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

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 3

Conditions: Unspecified Adult Solid Tumor, Protocol Specific; Diarrhea; Gastrointestinal Complications

Treatments: Drug: sulfasalazine; Other: placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01198145

NCI-2011-02602 (Registry Identifier)

CDR0000684240 (Registry Identifier)

NCCTG-N08C9

Details and patient eligibility

About

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.

Full 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.

Enrollment: 87 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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87 participants in 2 patient groups, including a placebo group

Arm I: Sulfasalazine

Experimental group

Description:

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

Treatment:

Drug: sulfasalazine

Arm II: Placebo

Placebo Comparator group

Description:

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

Treatment:

Other: placebo