Evaluation of Octreotide LAR in Prevention of Chemotherapy-induced Diarrhea

This study will evaluate the efficacy of Octreotide LAR in preventing chemotherapy-induced diarrhea (with regimens that contain 5 fluorouracil, irinotecan and capecitabine)in patients with colorectal cancer.

Eligible patients will have a diagnosis of colorectal cancer, and will be candidates to adjuvant chemotherapy or first-line chemotherapy for metastatic disease with a regimen containing fluorouracil, capecitabine and/or irinotecan. Eligible chemotherapy regimens include Irinotecan, Leucovorin (folinic acid), and Fluorouracil(IFL), Leucovorin, Fluorouracil, and Irinotecan (FOLFIRI), combinations of Irinotecan and Capecitabine, the Roswell Park regimen and the Mayo Clinic regimen, all of them without or with Oxaliplatin, Bevacizumab or Cetuximab. Patients receiving Erlotinib, or other Tyrosine-kinase, Epidermal Growth Factor Receptor (EGFR)-inhibitors, will not be eligible.

The acute treatment for diarrhea will be left to physician's discretion in both groups. Patients in the control arm will be treated without Octreotide LAR. Patients in the experimental arm will receive the first dose of Octreotide LAR (30 mg) at chemotherapy initiation, in addition to a minimum of two more identical monthly doses of Octreotide LAR (with an interval of 28 days between them), until chemotherapy is discontinued or for a maximum of six doses of Octreotide LAR, whichever occurs first. Patient evaluation will be done at each cycle for efficacy and toxicity.

Eligibility Criteria:
Inclusion criteria:

1. Providing a written informed consent
2. Age between 18 and 80 years;
3. Histological diagnosis of colorectal cancer, presence of metastatic disease and no prior systemic therapy for metastatic disease (prior adjuvant therapy will be allowed if completed 6 months or longer before inclusion in the study);
4. Indication of treatment, according to the judgment of the investigator, with a chemotherapy regimen containing either 5-FU, capecitabine, or irinotecan; any such regimen may also include oxaliplatin, bevacizumab, or cetuximab;
5. A performance status of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale
6. Adequate organ function and lab values within specific ranges
7. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration;
8. Fertile patients (male or female) must agree to use an acceptable method of contraception to avoid pregnancy for the duration of the study and for 3 months after study termination;
9. No prior use of octreotide in any formulation.

Exclusion criteria:

1. Use of concomitant antineoplastic treatments, other than regimens containing either 5-FU, capecitabine, or irinotecan with or without oxaliplatin, bevacizumab, or cetuximab;
2. Previous or concomitant need for radiotherapy to the abdomen or pelvis;
3. Indication of treatment, according to the judgment of the investigator, with erlotinib, gefitinib, panitumumab, or other EGFR-inhibitors other than cetuximab;
4. A second malignancy (except in situ carcinoma of the cervix, in situ carcinoma of the bladder, adequately treated basal-cell or squamous-cell carcinoma of the skin, or another malignancy treated more than 5 years prior to enrollment and without recurrence);
5. Any type of condition leading to chronic diarrhea, including, but not limited to inflammatory bowel disease (e.g., ulcerative colitis and Crohn's disease), chronic diarrhea of presumed or confirmed infectious origin, and irritable bowel syndrome;
6. Active or uncontrolled concurrent medical condition, including, but not limited to, unstable angina, congestive heart failure, coronary artery disease, hypertension, diabetes mellitus, and hyper- or hypothyroidism;
7. Active and ongoing systemic infection;
8. Serious uncontrolled psychiatric illness;
9. Ongoing pregnancy or lactation;
10. Female patients who are pregnant or lactating, or are of childbearing potential and would not practice a medically acceptable method for birth control;
11. Lesions that have been irradiated cannot be included as sites of measurable disease. If the only measurable lesion was previously irradiated the patient cannot be included;
12. Use of any investigational agent within 30 days prior to enrollment in the study or foreseen use of an investigational agent during the study;
13. History of chronic (≥ 30 nonconsecutive days) use of laxatives;
14. Concurrent use of antidiarrheal agents;
15. Inability to comply with the study protocol.

Other protocol-defined inclusion/exclusion criteria may apply.