Calcium Aluminosilicate Anti-Diarrheal in Treating and Preventing Diarrhea in Patients With Metastatic Colorectal Cancer Receiving Irinotecan

Study Overview
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Brief Summary
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RATIONALE: Calcium aluminosilicate anti-diarrheal (CASAD) may help treat and prevent diarrhea caused by irinotecan. It is not yet known whether CASAD is more effective than a placebo in treating and preventing diarrhea in patients receiving irinotecan. PURPOSE: This randomized phase II trial is studying CASAD to see how well it works compared with a placebo in treating and preventing diarrhea in patients with metastatic colorectal cancer receiving irinotecan.

Detailed Description
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OBJECTIVES: Primary To compare the efficacy of calcium aluminosilicate anti-diarrheal (CASAD) versus placebo in reducing the incidence of grade 3 or 4 diarrhea in patients with metastatic colorectal cancer receiving an irinotecan-based chemotherapy regimen. Secondary To compare stools per day in patients treated with these drugs. To compare chemotherapy dose reductions and delays due to diarrhea in patients treated with these drugs. To compare quality of life of patients treated with these drugs. To compare the safety of these drugs in these patients. To compare the incidence of grade 3 or 4 diarrhea in patients treated with these drugs. OUTLINE: This is a multicenter study. Patients are stratified according to chemotherapy regimen (irinotecan hydrochloride in combination with fluorouracil and/or biologic therapy vs irinotecan hydrochloride alone). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral calcium aluminosilicate anti-diarrheal (CASAD) 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients who develop grade 3 or 4 diarrhea and are removed from the study may receive CASAD for an additional 6 weeks. Arm II: Patients receive oral placebo 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients who develop grade 3 or 4 diarrhea and are removed from the study may then receive CASAD for 6 weeks. Patients undergo quality-of-life assessment at baseline and at weeks 3, 5, and 6. After completion of study treatment, patients are followed for 30 days.

Official Title
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Phase II, Randomized, Double Blind Comparison of CASAD vs. Placebo for the Treatment and Prevention of Diarrhea in Patients With Metastatic Colorectal Cancer

Conditions
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Chemotherapeutic Agent Toxicity, Colorectal Cancer, Diarrhea

Intervention / Treatment
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* Drug: calcium aluminosilicate anti-diarrheal
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of colorectal cancer Metastatic disease Scheduled to receive irinotecan hydrochloride alone or in combination with fluorouracil, cetuximab, leucovorin calcium, or other biological therapy (including bevacizumab) No uncontrolled brain metastasis Previously treated brain metastasis allowed PATIENT CHARACTERISTICS: Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Absolute neutrophil count (ANC) > 1,000/mm³ Platelet count > 100,000/mm³ Total bilirubin < 1.5 times upper limit of normal (ULN) Aspartate aminotransferase (AST or SGOT) and/or alanine aminotransferase (ALT or SGPT) < 2.5 times ULN (< 5 times ULN if liver metastasis is present) Alkaline phosphatase < 2.5 times ULN Creatinine clearance > 35 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known UDP-glucuronosyltransferase 1A1 (UGT1A1) deficiency with homozygotes. No known history of Gilbert's disease No diarrhea > grade 1 No serious illness or medical condition, including any of the following: Uncontrolled congestive heart failure Uncontrolled hypertension (i.e., blood pressure > 150/100 mm Hg) Uncontrolled arrhythmia Active angina pectoris Symptomatic heart disease according to New York Heart Association(NYHA) class II-IV No serious uncontrolled active infection No existing colostomy or ileostomy Not able to take and document oral study medications No history of allergies to irinotecan hydrochloride No history of significant neurological or psychiatric disorders that would preclude giving consent or participating in study treatment or follow up PRIOR CONCURRENT THERAPY: See Disease Characteristics Prior treatment for metastatic disease allowed At least 4 weeks since prior irinotecan More than 2 weeks since prior chemotherapy Irinotecan alone or in combination with other chemotherapy or biologic agents allowed More than 4 weeks since prior radiotherapy No concurrent radiotherapy No concurrent medication schedule that does not permit a 2-hour window between administration of calcium aluminosilicate anti-diarrheal (CASAD) and other medications

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I: CASAD<br>Oral calcium aluminosilicate anti-diarrheal (CASAD) 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Participants who develop grade 3 or 4 diarrhea may receive CASAD for an additional 6 weeks. | Drug: calcium aluminosilicate anti-diarrheal<br>* Given orally<br>|
| Placebo Comparator: Arm II: Placebo<br>Oral placebo 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Participants who develop grade 3 or 4 diarrhea may then receive CASAD for 6 weeks. | Other: placebo<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Grade 3/4 Diarrhea | One hundred patients were randomized equally between CASAD and placebo arms in order to assess whether CASAD was efficacious in preventing grade 3/4 diarrhea within 6 weeks for each arm compared. Bayesian futility monitoring in the study with a recommendation to stop the trial for futility if it became clear that CASAD was not better than placebo. | First 6 weeks from baseline in initial intervention with CASAD or PLACEBO | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diarrhea, chemotherapeutic agent toxicity, recurrent colon cancer, recurrent rectal cancer, stage IV colon cancer, stage IV rectal cancer