.4%)
Late RT Toxicity: Bladder: NOS	12/1003 (1.2%)		0/1003 (0%)
Late RT Toxicity: Other GU: NOS	0/1003 (0%)		1/1003 (0.1%)
Other (Not Including Serious) Adverse Events
	Neoadjuvant TAS 2 Months Before and During RT		Radiation Therapy Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	975/1003 (97.2%)		955/1003 (95.2%)
Blood and lymphatic system disorders
Acute RT Toxicity: Hematologic: NOS	127/1003 (12.7%)		67/1003 (6.7%)
Hormone Toxicity: Hematologic : NOS	172/1003 (17.1%)		0/1003 (0%)
Late RT Toxicity: Hematologic: NOS	135/1003 (13.5%)		109/1003 (10.9%)
Gastrointestinal disorders
Acute RT Toxicity: Bowel: NOS	439/1003 (43.8%)		501/1003 (50%)
Late RT Toxicity: Bowel: NOS	262/1003 (26.1%)		210/1003 (20.9%)
General disorders
Acute RT Toxicity: Other: NOS	135/1003 (13.5%)		138/1003 (13.8%)
Late RT Toxicity: Other: NOS	84/1003 (8.4%)		99/1003 (9.9%)
Hepatobiliary disorders
Hormone Toxicity: Liver : NOS	93/1003 (9.3%)		0/1003 (0%)
Renal and urinary disorders
Acute RT Toxicity: Bladder: NOS	149/1003 (14.9%)		190/1003 (18.9%)
Late RT Toxicity: Bladder: NOS	182/1003 (18.1%)		166/1003 (16.6%)
Reproductive system and breast disorders
Hormone Toxicity: Impotence : NOS	238/1003 (23.7%)		0/1003 (0%)
Late RT Toxicity: Other GU: NOS	69/1003 (6.9%)		78/1003 (7.8%)
Vascular disorders
Hormone Toxicity: Hot flashes : NOS	295/1003 (29.4%)		0/1003 (0%)

Limitations/Caveats

[Not Specified]

More Information

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.