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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01198145
First received: September 8, 2010
Last updated: February 16, 2017
Last verified: February 2017
  Purpose

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 Intervention Phase
Diarrhea
Gastrointestinal Complications
Unspecified Adult Solid Tumor, Protocol Specific
Drug: sulfasalazine
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Maximum Severity of Diarrhea Toxicity as Measured by the CTCAE v4.0 During and After Radiotherapy (RT) [ Time Frame: 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:
  • Maximum Severity of Each Outcome Variable (Rectal Bleeding, Abdominal Cramping, Tenesmus, Constipation, and Diarrhea) Measured During and After RT [ Time Frame: 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.


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

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

  • Percentage of Patients in Each Arm That Experience Tenesmus, Abdominal Pain, Constipation, Diarrhea and Rectal Bleeding During and After RT [ Time Frame: 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.

  • Percent of Patients in Each Arm That Recorded "Yes" to Each of Questions 2-10 on the Bowel Function Questionnaire [ Time Frame: 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?


  • Percentage of Patients in Each Arm That Require Any Type of Antidiarrheal Medications. [ Time Frame: 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.

  • Percentage of Patients in Each Arm That Experience Clinically Significant Deficits in Overall Quality of Life and Fatigue [ Time Frame: 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.


Enrollment: 87
Study Start Date: April 2011
Study Completion Date: November 2016
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01198145

  Show 257 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: Robert C. Miller, MD Mayo Clinic
  More Information

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT01198145     History of Changes
Other Study ID Numbers: NCCTG-N08C9
NCI-2011-02602 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
CDR0000684240 ( Registry Identifier: PDQ (Physician Data Query) )
Study First Received: September 8, 2010
Results First Received: November 28, 2016
Last Updated: February 16, 2017

Keywords provided by Alliance for Clinical Trials in Oncology:
diarrhea
gastrointestinal complications
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Diarrhea
Signs and Symptoms, Digestive
Signs and Symptoms
Sulfasalazine
Anti-Infective Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on April 26, 2017