A phase II, randomized, double blind comparison of calcium aluminosilicate clay (CASAD) versus placebo (dibasic calcium carbonate) for the prevention of diarrhea in patients (pts) with metastatic colorectal cancer (mCRC) treated with irinotecan (I).
3600 Background: CASAD is a naturally occurring calcium montmorrilonite clay that serves as a cation exchange absorbent. One of the active metabolites of Irinotecan is SN-38, which is adsorbed by CASAD in vitro. The study hypothesis was that oral CASAD would reduce the rate of grade 3/4 diarrhea in mCRC patients treated with irinotecan. Methods: The study is a multicenter, prospective, randomized, double blinded placebo-controlled phase II trial. One hundred patients receiving I-based chemotherapy were randomized equally between CASAD (1000 mg po 4x daily) and placebo in order to have 75% power to detect a difference in the proportions of patients with grade 3/4 diarrhea within 6 weeks at a 1-sided 5% significance level. We also compared symptom burden using the MDASI questionnaire summed over the 13 symptom items for weeks 0, 3, 5, and 6. Results: Between 5/2009 and 5/2012, 100 patients were randomized in a 1:1 ratio between study arms. Median age 57 yrs, 54% male, 74% Non-Hispanic White, 93% performance status 0 or 1. Serious diarrhea was less frequent than expected based upon prior studies with Irinotecan. In evaluable patients, no significant difference in the rate of G3/4 diarrhea was seen (the primary endpoint): CASAD arm: 7/43 pts (16%), Placebo arm: 3/32 pts (9%), p=0.70. The rate of any diarrhea among all pts was also similar: CASAD arm 64% vs. Placebo arm 70%. The rate of study dropout was 14% in CASAD and 38% for placebo (p=0.01; 2-sided). No differences were found in symptom burden or individual symptom items or serious adverse events. Conclusions: Compared with placebo, CASAD use was safe but ineffective in preventing diarrhea in mCRC patients treated with irinotecan-containing chemotherapy regimens. There were no favorable or unfavorable signals in terms of the patient experience related to symptoms, but there were significantly more dropouts in the placebo arm. Future CASAD trials are focused on active treatment of diarrhea. Clinical trial information: NCT00748215.