Clinical trial NCT00748215: Calcium Aluminosilicate Anti-Diarrheal in Treating and Preventing Diarrhea in Patients With Metastatic Colorectal Cancer Receiving Irinotecan
Official title: Phase II, Randomized, Double Blind Comparison of CASAD vs. Placebo for the Treatment and Prevention of Diarrhea in Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chemotherapeutic Agent Toxicity
Colorectal Cancer
Diarrhea
Keywords: diarrhea
chemotherapeutic agent toxicity
recurrent colon cancer
recurrent rectal cancer
stage IV colon cancer
stage IV rectal cancer
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-09-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility 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

Primary outcomes:
measure: Number of Participants With Grade 3/4 Diarrhea
timeFrame: First 6 weeks from baseline in initial intervention with CASAD or PLACEBO
Secondary outcomes:
Other outcomes:
Locations:
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Brian K. Kee, MD
role: STUDY_CHAIR
affiliation: M.D. Anderson Cancer Center
name: Michael J. Fisch, MD, MPH, FACP
role: STUDY_CHAIR
References: