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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology ( North Central Cancer Treatment Group )
ClinicalTrials.gov Identifier:
NCT01198145
First received: September 8, 2010
Last updated: August 6, 2013
Last verified: February 2013
  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: Double Blind (Subject, 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: Up to 6 weeks post radiation therapy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Maximum severity and the duration of maximum severity of each outcome variable (i.e., rectal bleeding, abdominal cramping, tenesmus, constipation, and diarrhea) measured during and after RT [ Time Frame: Up to 6 weeks post radiation therapy ] [ Designated as safety issue: Yes ]
  • 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: Up to 6 weeks post radiation therapy ] [ Designated as safety issue: Yes ]
  • Average score for each outcome variable [ Time Frame: Up to 6 weeks post radiation therapy ] [ Designated as safety issue: No ]
  • Percentage of patients in each arm that experience each outcome variable during and after RT [ Time Frame: Up to 6 weeks post radiation therapy ] [ Designated as safety issue: No ]
  • Long-term diarrhea severity grade [ Time Frame: Up to 24 months post radiation therapy ] [ Designated as safety issue: No ]
  • Long-term bowel function score [ Time Frame: Up to 24 months post radiotherapy ] [ Designated as safety issue: No ]
  • Percent of patients in each arm that recorded "yes" to each of questions 2-12 on the bowel function questionnaire [ Time Frame: Up to 24 months post radiotherapy ] [ Designated as safety issue: No ]
  • Percentage of patients in each arm that require any and each type of antidiarrheal medications [ Time Frame: Up to 24 months post radiotherapy ] [ Designated as safety issue: No ]
  • Percentage of patients in each arm that experience clinically significant deficits in overall quality of life and fatigue [ Time Frame: Up to 24 months post radiotherapy ] [ Designated as safety issue: No ]

Estimated Enrollment: 140
Study Start Date: April 2011
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral sulfasalazine twice daily during radiotherapy and for 4 weeks after completion of radiotherapy.
Drug: sulfasalazine
Given orally
Placebo Comparator: Arm II
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
Genders Eligible for Study:   Both
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
North Central Cancer Treatment Group
Investigators
Study Chair: Robert C. Miller, MD Mayo Clinic
Study Chair: Daniel A. Petereit, MD Rapid City Regional Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology ( North Central Cancer Treatment Group )
ClinicalTrials.gov Identifier: NCT01198145     History of Changes
Other Study ID Numbers: NCCTG-N08C9, NCI-2011-02602, CDR0000684240
Study First Received: September 8, 2010
Last Updated: August 6, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

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-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Anti-Infective Agents
Gastrointestinal Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 28, 2014