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

• Number of Stools per day [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
• Chemotherapy dose reductions and delays due to diarrhea [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
• Quality of life as assessed by the MD Anderson Symptom Inventory [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

• Stools per day [ Designated as safety issue: No ]
• Chemotherapy dose reductions and delays due to diarrhea [ Designated as safety issue: Yes ]
• Safety as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
• Quality of life as assessed by the MD Anderson Symptom Inventory [ Designated as safety issue: No ]

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.

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.

• Chemotherapeutic Agent Toxicity
• Colorectal Cancer
• Diarrhea

• Drug: calcium aluminosilicate anti-diarrheal
  Given orally
• Other: placebo
  Given orally

• Experimental: Arm I: CASAD
  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.
  Intervention: Drug: calcium aluminosilicate anti-diarrheal
• Placebo Comparator: Arm II: Placebo
  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.
  Intervention: Other: placebo

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