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

M.D. Anderson Cancer Center

Status and phase: Completed; Phase 2

Conditions: Chemotherapeutic Agent Toxicity; Diarrhea; Colorectal Cancer

Treatments: Drug: calcium aluminosilicate anti-diarrheal; Other: placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00748215

MDA-2008-0005

CDR0000612205 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 100 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Triple Blind

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100 participants in 2 patient groups, including a placebo group

Arm I: CASAD

Experimental group

Description:

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.

Treatment:

Drug: calcium aluminosilicate anti-diarrheal

Arm II: Placebo

Placebo Comparator group

Description:

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.

Treatment:

Other: placebo