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Clinical Trial
. 2016 Jul 15;95(4):1168-74.
doi: 10.1016/j.ijrobp.2016.01.063. Epub 2016 Apr 23.

N08C9 (Alliance): A Phase 3 Randomized Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy

Robert C Miller  1 , Daniel G Petereit  2 , Jeff A Sloan  3 , Heshan Liu  3 , James A Martenson  4 , James D Bearden 3rd  5 , Ronald Sapiente  6 , Grant R Seeger  7 , Rex B Mowat  8 , Ben Liem  9 , Matthew J Iott  4 , Charles L Loprinzi  10 ; Alliance for Clinical Trials in Oncology
Affiliations
Clinical Trial

N08C9 (Alliance): A Phase 3 Randomized Study of Sulfasalazine Versus Placebo in the Prevention of Acute Diarrhea in Patients Receiving Pelvic Radiation Therapy

Robert C Miller et al. Int J Radiat Oncol Biol Phys. .

Abstract

Purpose: To provide confirmatory evidence on the use of sulfasalazine to reduce enteritis during pelvic radiation therapy (RT), following 2 prior single-institution trials suggestive that benefit existed.

Methods and materials: A multi-institution, randomized, double-blind, placebo-controlled phase 3 trial was designed to assess the efficacy of sulfasalazine versus placebo in the treatment of RT-related enteritis during RT including the posterior pelvis (45.0-53.5 Gy) and conducted through a multicenter national cooperative research alliance. Patients received 1000 mg of sulfasalazine or placebo orally twice daily during and for 4 weeks after RT. The primary endpoint was maximum severity of diarrhea (Common Terminology Criteria for Adverse Events version 4.0). Toxicity and bowel function were assessed by providers through a self-administered bowel function questionnaire taken weekly during RT and for 6 weeks afterward.

Results: Eighty-seven patients were enrolled in the trial between April 29, 2011, and May 13, 2013, with evenly distributed baseline factors. At the time of a planned interim toxicity analysis, more patients with grade ≥3 diarrhea received sulfasalazine than received placebo (29% vs 11%, P=.04). A futility analysis showed that trial continuation would be unlikely to yield a positive result, and a research board recommended halting study treatment. Final analysis of the primary endpoint showed no significant difference in maximum diarrhea severity between the sulfasalazine and placebo arms (P=.41).

Conclusions: Sulfasalazine does not reduce enteritis during pelvic RT and may be associated with a higher risk of adverse events than placebo. This trial illustrates the importance of confirmatory phase 3 trials in the evaluation of symptom-control agents.

Trial registration: ClinicalTrials.gov NCT01198145.

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Figures

Fig. 1
Fig. 1
CONSORT (Consolidated Standards of Reporting Trials) diagram. Abbreviation: AE = adverse event.
See this image and copyright information in PMC

References

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