Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Octreotide in the Prevention of Diarrhea in Patients Receiving Irinotecan for Metastatic Colon Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Supportive care, Treatment Closed 18 and over Pharmaceutical / Industry NOVARTIS-CSMS995US05 NCT00006269

Objectives

I. Compare the incidence of grade 2-4 diarrhea after completion of irinotecan 
in patients with metastatic colorectal cancer treated with octreotide vs 
placebo.

II. Compare the duration of diarrhea and need for irinotecan dose reduction/ 
delay and hospitalization in patients treated with these 2 regimens.

III. Collect data on tumor response and 1 year survival in patients treated 
with these 2 regimens.

IV. Determine the pharmacokinetics and interaction of irinotecan and 
octreotide in a subset of these patients.

Entry Criteria

Disease Characteristics:

Histologically, cytologically, and/or radiographically proven metastatic
colorectal cancer with disease recurrence or progression following
fluorouracil (5-FU) based chemotherapy 
 Acceptable 5-FU based regimens include capecitabine, 5-FU-uracil,
  floxuridine, S-1, or eniluracil combined with 5-FU
 Acceptable 5-FU modulating agents include levamisole and leucovorin
  calcium
 
Measurable or evaluable disease

No known brain or leptomeningeal disease except previously irradiated lesions
that do not require corticosteroids and are asymptomatic

Prior/Concurrent Therapy:

Biologic therapy:
 Not specified

Chemotherapy:
 See Disease Characteristics
 No prior irinotecan
 At least 7 days since other prior chemotherapy and recovered

Endocrine therapy:
 See Disease Characteristics

Radiotherapy:
 See Disease Characteristics

Surgery:
 No ostomy

Other:
 Greater than 1 month since prior investigational agent
 No concurrent investigational agent
 No concurrent phenytoin, phenobarbital, valproic acid, or other antiepileptic
  therapy

Patient Characteristics:

Age:
 18 and over

Performance status:
 ECOG 0-2

Life expectancy:
 At least 12 weeks

Hematopoietic:
 WBC at least 3,000/mm3
 Granulocyte count at least 1,500/mm3
 Platelet count at least 100,000/mm3
 Hemoglobin at least 9 g/dL

Hepatic:
 Bilirubin no greater than 2 times upper limit of normal (ULN)
 SGOT or SGPT no greater than 3 times ULN (no greater than 5 times ULN if
  liver metastases present)

Renal:
 Creatinine less than 2.0 mg/dL

Cardiovascular:
 No uncontrolled hypertension
 No unstable angina
 No congestive heart failure
 No myocardial infarction within the past 6 months
 No serious cardiac arrhythmia 

Pulmonary:
 No interstitial pneumonia or fibrosis
 
Gastrointestinal:
 No symptomatic cholelithiasis
 No gastrointestinal disease that may result in nontherapy related
  diarrhea

Other:
 Not pregnant or nursing
 Negative pregnancy test
 Fertile patients must use effective contraception
 No other medical or surgical disease that may result in nontherapy related
  diarrhea
 No other severe disease that would preclude study
 No mental incapacity or psychiatric illness that would preclude study
 No uncontrolled diabetes mellitus
 No hypersensitivity to octreotide or any of its excipients
 No active or uncontrolled infection
 HIV negative
 No active second malignancy within the past 5 years except nonmelanomatous
  skin cancer or cervical carcinoma in situ of the cervix

Expected Enrollment

A total of 300 patients (150 per arm) will be accrued for this study.

Outline

This is a randomized, double blind, placebo controlled, multicenter study.  
Patients are stratified according to prior pelvic irradiation (yes vs no), age 
(under 70 vs 70 and over), and ECOG performance status (0 vs 1 or 2).

Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive octreotide intramuscularly (IM) once.  Beginning 10-14 
days later, patients receive irinotecan IV over 90 minutes on day 1.  Patients 
also receive octreotide IM on the same day as irinotecan.

Arm II: Patients receive placebo IM once.  Beginning 10-14 days later, 
patients receive irinotecan as in arm I.  Patients also receive placebo IM on 
the same day as irinotecan.

Therapy continues every 3 weeks for at least 6 courses in the absence of 
disease progression or unacceptable toxicity.

Patients are followed every 3 months through year 1.

Trial Contact Information

Trial Lead Organizations

Novartis Pharmaceuticals Corporation

Kurt Sizer, MD, Protocol chair		Ph: 973-781-6770

Registry Information
Official Title		A Prospective, Randomized Trial of Sandostatin LAR Depot for the Prevention of Irinotecan-Induced Diarrhea in Patients with Metastatic Colorectal Cancer
Trial Start Date		1999-12-01
Registered in ClinicalTrials.gov		NCT00006269
Date Submitted to PDQ		2000-08-08
Information Last Verified		2001-03-01