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

Primary Purpose

Diarrhea, Gastrointestinal Complications, Unspecified Adult Solid Tumor, Protocol Specific

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

sulfasalazine

placebo

About this trial

This is an interventional supportive care trial for Diarrhea focused on measuring diarrhea, gastrointestinal complications, unspecified adult solid tumor, protocol specific

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Mayo Clinic Hospital
Mayo Clinic Scottsdale
Aurora Presbyterian Hospital
Boulder Community Hospital
Penrose Cancer Center at Penrose Hospital
St. Anthony Central Hospital
Porter Adventist Hospital
Presbyterian - St. Luke's Medical Center
St. Joseph Hospital
Rose Medical Center
Swedish Medical Center
North Colorado Medical Center
Sky Ridge Medical Center
Hope Cancer Care Center at Longmont United Hospital
McKee Medical Center
St. Mary - Corwin Regional Medical Center
North Suburban Medical Center
Exempla Lutheran Medical Center
Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
Tunnell Cancer Center at Beebe Medical Center
CCOP - Christiana Care Health Services
MBCCOP - Medical College of Georgia Cancer Center
Kapiolani Medical Center at Pali Momi
Cancer Research Center of Hawaii
OnCare Hawaii, Incorporated - Lusitana
Queen's Cancer Institute at Queen's Medical Center
Straub Clinic and Hospital, Incorporated
Hawaii Medical Center - East
OnCare Hawaii, Incorporated - Kuakini
Kapiolani Medical Center for Women and Children
Tripler Army Medical Center
Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center
Rush-Copley Cancer Care Center
Louis A. Weiss Memorial Hospital
Ingalls Cancer Care Center at Ingalls Memorial Hospital
Trinity Cancer Center at Trinity Medical Center - 7th Street Campus
CCOP - Carle Cancer Center
Elkhart Clinic, LLC
Michiana Hematology-Oncology, PC - Elkhart
Elkhart General Hospital
St. Francis Hospital Cancer Care Services
Howard Community Hospital
Michiana Hematology-Oncology, PC - South Bend
Saint Joseph Regional Medical Center
Michiana Hematology Oncology PC - Plymouth
Reid Hospital & Health Care Services
CCOP - Northern Indiana CR Consortium
Memorial Hospital of South Bend
Michiana Hematology Oncology PC - La Porte
Cedar Rapids Oncology Associates
Mercy Regional Cancer Center at Mercy Medical Center
Medical Oncology and Hematology Associates - West Des Moines
Mercy Cancer Center - West Lakes
CCOP - Iowa Oncology Research Association
John Stoddard Cancer Center at Iowa Methodist Medical Center
Medical Oncology and Hematology Associates at John Stoddard Cancer Center
Medical Oncology and Hematology Associates at Mercy Cancer Center
Mercy Cancer Center at Mercy Medical Center - Des Moines
John Stoddard Cancer Center at Iowa Lutheran Hospital
Siouxland Hematology-Oncology Associates, LLP
Mercy Medical Center - Sioux City
St. Luke's Regional Medical Center
Methodist West Hospital
Cancer Center of Kansas, PA - Chanute
Cancer Center of Kansas, PA - Dodge City
Cancer Center of Kansas, PA - El Dorado
Cancer Center of Kansas - Fort Scott
Cancer Center of Kansas-Independence
Cancer Center of Kansas, PA - Kingman
Lawrence Memorial Hospital
Cancer Center of Kansas, PA - Liberal
Cancer Center of Kansas, PA - Newton
Cancer Center of Kansas, PA - Parsons
Cancer Center of Kansas, PA - Pratt
Cancer Center of Kansas, PA - Salina
Cancer Center of Kansas, PA - Wellington
Associates in Womens Health, PA - North Review
Cancer Center of Kansas, PA - Medical Arts Tower
Cancer Center of Kansas, PA - Wichita
CCOP - Wichita
Via Christi Cancer Center at Via Christi Regional Medical Center
Cancer Center of Kansas, PA - Winfield
Ochsner Cancer Institute at Ochsner Clinic Foundation
Union Hospital of Cecil County
Boston University Cancer Research Center
Hickman Cancer Center at Bixby Medical Center
Saint Joseph Mercy Cancer Center
CCOP - Michigan Cancer Research Consortium
Oakwood Cancer Center at Oakwood Hospital and Medical Center
Genesys Hurley Cancer Institute
Hurley Medical Center
Van Elslander Cancer Center at St. John Hospital and Medical Center
Foote Memorial Hospital
Sparrow Regional Cancer Center
St. Mary Mercy Hospital
Community Cancer Center of Monroe
Mercy Memorial Hospital - Monroe
St. Joseph Mercy Oakland
Mercy Regional Cancer Center at Mercy Hospital
Seton Cancer Institute at Saint Mary's - Saginaw
Lakeland Regional Cancer Care Center - St. Joseph
Lakeside Cancer Specialists, PLLC
St. John Macomb Hospital
MeritCare Bemidji
St. Joseph's Medical Center
Fairview Ridges Hospital
Mercy and Unity Cancer Center at Mercy Hospital
Essentia Health - Duluth Clinic
CCOP - Duluth
Miller - Dwan Medical Center
Fairview Southdale Hospital
Mercy and Unity Cancer Center at Unity Hospital
Hutchinson Area Health Care
Immanuel St. Joseph's
HealthEast Cancer Care at St. John's Hospital
Minnesota Oncology - Maplewood
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Hennepin County Medical Center - Minneapolis
Humphrey Cancer Center at North Memorial Outpatient Center
Mayo Clinic Cancer Center
CCOP - Metro-Minnesota
Park Nicollet Cancer Center
Regions Hospital Cancer Care Center
United Hospital
St. Francis Cancer Center at St. Francis Medical Center
Lakeview Hospital
Ridgeview Medical Center
Willmar Cancer Center at Rice Memorial Hospital
Minnesota Oncology - Woodbury
Central Care Cancer Center at Carrie J. Babb Cancer Center
Southeast Cancer Center
Goldschmidt Cancer Center
Missouri Baptist Cancer Center
CCOP - Cancer Research for the Ozarks
Hulston Cancer Center at Cox Medical Center South
CCOP - Montana Cancer Consortium
St. Vincent Healthcare Cancer Care Services
Hematology-Oncology Centers of the Northern Rockies - Billings
Billings Clinic - Downtown
Bozeman Deaconess Cancer Center
St. James Healthcare Cancer Care
Benefis Sletten Cancer Institute
St. Peter's Hospital
Kalispell Regional Medical Center
Montana Cancer Specialists at Montana Cancer Center
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
Cancer Resource Center - Lincoln
CCOP - Missouri Valley Cancer Consortium
Immanuel Medical Center
Alegant Health Cancer Center at Bergan Mercy Medical Center
Lakeside Hospital
Creighton University Medical Center
New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
New Hampshire Oncology - Hematology, PA - Hooksett
Lakes Region General Hospital
Cancer Institute of New Jersey at Cooper - Voorhees
University of New Mexico Cancer Center
University of New Mexico Cancer Center - South
Mount Kisco Medical Group, PC
Randolph Hospital
CaroMont Cancer Center at Gaston Memorial Hospital
Wayne Memorial Hospital, Incorporated
Moses Cone Regional Cancer Center at Wesley Long Community Hospital
Park Ridge Hospital
High Point Regional Hospital
Annie Penn Cancer Center
Iredell Memorial Hospital
Medcenter One Hospital Cancer Care Center
Mid Dakota Clinic, PC
St. Alexius Medical Center Cancer Center
MeritCare Broadway
Altru Cancer Center at Altru Hospital
Wood County Oncology Center
Adena Regional Medical Center
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Riverside Methodist Hospital Cancer Care
CCOP - Columbus
Grant Medical Center Cancer Care
Mount Carmel Health - West Hospital
Doctors Hospital at Ohio Health
Grandview Hospital
Good Samaritan Hospital
David L. Rike Cancer Center at Miami Valley Hospital
Samaritan North Cancer Care Center
CCOP - Dayton
Grady Memorial Hospital
Community Cancer Center
Hematology Oncology Center
Blanchard Valley Medical Associates
Middletown Regional Hospital
Wayne Hospital
Charles F. Kettering Memorial Hospital
Fairfield Medical Center
Lima Memorial Hospital
Strecker Cancer Center at Marietta Memorial Hospital
Northwest Ohio Oncology Center
Knox Community Hospital
Licking Memorial Cancer Care Program at Licking Memorial Hospital
St. Charles Mercy Hospital
Toledo Clinic - Oregon
Community Hospital of Springfield and Clark County
Flower Hospital Cancer Center
Mercy Hospital of Tiffin
Toledo Hospital
St. Vincent Mercy Medical Center
Medical University of Ohio Cancer Center
St. Anne Mercy Hospital
Toledo Clinic, Incorporated - Main Clinic
UVMC Cancer Care Center at Upper Valley Medical Center
Fulton County Health Center
Mount Carmel St. Ann's Cancer Center
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Genesis - Good Samaritan Hospital
Natalie Warren Bryant Cancer Center at St. Francis Hospital
Legacy Mount Hood Medical Center
Legacy Good Samaritan Hospital & Comprehensive Cancer Center
Legacy Meridian Park Hospital
AnMed Cancer Center
Bon Secours St. Francis Health System
Cancer Centers of the Carolinas - Faris Road
Greenville Hospital Cancer Center
CCOP - Greenville
Cancer Centers of the Carolinas - Seneca
CCOP - Upstate Carolina
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
Cancer Centers of the Carolinas - Spartanburg
Rapid City Regional Hospital
Avera Cancer Institute
Sanford Cancer Center at Sanford USD Medical Center
Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
Fredericksburg Oncology, Incorporated
Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County
Legacy Salmon Creek Medical Center
Edwards Comprehensive Cancer Center at Cabell Huntington Hospital
Center for Cancer Treatment & Prevention at Sacred Heart Hospital
Marshfield Clinic Cancer Care at Regional Cancer Center
Central Wisconsin Cancer Program at Agnesian HealthCare
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
Green Bay Oncology, Limited at St. Mary's Hospital
St. Mary's Hospital Medical Center - Green Bay
St. Vincent Hospital Regional Cancer Center
Gundersen Lutheran Center for Cancer and Blood
Holy Family Memorial Medical Center Cancer Care Center
Bay Area Cancer Care Center at Bay Area Medical Center
Marshfield Clinic - Marshfield Center
Saint Joseph's Hospital
Marshfield Clinic - Lakeland Center
Ministry Medical Group at Saint Mary's Hospital
Marshfield Clinic - Indianhead Center
St. Nicholas Hospital
Marshfield Clinic at Saint Michael's Hospital
Saint Michael's Hospital Cancer Center
Door County Cancer Center at Door County Memorial Hospital
Marshfield Clinic - Weston Center
Ministry Saint Clare's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I: Sulfasalazine

Arm II: Placebo

Arm Description

Patients receive oral sulfasalazine twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.

Patients receive oral placebo twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.

Outcomes

Primary Outcome Measures

Maximum Severity of Diarrhea Toxicity as Measured by the CTCAE v4.0 During and After Radiotherapy (RT)

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

Maximum Severity of Each Outcome Variable (Rectal Bleeding, Abdominal Cramping, Tenesmus, Constipation, and Diarrhea) Measured During and After RT

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.

Area Under the Curve That Combines the Individual Severity of Diarrhea Toxicity as Measured by the CTCAE v4.0 During and After RT

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.

Average Graded Severity for Tenesmus, Abdominal Pain, Constipation, Diarrhea and Hemorrhage During and After RT as Graded by CTCAE v4.0

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.

Percentage of Patients in Each Arm That Experience Tenesmus, Abdominal Pain, Constipation, Diarrhea and Rectal Bleeding During and After RT

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.

Percent of Patients in Each Arm That Recorded "Yes" to Each of Questions 2-10 on the Bowel Function Questionnaire

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?

Percentage of Patients in Each Arm That Require Any Type of Antidiarrheal Medications.

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

Percentage of Patients in Each Arm That Experience Clinically Significant Deficits in Overall Quality of Life and Fatigue

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.

Full Information

NCT ID

NCT01198145

First Posted

September 8, 2010

Last Updated

April 28, 2020

Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01198145

Brief Title

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

Official Title

Phase III, Randomized, Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

April 2020

Overall Recruitment Status

Completed

Study Start Date

April 2011 (Actual)

Primary Completion Date

July 22, 2013 (Actual)

Study Completion Date

July 15, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Alliance for Clinical Trials in Oncology

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diarrhea, Gastrointestinal Complications, Unspecified Adult Solid Tumor, Protocol Specific

Keywords

diarrhea, gastrointestinal complications, unspecified adult solid tumor, protocol specific

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

87 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I: Sulfasalazine

Arm Type

Experimental

Arm Description

Patients receive oral sulfasalazine twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.

Arm Title

Arm II: Placebo

Arm Type

Placebo Comparator

Arm Description

Patients receive oral placebo twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.

Intervention Type

Drug

Intervention Name(s)

sulfasalazine

Intervention Description

Given orally

Intervention Type

Other

Intervention Name(s)

placebo

Intervention Description

Given orally

Primary Outcome Measure Information:

Title

Maximum Severity of Diarrhea Toxicity as Measured by the CTCAE v4.0 During and After Radiotherapy (RT)

Description

Time Frame