Sulfasalazine in Preventing Acute Diarrhea in Patients With Cancer Who Are Undergoing Pelvic Radiation Therapy

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT01198145
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 87
• Locations: 257
• Arms: 2
• Actual Duration (Months): 75.5
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Sulfasalazine may relieve diarrhea in patients with cancer who are undergoing pelvic radiation therapy.

PURPOSE: This randomized phase III trial is studying sulfasalazine to see how well it works in preventing acute diarrhea in patients with cancer who are undergoing pelvic radiation therapy.

Condition or Disease	Intervention/Treatment	Phase
Diarrhea; Gastrointestinal Complications; Unspecified Adult Solid Tumor, Protocol Specific	Drug: sulfasalazine; Other: placebo	Phase 3

Detailed Description

OBJECTIVES:

Primary

• To determine whether sulfasalazine is effective in reducing the acute treatment-related diarrhea in patients receiving pelvic radiotherapy as measured by NCI CTC v4.0 in patients receiving pelvic external-beam radiotherapy as adjuvant or primary treatment for malignancy.

Secondary

• To determine whether sulfasalazine can reduce chronic treatment-related bowel dysfunction following completion of therapy.

• To determine whether sulfasalazine causes any toxicity in this situation.

Tertiary

• To bank blood products for future studies, as part of ongoing research for NCCTG studies (Mayo Clinic Rochester only). (Translational)

OUTLINE: This is a multicenter study. Patients are stratified according to history of anterior resection of the rectum (yes vs no); total planned cumulative dosing, including boost fields of external-beam radiotherapy (4500-5350 cGy vs > 5350 cGy); and concurrent radiosensitizing fluorouracil, capecitabine, or oxaliplatin (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral sulfasalazine twice daily during radiotherapy* and for 4 weeks after completion of radiotherapy.

• Arm II: Patients receive oral placebo twice daily during radiotherapy* and for 4 weeks after completion of radiotherapy.

NOTE: *Patients must start study treatment by the third radiotherapy fraction.

Patients may undergo blood sample collection at baseline and then weekly during radiotherapy. All patients complete quality of life and bowel function questionnaires at baseline, weekly during radiotherapy, and at 6 weeks after completion of radiotherapy.

After completion of radiotherapy, patients are followed up at 6 weeks and at 12 and 24 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 87 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Phase III, Randomized, Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy
• Actual Study Start Date: Apr 1, 2011
• Actual Primary Completion Date: Jul 22, 2013
• Actual Study Completion Date: Jul 15, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I: Sulfasalazine Patients receive oral sulfasalazine twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.	Drug: sulfasalazine; Given orally
Placebo Comparator: Arm II: Placebo Patients receive oral placebo twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.	Other: placebo; Given orally

Outcome Measures

Primary Outcome Measures

1. Maximum Severity of Diarrhea Toxicity as Measured by the CTCAE v4.0 During and After Radiotherapy (RT) [During radiation therapy and up to 6 weeks post radiation therapy]

   The primary endpoint for this study is the maximal severity of diarrhea toxicity. Severity of diarrhea was graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grade 0 = None; 1=Mild; Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening as measured by the CTCAE version 4.0. Assessments were recorded during the course of RT and for 6 weeks following RT. The table below represents the worst graded diarrhea for each patient. A two-sided Wilcoxon rank-sum test will be used to test the equality of the distributions of maximum diarrhea severity grades between the two treatment arms.

Secondary Outcome Measures

1. Maximum Severity of Each Outcome Variable (Rectal Bleeding, Abdominal Cramping, Tenesmus, Constipation, and Diarrhea) Measured During and After RT [During radiation therapy and up to 6 weeks post radiation therapy]

   The maximal severity of each of 5 different adverse even types (Tenesmus, Abdominal Pain, Constipation, Diarrhea, and Rectal Bleeding) were collected as a secondary endpoint. Severity of the events was graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grade 0 = None; 1=Mild; Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening. Adverse events were assessed during the course of RT and for 6 weeks following RT. The table below represents the worst grade for each patient for each type. Two-sided chi-square tests will be used to compare each percentage variable between treatment arms for each event type.

2. Area Under the Curve That Combines the Individual Severity of Diarrhea Toxicity as Measured by the CTCAE v4.0 During and After RT [During radiation therapy and up to 6 weeks post radiation therapy]

   For each patient, an Area Under the Curve (AUC) summary statistic will be calculated taking into account the individual severity of diarrhea toxicity over time. Severity of diarrhea was graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grade 0 = None; 1=Mild; Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening. The curve was constructed using weekly assessments during and after RT. A separate analysis was done during the course of RT and every week for 6 weeks following RT.

3. Average Graded Severity for Tenesmus, Abdominal Pain, Constipation, Diarrhea and Hemorrhage During and After RT as Graded by CTCAE v4.0 [During radiation therapy and up to 6 weeks post radiation therapy]

   Tenesmus, Abdominal pain, constipation, diarrhea and hemorrhaging were assessed during RT and up to 6 weeks after RT. Severity of these events were graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grade 0 = None; 1=Mild; Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening. For each patient, an average score for each outcome variable during and after RT calculated as follows: The sum of all severity scores for that variable divided by the number of severity scores for that variable recorded for the patient during the course of RT and for 6 weeks following RT.

4. Percentage of Patients in Each Arm That Experience Tenesmus, Abdominal Pain, Constipation, Diarrhea and Rectal Bleeding During and After RT [During radiation therapy and up to 6 weeks post radiation therapy]

   The number of patients that reported any grade 1 or higher adverse event was divided by the total number of patients evaluated. The analysis was done separately for each of the 5 outcomes and separately during RT and after RT.

5. Percent of Patients in Each Arm That Recorded "Yes" to Each of Questions 2-10 on the Bowel Function Questionnaire [Up to 6 weeks post radiation therapy]

   Questions that were used in this analysis: 2. Have you had a problem causing you to get up at night to have a bowel movement? 3. Have you had a problem causing you to lose control of your bowel movements? 4. Have you had a problem causing you to have a bowel movement within 30 minutes of a prior bowel movement? 5. Have you had to wear protective clothing or a pad in case you lost control of a bowel movement? 6. Have you had a problem causing you to be unable to tell the difference between stool and gas? 7. Have you had a problem causing you to have stools that are liquid? 1=yes 2=no q08 8. Have you found that once you feel the urge to have a bowel movement, you must do so within 15 minutes to avoid an accident? 9. Have you had cramping with a bowel movement? 10. Have you had blood in your bowel movement?

6. Percentage of Patients in Each Arm That Require Any Type of Antidiarrheal Medications. [Up to 24 months post radiotherapy]

   The number of patients reporting the use of anti-diarrheal medications divided by the number of patients evaluated for this endpoint.

7. Percentage of Patients in Each Arm That Experience Clinically Significant Deficits in Overall Quality of Life and Fatigue [Up to 6 weeks post radiotherapy]

   For each arm, the percentage of patients experience clinically significant deficits in overall QOL and fatigue as indicated by a score of 5 or lower on the 0-10 scale. The analysis was done using the questionnaire that was completed during the first week of radiotherapy (RT) and 6 weeks after RT.

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Diagnosis of cancer that supports the use of radiotherapy to the pelvis

• No current or prior metastases beyond pelvic regional lymph nodes

• Planning to receive a course of continuous definitive or adjuvant external-beam radiotherapy to a minimum dose of 4500 cGy with or without fluorouracil, capecitabine, or oxaliplatin

• Planned course of pelvic radiotherapy must fall within the following parameters:

• Pelvis must be encompassed by the planned radiotherapy fields

• Superior border may not lie superior to the L4-5 interspace and may not be inferior to the most inferior aspect of the sacroiliac joints

• Portions of the rectum may have special blocking, depending upon disease site

• Total planned dose to the central axis midplane (for AP-PA parallel opposed fields) or isocenter (for 3- or 4-field techniques) for the pelvic field must lie between 4500-5300 cGy (inclusive)*

• Subsequent to completion of treatment to the pelvic field, a boost to primary tumor or tumor bed may be planned

• Planned treatment is to be given 4-5 times per week on a one-treatment-per-day basis

• Daily dose (specified at central axis midplane or at isocenter for multi-field techniques) must lie between 170-210 cGy (inclusive) per day*

• NOTE: *For institutions that do not use midplane or isocenter as the point for specification of dose, it will be necessary to determine the dose according to the methods specified above in order to determine patient eligibility.

• No perineal irradiation planned (e.g., anal cancer patients, patients who have had an abdominal-perineal resection)

• No brachytherapy planned before the completion of all external-beam radiotherapy

• No planned split-course radiotherapy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2

• Life expectancy ≥ 6 months

• Hemoglobin ≥ 10.0 g/dL

• Leukocytes ≥ 3,500/mm^3

• ANC ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

• AST ≤ 1.5 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Willing to provide blood specimens as required by the study (Mayo Clinic Rochester patients only)

• Able to complete questionnaires alone or with assistance

• No history of inflammatory bowel disease

• No history of gastrointestinal or genitourinary obstruction or porphyria

• No history of G6PD deficiency

• No history of irritable bowel syndrome

• No history of blood dyscrasia

• No history of severe allergies or asthma

• No history of hepatic or renal disease

• No diarrhea ≥ grade 3, rectal bleeding, abdominal cramping, or incontinence of stool within the past week

• No medical condition that may interfere with the ability to receive study treatment

• No known allergy to sulfasalazine, sulfa medications, salicylates, or any known component of drug formulation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior pelvic radiotherapy

• No prior abdominal-perineal resection, Hartmann procedure, or other surgical procedure leaving the patient without a functioning rectum

• No planned use of leucovorin or cytotoxic chemotherapeutic agents concurrent with radiotherapy (except for fluorouracil, capecitabine, or oxaliplatin)

• No other concurrent sulfasalazine

• No concurrent digoxin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Hospital	Phoenix	Arizona	United States	85054
2	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
3	Aurora Presbyterian Hospital	Aurora	Colorado	United States	80012
4	Boulder Community Hospital	Boulder	Colorado	United States	80301-9019
5	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado	United States	80933
6	St. Anthony Central Hospital	Denver	Colorado	United States	80204
7	Porter Adventist Hospital	Denver	Colorado	United States	80210
8	Presbyterian - St. Luke's Medical Center	Denver	Colorado	United States	80218
9	St. Joseph Hospital	Denver	Colorado	United States	80218
10	Rose Medical Center	Denver	Colorado	United States	80220
11	Swedish Medical Center	Englewood	Colorado	United States	80110
12	North Colorado Medical Center	Greeley	Colorado	United States	80631
13	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
14	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado	United States	80501
15	McKee Medical Center	Loveland	Colorado	United States	80539
16	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado	United States	81004
17	North Suburban Medical Center	Thornton	Colorado	United States	80229
18	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
19	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
20	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware	United States	19958
21	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
22	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia	United States	30912
23	Kapiolani Medical Center at Pali Momi	'Aiea	Hawaii	United States	96701
24	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	96813
25	OnCare Hawaii, Incorporated - Lusitana	Honolulu	Hawaii	United States	96813
26	Queen's Cancer Institute at Queen's Medical Center	Honolulu	Hawaii	United States	96813
27	Straub Clinic and Hospital, Incorporated	Honolulu	Hawaii	United States	96813
28	Hawaii Medical Center - East	Honolulu	Hawaii	United States	96817
29	OnCare Hawaii, Incorporated - Kuakini	Honolulu	Hawaii	United States	96817
30	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
31	Tripler Army Medical Center	Honolulu	Hawaii	United States	96859
32	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
33	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60504
34	Louis A. Weiss Memorial Hospital	Chicago	Illinois	United States	60640
35	Ingalls Cancer Care Center at Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
36	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois	United States	61265
37		Moline	Illinois	United States	61265
38	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
39	Elkhart Clinic, LLC	Elkhart	Indiana	United States	46514-2098
40	Michiana Hematology-Oncology, PC - Elkhart	Elkhart	Indiana	United States	46514
41	Elkhart General Hospital	Elkhart	Indiana	United States	46515
42	St. Francis Hospital Cancer Care Services	Indianapolis	Indiana	United States	46237
43	Howard Community Hospital	Kokomo	Indiana	United States	46904
44	Michiana Hematology-Oncology, PC - South Bend	Mishawaka	Indiana	United States	46545-1470
45	Saint Joseph Regional Medical Center	Mishawaka	Indiana	United States	46545-1470
46	Michiana Hematology Oncology PC - Plymouth	Plymouth	Indiana	United States	46563
47	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
48	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
49	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
50	Michiana Hematology Oncology PC - La Porte	Westville	Indiana	United States	46391
51		Bettendorf	Iowa	United States	52722
52	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
53	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
54	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa	United States	50325
55	Mercy Cancer Center - West Lakes	Clive	Iowa	United States	50325
56	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
57	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
58	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
59	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
60	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
61	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
62	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
63	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51102
64	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
65	Methodist West Hospital	West Des Moines	Iowa	United States	50266-7700
66	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
67	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
68	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
69	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
70	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
71	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
72	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
73	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas	United States	67901
74	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
75	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
76	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
77	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
78	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
79	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
80	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
81	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
82	CCOP - Wichita	Wichita	Kansas	United States	67214
83	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
84	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
85	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
86	Union Hospital of Cecil County	Elkton	Maryland	United States	21921
87	Boston University Cancer Research Center	Boston	Massachusetts	United States	02118
88	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
89	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
90	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
91	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
92	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
93	Hurley Medical Center	Flint	Michigan	United States	48503
94	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
95	Foote Memorial Hospital	Jackson	Michigan	United States	49201
96	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
97	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
98	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
99	Mercy Memorial Hospital - Monroe	Monroe	Michigan	United States	48162
100	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
101	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
102	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
103	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan	United States	49085
104	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan	United States	49085
105	St. John Macomb Hospital	Warren	Michigan	United States	48093
106	MeritCare Bemidji	Bemidji	Minnesota	United States	56601
107	St. Joseph's Medical Center	Brainerd	Minnesota	United States	56401
108	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
109	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
110	Essentia Health - Duluth Clinic	Duluth	Minnesota	United States	55805-1983
111	CCOP - Duluth	Duluth	Minnesota	United States	55805
112	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
113	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
114	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
115	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
116	Immanuel St. Joseph's	Mankato	Minnesota	United States	56002
117	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
118	Minnesota Oncology - Maplewood	Maplewood	Minnesota	United States	55109
119	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
120	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
121	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
122	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
123	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
124	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
125	Regions Hospital Cancer Care Center	Saint Paul	Minnesota	United States	55101
126	United Hospital	Saint Paul	Minnesota	United States	55102
127	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
128	Lakeview Hospital	Stillwater	Minnesota	United States	55082
129	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
130	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota	United States	56201
131	Minnesota Oncology - Woodbury	Woodbury	Minnesota	United States	55125
132	Central Care Cancer Center at Carrie J. Babb Cancer Center	Bolivar	Missouri	United States	65613
133	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
134	Goldschmidt Cancer Center	Jefferson City	Missouri	United States	65109
135	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
136	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65804
137	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
138	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
139	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
140	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59102
141	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
142	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
143	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
144	Benefis Sletten Cancer Institute	Great Falls	Montana	United States	59405
145	St. Peter's Hospital	Helena	Montana	United States	59601
146	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
147	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
148	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
149	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
150	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
151	Immanuel Medical Center	Omaha	Nebraska	United States	68122
152	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
153	Lakeside Hospital	Omaha	Nebraska	United States	68130
154	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
155	New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care	Concord	New Hampshire	United States	03301
156	New Hampshire Oncology - Hematology, PA - Hooksett	Hooksett	New Hampshire	United States	03106
157	Lakes Region General Hospital	Laconia	New Hampshire	United States	03246
158	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
159	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
160	University of New Mexico Cancer Center - South	Las Cruces	New Mexico	United States	88011
161	Mount Kisco Medical Group, PC	Mount Kisco	New York	United States	10549-3417
162	Randolph Hospital	Asheboro	North Carolina	United States	27203-5400
163	CaroMont Cancer Center at Gaston Memorial Hospital	Gastonia	North Carolina	United States	28053
164	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
165	Moses Cone Regional Cancer Center at Wesley Long Community Hospital	Greensboro	North Carolina	United States	27403-1198
166	Park Ridge Hospital	Hendersonville	North Carolina	United States	28792
167	High Point Regional Hospital	High Point	North Carolina	United States	27261
168	Annie Penn Cancer Center	Reidsville	North Carolina	United States	27320
169	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
170	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
171	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
172	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
173	MeritCare Broadway	Fargo	North Dakota	United States	58102
174	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota	United States	58201
175	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
176	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
177	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210-1240
178	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
179	CCOP - Columbus	Columbus	Ohio	United States	43215
180	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
181	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
182	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
183	Grandview Hospital	Dayton	Ohio	United States	45405
184	Good Samaritan Hospital	Dayton	Ohio	United States	45406
185	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
186	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
187	CCOP - Dayton	Dayton	Ohio	United States	45420
188	Grady Memorial Hospital	Delaware	Ohio	United States	43015
189	Community Cancer Center	Elyria	Ohio	United States	44035
190	Hematology Oncology Center	Elyria	Ohio	United States	44035
191	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
192	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
193	Wayne Hospital	Greenville	Ohio	United States	45331
194	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
195	Fairfield Medical Center	Lancaster	Ohio	United States	43130
196	Lima Memorial Hospital	Lima	Ohio	United States	45804
197	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
198	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537-1839
199	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
200	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
201	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
202	Toledo Clinic - Oregon	Oregon	Ohio	United States	43616
203	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
204	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
205	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
206	Toledo Hospital	Toledo	Ohio	United States	43606
207	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
208	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
209	St. Anne Mercy Hospital	Toledo	Ohio	United States	43623
210	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
211	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
212	Fulton County Health Center	Wauseon	Ohio	United States	43567
213	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
214	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
215	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
216	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma	United States	74136
217	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
218	Legacy Good Samaritan Hospital & Comprehensive Cancer Center	Portland	Oregon	United States	97210
219	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
220	AnMed Cancer Center	Anderson	South Carolina	United States	29621
221	Bon Secours St. Francis Health System	Greenville	South Carolina	United States	29601
222	Cancer Centers of the Carolinas - Faris Road	Greenville	South Carolina	United States	29605
223	Greenville Hospital Cancer Center	Greenville	South Carolina	United States	29605
224	CCOP - Greenville	Greenville	South Carolina	United States	29615
225	Cancer Centers of the Carolinas - Seneca	Seneca	South Carolina	United States	29672
226	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
227	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
228	Cancer Centers of the Carolinas - Spartanburg	Spartanburg	South Carolina	United States	29307
229	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
230	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
231	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
232	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee	United States	37662
233	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
234	Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County	Martinsville	Virginia	United States	24115
235	Legacy Salmon Creek Medical Center	Vancouver	Washington	United States	98686
236	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia	United States	25701
237	Center for Cancer Treatment & Prevention at Sacred Heart Hospital	Eau Claire	Wisconsin	United States	54701
238	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin	United States	54701
239	Central Wisconsin Cancer Program at Agnesian HealthCare	Fond Du Lac	Wisconsin	United States	54935
240	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
241	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
242	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
243	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
244	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin	United States	54601
245	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin	United States	54221-1450
246	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
247	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
248	Saint Joseph's Hospital	Marshfield	Wisconsin	United States	54449
249	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin	United States	54548
250	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
251	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin	United States	54868
252	St. Nicholas Hospital	Sheboygan	Wisconsin	United States	53081
253	Marshfield Clinic at Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
254	Saint Michael's Hospital Cancer Center	Stevens Point	Wisconsin	United States	54481
255	Door County Cancer Center at Door County Memorial Hospital	Sturgeon Bay	Wisconsin	United States	54235-1495
256	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
257	Ministry Saint Clare's Hospital	Weston	Wisconsin	United States	54476

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Robert C. Miller, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT01198145
• Other Study ID Numbers: NCCTG-N08C9; NCI-2011-02602; CDR0000684240
• First Posted: Sep 9, 2010
• Last Update Posted: May 12, 2020
• Last Verified: Apr 1, 2020

• Keywords provided by Alliance for Clinical Trials in Oncology: diarrhea; gastrointestinal complications; unspecified adult solid tumor, protocol specific
• Additional relevant MeSH terms: Diarrhea; Sulfasalazine

Study Results

Participant Flow

Arm/Group Title	Arm I: Sulfasalazine	Arm II: Placebo
Arm/Group Description	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy. > > placebo: Given orally
Period Title: Overall Study
STARTED	44	43
COMPLETED	43	42
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Arm I: Sulfasalazine	Arm II: Placebo	Total
Arm/Group Description	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.> > placebo: Given orally	Total of all reporting groups
Overall Participants	42	42	84
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59	56.5	58
Sex: Female, Male (Count of Participants)
Female	15 35.7%	18 42.9%	33 39.3%
Male	27 64.3%	24 57.1%	51 60.7%
Region of Enrollment (participants) [Number]
United States	42 100%	42 100%	84 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Severity of Diarrhea Toxicity as Measured by the CTCAE v4.0 During and After Radiotherapy (RT)
Description	The primary endpoint for this study is the maximal severity of diarrhea toxicity. Severity of diarrhea was graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grade 0 = None; 1=Mild; Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening as measured by the CTCAE version 4.0. Assessments were recorded during the course of RT and for 6 weeks following RT. The table below represents the worst graded diarrhea for each patient. A two-sided Wilcoxon rank-sum test will be used to test the equality of the distributions of maximum diarrhea severity grades between the two treatment arms.
Time Frame	During radiation therapy and up to 6 weeks post radiation therapy

Outcome Measure Data

Analysis Population Description

Two patients in Arm I and one patient from Arm II were not included in the baseline analysis nor the endpoint analyses due to cancellations and protocol violations.

Arm/Group Title	Arm I: Sulfasalazine	Arm II: Placebo
Arm/Group Description	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy. > > placebo: Given orally
Measure Participants	42	42
Grade 0	10 23.8%	10 23.8%
Grade 1	13 31%	15 35.7%
Grade 2	8 19%	13 31%
Grade 3	10 23.8%	4 9.5%
Grade 4	1 2.4%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I: Sulfasalazine, Arm II: Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.41
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Maximum Severity of Each Outcome Variable (Rectal Bleeding, Abdominal Cramping, Tenesmus, Constipation, and Diarrhea) Measured During and After RT
Description	The maximal severity of each of 5 different adverse even types (Tenesmus, Abdominal Pain, Constipation, Diarrhea, and Rectal Bleeding) were collected as a secondary endpoint. Severity of the events was graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grade 0 = None; 1=Mild; Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening. Adverse events were assessed during the course of RT and for 6 weeks following RT. The table below represents the worst grade for each patient for each type. Two-sided chi-square tests will be used to compare each percentage variable between treatment arms for each event type.
Time Frame	During radiation therapy and up to 6 weeks post radiation therapy

Outcome Measure Data

Analysis Population Description

Two patients in Arm I and one patient from Arm II were not included in the endpoint analyses due to cancellations and protocol violations. 42 patients from each arm started RT and were used for the analysis. 25 patients from Arm I and 29 patients from Arm II were evaluated after RT. Two patients from Arm 1 provided incomplete data.

Arm/Group Title	Arm I: Sulfasalazine	Arm II: Placebo
Arm/Group Description	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
Measure Participants	42	42
Grade 0	27 64.3%	30 71.4%
Grade 1	6 14.3%	9 21.4%
Grade 2	7 16.7%	3 7.1%
Grade 3	2 4.8%	0 0%
Grade 4	0 0%	0 0%
Grade 0	18 42.9%	21 50%
Grade 1	5 11.9%	7 16.7%
Grade 2	0 0%	1 2.4%
Grade 3	0 0%	0 0%
Grade 4	0 0%	0 0%
Grade 0	22 52.4%	26 61.9%
Grade 1	14 33.3%	12 28.6%
Grade 2	3 7.1%	4 9.5%
Grade 3	3 7.1%	0 0%
Grade 4	0 0%	0 0%
Grade 0	17 40.5%	24 57.1%
Grade 1	8 19%	2 4.8%
Grade 2	0 0%	3 7.1%
Grade 3	0 0%	0 0%
Grade 4	0 0%	0 0%
Grade 0	26 61.9%	27 64.3%
Grade 1	12 28.6%	13 31%
Grade 2	4 9.5%	2 4.8%
Grade 3	0 0%	0 0%
Grade 4	0 0%	0 0%
Grade 0	19 45.2%	22 52.4%
Grade 1	6 14.3%	6 14.3%
Grade 2	0 0%	1 2.4%
Grade 3	0 0%	0 0%
Grade 4	0 0%	0 0%
Grade 0	10 23.8%	11 26.2%
Grade 1	13 31%	14 33.3%
Grade 2	9 21.4%	13 31%
Grade 3	9 21.4%	4 9.5%
Grade 4	1 2.4%	0 0%
Grade 0	11 26.2%	14 33.3%
Grade 1	12 28.6%	10 23.8%
Grade 2	2 4.8%	3 7.1%
Grade 3	0 0%	2 4.8%
Grade 4	0 0%	0 0%
Grade 0	26 61.9%	22 52.4%
Grade 1	16 38.1%	20 47.6%
Grade 2	0 0%	0 0%
Grade 3	0 0%	0 0%
Grade 4	0 0%	0 0%
Grade 0	20 47.6%	27 64.3%
Grade 1	5 11.9%	2 4.8%
Grade 2	0 0%	0 0%
Grade 3	0 0%	0 0%
Grade 4	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I: Sulfasalazine, Arm II: Placebo
	Comments	Comparing Tenesmus During RT
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I: Sulfasalazine, Arm II: Placebo
	Comments	Comparing Tenesmus after RT
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.64
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm I: Sulfasalazine, Arm II: Placebo
	Comments	Comparing abdominal pain during RT.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm I: Sulfasalazine, Arm II: Placebo
	Comments	Comparing abdominal pain after RT
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Arm I: Sulfasalazine, Arm II: Placebo
	Comments	Comparing constipation during RT
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Arm I: Sulfasalazine, Arm II: Placebo
	Comments	Comparing constipation after RT
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.63
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Arm I: Sulfasalazine, Arm II: Placebo
	Comments	Comparing diarrhea during RT
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Arm I: Sulfasalazine, Arm II: Placebo
	Comments	Comparing diarrhea after RT
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Arm I: Sulfasalazine, Arm II: Placebo
	Comments	Comparing rectal bleeding during RT
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments
	Method	Chi-squared
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Arm I: Sulfasalazine, Arm II: Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Area Under the Curve That Combines the Individual Severity of Diarrhea Toxicity as Measured by the CTCAE v4.0 During and After RT
Description	For each patient, an Area Under the Curve (AUC) summary statistic will be calculated taking into account the individual severity of diarrhea toxicity over time. Severity of diarrhea was graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grade 0 = None; 1=Mild; Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening. The curve was constructed using weekly assessments during and after RT. A separate analysis was done during the course of RT and every week for 6 weeks following RT.
Time Frame	During radiation therapy and up to 6 weeks post radiation therapy

Outcome Measure Data

Analysis Population Description

Two patients in Arm I and one patient from Arm II were not included in the endpoint analyses due to cancellations and protocol violations. 42 patients from each arm started RT and were used in that portion of the analysis. 25 patients from Arm I and 29 patients from Arm II were evaluated after RT. Two patients from Arm 1 provided incomplete data.

Arm/Group Title	Arm I: Sulfasalazine	Arm II: Placebo
Arm/Group Description	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
Measure Participants	42	42
During RT	4.0 (3.9)	3.3 (3.0)
After RT	1.2 (1.7)	1.3 (2.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I: Sulfasalazine, Arm II: Placebo
	Comments	Result comparing Arm I and Arm II during RT.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.56
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm I: Sulfasalazine, Arm II: Placebo
	Comments	Result comparing Arm I and Arm II after RT.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.74
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Average Graded Severity for Tenesmus, Abdominal Pain, Constipation, Diarrhea and Hemorrhage During and After RT as Graded by CTCAE v4.0
Description	Tenesmus, Abdominal pain, constipation, diarrhea and hemorrhaging were assessed during RT and up to 6 weeks after RT. Severity of these events were graded using the terminology and grading categories defined in the NCI's Common Toxicity Criteria (CTCAE), Version 4.0. Grade 0 = None; 1=Mild; Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening. For each patient, an average score for each outcome variable during and after RT calculated as follows: The sum of all severity scores for that variable divided by the number of severity scores for that variable recorded for the patient during the course of RT and for 6 weeks following RT.
Time Frame	During radiation therapy and up to 6 weeks post radiation therapy

Outcome Measure Data

Analysis Population Description

Two patients in Arm I and one patient from Arm II were not included in the endpoint analyses due to cancellations and protocol violations. 42 patients from each arm started RT and were used in that portion of the analysis. 25 patients from Arm I and 29 patients from Arm II were evaluated after RT. Two patients from Arm 1 provided incomplete data.

Arm/Group Title	Arm I: Sulfasalazine	Arm II: Placebo
Arm/Group Description	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
Measure Participants	42	42
Tenesmus during RT	0.2 (0.4)	0.1 (0.2)
Tenesmus after RT	0.1 (0.2)	0.1 (0.4)
Abdominal pain during RT	0.3 (0.4)	0.2 (0.3)
Abdominal pain after RT	0.2 (0.3)	0.2 (0.4)
Constipation during RT	0.2 (0.3)	0.2 (0.3)
Constipation after RT	0.1 (0.3)	0.1 (0.2)
Diarrhea during RT	0.8 (0.7)	0.6 (0.6)
Diarrhea after RT	0.3 (0.4)	0.3 (0.4)
Rectal bleeding during RT	0.2 (0.3)	0.2 (0.3)
Rectal bleeding after RT	0.1 (0.3)	0.1 (0.2)

5. Secondary Outcome

Title	Percentage of Patients in Each Arm That Experience Tenesmus, Abdominal Pain, Constipation, Diarrhea and Rectal Bleeding During and After RT
Description	The number of patients that reported any grade 1 or higher adverse event was divided by the total number of patients evaluated. The analysis was done separately for each of the 5 outcomes and separately during RT and after RT.
Time Frame	During radiation therapy and up to 6 weeks post radiation therapy

Outcome Measure Data

Analysis Population Description

Two patients in Arm I and one patient from Arm II were not included in the endpoint analyses due to cancellations and protocol violations. 42 patients from each arm started RT and were used in that portion of the analysis. 25 patients from Arm I and 29 patients from Arm II were evaluated after RT. Two patients from Arm 1 provided incomplete data.

Arm/Group Title	Arm I: Sulfasalazine	Arm II: Placebo
Arm/Group Description	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
Measure Participants	42	42
Tenesmus during RT	35.7 85%	28.6 68.1%
Tenesmus after RT	11.9 28.3%	19.1 45.5%
Abdominal pain during RT	47.6 113.3%	38.1 90.7%
Abdominal pain after RT	19.1 45.5%	11.9 28.3%
Constipation during RT	38.1 90.7%	35.7 85%
Constipation after RT	14.3 34%	16.7 39.8%
Diarrhea during RT	76.2 181.4%	73.8 175.7%
Diarrhea after RT	33.3 79.3%	35.7 85%
Rectal bleeding during RT	38.1 90.7%	47.6 113.3%
Rectal bleeding after RT	11.9 28.3%	4.8 11.4%

6. Secondary Outcome

Title	Percent of Patients in Each Arm That Recorded "Yes" to Each of Questions 2-10 on the Bowel Function Questionnaire
Description	Questions that were used in this analysis: 2. Have you had a problem causing you to get up at night to have a bowel movement? 3. Have you had a problem causing you to lose control of your bowel movements? 4. Have you had a problem causing you to have a bowel movement within 30 minutes of a prior bowel movement? 5. Have you had to wear protective clothing or a pad in case you lost control of a bowel movement? 6. Have you had a problem causing you to be unable to tell the difference between stool and gas? 7. Have you had a problem causing you to have stools that are liquid? 1=yes 2=no q08 8. Have you found that once you feel the urge to have a bowel movement, you must do so within 15 minutes to avoid an accident? 9. Have you had cramping with a bowel movement? 10. Have you had blood in your bowel movement?
Time Frame	Up to 6 weeks post radiation therapy

Outcome Measure Data

Analysis Population Description

All patients that completed the questionnaire were included in the analysis. Questionnaires used were completed during the last week during RT and 6 weeks after RT.

Arm/Group Title	Arm I: Sulfasalazine	Arm II: Placebo
Arm/Group Description	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
Measure Participants	39	41
During RT : Q2	19 45.2%	10 23.8%
During RT : Q3	11 26.2%	10 23.8%
During RT : Q4	33 78.6%	33 78.6%
During RT : Q5	7 16.7%	0 0%
During RT : Q6	26 61.9%	23 54.8%
During RT : Q7	11 26.2%	20 47.6%
During RT : Q8	44 104.8%	43 102.4%
During RT : Q9	4 9.5%	17 40.5%
During RT : Q10	7 16.7%	7 16.7%
After RT : Q2	39 92.9%	27 64.3%
After RT : Q3	24 57.1%	22 52.4%
After RT : Q4	55 131%	56 133.3%
After RT : Q5	18 42.9%	12 28.6%
After RT : Q6	37 88.1%	46 109.5%
After RT : Q7	37 88.1%	37 88.1%
After RT : Q8	70 166.7%	61 145.2%
After RT : Q9	34 81%	34 81%
After RT : Q10	50 119%	29 69%

7. Secondary Outcome

Title	Percentage of Patients in Each Arm That Require Any Type of Antidiarrheal Medications.
Description	The number of patients reporting the use of anti-diarrheal medications divided by the number of patients evaluated for this endpoint.
Time Frame	Up to 24 months post radiotherapy

Outcome Measure Data

Analysis Population Description

Two patients in Arm I and one patient from Arm II were not included in the endpoint analyses due to cancellations and protocol violations.

Arm/Group Title	Arm I: Sulfasalazine	Arm II: Placebo
Arm/Group Description	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
Measure Participants	42	42
Number [percentage of participants]	48.7 116%	28.6 68.1%

8. Secondary Outcome

Title	Percentage of Patients in Each Arm That Experience Clinically Significant Deficits in Overall Quality of Life and Fatigue
Description	For each arm, the percentage of patients experience clinically significant deficits in overall QOL and fatigue as indicated by a score of 5 or lower on the 0-10 scale. The analysis was done using the questionnaire that was completed during the first week of radiotherapy (RT) and 6 weeks after RT.
Time Frame	Up to 6 weeks post radiotherapy

Outcome Measure Data

Analysis Population Description

All completed QOL questionnaires were included in the analysis. Questionnaires used were completed during the first week during RT and 6 weeks after RT. From Arm I, 41 patients completed questionnaires, 39 during and 26 after RT. For Arm II, 42 patients completed the questions, 40 during and 29 after RT.

Arm/Group Title	Arm I: Sulfasalazine	Arm II: Placebo
Arm/Group Description	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.	Patients receive two oral placebo tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
Measure Participants	41	42
During RT	17.9 42.6%	7.5 17.9%
After RT	26.9 64%	27.6 65.7%

Adverse Events

Arm/Group Title	Arm I: Sulfasalazine		Arm II: Placebo
Arm/Group Description	Patients receive two 500 mg oral sulfasalazine tablets twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.		placebo: Given orally
All Cause Mortality
	Arm I: Sulfasalazine		Arm II: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I: Sulfasalazine		Arm II: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/43 (2.3%)		2/42 (4.8%)
Blood and lymphatic system disorders
Anemia	0/43 (0%)	0	1/42 (2.4%)	1
Gastrointestinal disorders
Abdominal pain	1/43 (2.3%)	1	0/42 (0%)	0
Constipation	0/43 (0%)	0	1/42 (2.4%)	1
Gastrointestinal disorders - Other, specify	0/43 (0%)	0	1/42 (2.4%)	1
Tenesmus	0/43 (0%)	0	1/42 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Arm I: Sulfasalazine		Arm II: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/43 (97.7%)		40/42 (95.2%)
Blood and lymphatic system disorders
Anemia	15/43 (34.9%)	53	17/42 (40.5%)	82
Cardiac disorders
Sick sinus syndrome	1/43 (2.3%)	2	0/42 (0%)	0
Gastrointestinal disorders
Abdominal pain	15/43 (34.9%)	56	22/42 (52.4%)	68
Anal pain	1/43 (2.3%)	1	0/42 (0%)	0
Constipation	15/43 (34.9%)	40	15/42 (35.7%)	57
Diarrhea	33/43 (76.7%)	150	32/42 (76.2%)	154
Dyspepsia	1/43 (2.3%)	2	1/42 (2.4%)	1
Gastrointestinal disorders - Other, specify	0/43 (0%)	0	1/42 (2.4%)	1
Lower gastrointestinal hemorrhage	17/43 (39.5%)	44	15/42 (35.7%)	40
Mucositis oral	1/43 (2.3%)	1	0/42 (0%)	0
Nausea	2/43 (4.7%)	5	2/42 (4.8%)	2
Rectal pain	2/43 (4.7%)	6	0/42 (0%)	0
Tenesmus	17/43 (39.5%)	43	16/42 (38.1%)	49
General disorders
Fatigue	3/43 (7%)	9	2/42 (4.8%)	6
Immune system disorders
Allergic reaction	0/43 (0%)	0	1/42 (2.4%)	1
Infections and infestations
Abdominal infection	1/43 (2.3%)	1	0/42 (0%)	0
Rash pustular	1/43 (2.3%)	2	0/42 (0%)	0
Vaginal infection	1/43 (2.3%)	1	1/42 (2.4%)	2
Injury, poisoning and procedural complications
Dermatitis radiation	1/43 (2.3%)	1	1/42 (2.4%)	3
Investigations
Lymphocyte count decreased	2/43 (4.7%)	2	7/42 (16.7%)	33
Neutrophil count decreased	4/43 (9.3%)	5	6/42 (14.3%)	14
Platelet count decreased	4/43 (9.3%)	11	8/42 (19%)	15
White blood cell decreased	8/43 (18.6%)	22	18/42 (42.9%)	57
Metabolism and nutrition disorders
Hypocalcemia	0/43 (0%)	0	1/42 (2.4%)	1
Hypokalemia	0/43 (0%)	0	1/42 (2.4%)	2
Hyponatremia	0/43 (0%)	0	1/42 (2.4%)	1
Musculoskeletal and connective tissue disorders
Pain in extremity	0/43 (0%)	0	1/42 (2.4%)	5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	0/43 (0%)	0	1/42 (2.4%)	1
Nervous system disorders
Dizziness	0/43 (0%)	0	1/42 (2.4%)	1
Headache	1/43 (2.3%)	1	0/42 (0%)	0
Peripheral sensory neuropathy	0/43 (0%)	0	1/42 (2.4%)	5
Syncope	1/43 (2.3%)	1	0/42 (0%)	0
Renal and urinary disorders
Cystitis noninfective	1/43 (2.3%)	1	0/42 (0%)	0
Hematuria	1/43 (2.3%)	2	0/42 (0%)	0
Urinary frequency	1/43 (2.3%)	1	0/42 (0%)	0
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome	0/43 (0%)	0	1/42 (2.4%)	1
Rash acneiform	0/43 (0%)	0	1/42 (2.4%)	1
Rash maculo-papular	0/43 (0%)	0	2/42 (4.8%)	2
Urticaria	0/43 (0%)	0	1/42 (2.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.