Prophylaxis of Diarrhea in Adult Cancer Patients Receiving Targeted Cancer Therapy

Summary

A 24-week, (two 12-week stages), randomized, placebo-controlled, double-blind study to evaluate the safety and efficacy of crofelemer in providing prophylaxis of diarrhea in adult patients with solid tumors treated with targeted cancer therapy-containing treatment regimens. Diarrhea grading will be done according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Patients will be randomized 1:1 to placebo or crofelemer and will be stratified by the type of targeted cancer therapy and the tumor type. Placebo and/or crofelemer will be dispensed at Visit 1/Day 1 with the concurrent start of the targeted cancer therapy regimen. The initial Stage I double-blind placebo-controlled primary treatment phase will occur over a 12-week period to accommodate approximately 3 cycle chemotherapy cancer treatment dosing-cycles. The Primary and Secondary Endpoints will be analyzed after the last patient last visit (LPLV) of Stage I. After completing the Stage I double-blind, placebo-controlled primary treatment phase, the subjects will have the option to remain on their assigned treatment arm and reconsented to enter into the Stage II extension phase. Reconsent will be required to enter into Stage II. For subjects who do not reconsent, visit 5 will be the last study visit.

Timeline

Start

2020-10-07

Primary completion

2023-08-07

Completion

2023-10-30

Publications

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• Background Engelking C, Rutledge DN, Ippoliti C, Neumann J, Hogan CM. Cancer-related diarrhea: a neglected cause of cancer-related symptom distress. Oncol Nurs Forum. 1998 Jun;25(5):859-60. No abstract available.
• Background Benson AB 3rd, Ajani JA, Catalano RB, Engelking C, Kornblau SM, Martenson JA Jr, McCallum R, Mitchell EP, O'Dorisio TM, Vokes EE, Wadler S. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol. 2004 Jul 15;22(14):2918-26. doi: 10.1200/JCO.2004.04.132.
• Background Di Fiore F, Van Cutsem E. Acute and long-term gastrointestinal consequences of chemotherapy. Best Pract Res Clin Gastroenterol. 2009;23(1):113-24. doi: 10.1016/j.bpg.2008.11.016.
• Background Carlotto A, Hogsett VL, Maiorini EM, Razulis JG, Sonis ST. The economic burden of toxicities associated with cancer treatment: review of the literature and analysis of nausea and vomiting, diarrhoea, oral mucositis and fatigue. Pharmacoeconomics. 2013 Sep;31(9):753-66. doi: 10.1007/s40273-013-0081-2.
• Background Bowen JM. Mechanisms of TKI-induced diarrhea in cancer patients. Curr Opin Support Palliat Care. 2013 Jun;7(2):162-7. doi: 10.1097/SPC.0b013e32835ec861.
• Background Crutchley RD, Miller J, Garey KW. Crofelemer, a novel agent for treatment of secretory diarrhea. Ann Pharmacother. 2010 May;44(5):878-84. doi: 10.1345/aph.1M658. Epub 2010 Apr 13.
• Background Cottreau J, Tucker A, Crutchley R, Garey KW. Crofelemer for the treatment of secretory diarrhea. Expert Rev Gastroenterol Hepatol. 2012 Feb;6(1):17-23. doi: 10.1586/egh.11.87.
• Background Tradtrantip L, Namkung W, Verkman AS. Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol Pharmacol. 2010 Jan;77(1):69-78. doi: 10.1124/mol.109.061051. Epub 2009 Oct 6.
• Background Holodniy M, Koch J, Mistal M, Schmidt JM, Khandwala A, Pennington JE, Porter SB. A double blind, randomized, placebo-controlled phase II study to assess the safety and efficacy of orally administered SP-303 for the symptomatic treatment of diarrhea in patients with AIDS. Am J Gastroenterol. 1999 Nov;94(11):3267-73. doi: 10.1111/j.1572-0241.1999.01535.x.
• Background DiCesare D, DuPont HL, Mathewson JJ, Ashley D, Martinez-Sandoval F, Pennington JE, Porter SB. A double blind, randomized, placebo-controlled study of SP-303 (Provir) in the symptomatic treatment of acute diarrhea among travelers to Jamaica and Mexico. Am J Gastroenterol. 2002 Oct;97(10):2585-8. doi: 10.1111/j.1572-0241.2002.06027.x.
• Background Mangel AW, Chaturvedi P. Evaluation of crofelemer in the treatment of diarrhea-predominant irritable bowel syndrome patients. Digestion. 2008;78(4):180-6. doi: 10.1159/000185719. Epub 2008 Dec 18.
• Background Pessi MA, Zilembo N, Haspinger ER, Molino L, Di Cosimo S, Garassino M, Ripamonti CI. Targeted therapy-induced diarrhea: A review of the literature. Crit Rev Oncol Hematol. 2014 May;90(2):165-79. doi: 10.1016/j.critrevonc.2013.11.008. Epub 2013 Dec 5.
• Background Macarthur RD, Hawkins TN, Brown SJ, Lamarca A, Clay PG, Barrett AC, Bortey E, Paterson C, Golden PL, Forbes WP. Efficacy and safety of crofelemer for noninfectious diarrhea in HIV-seropositive individuals (ADVENT trial): a randomized, double-blind, placebo-controlled, two-stage study. HIV Clin Trials. 2013 Nov-Dec;14(6):261-73. doi: 10.1310/hct1406-261.
• Background Nee J, Salley K, Ludwig AG, Sommers T, Ballou S, Takazawa E, Duehren S, Singh P, Iturrino J, Katon J, Lee HN, Rangan V, Lembo AJ. Randomized Clinical Trial: Crofelemer Treatment in Women With Diarrhea-Predominant Irritable Bowel Syndrome. Clin Transl Gastroenterol. 2019 Dec;10(12):e00110. doi: 10.14309/ctg.0000000000000110.

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