Octreotide in Preventing or Reducing Diarrhea in Patients Receiving Chemoradiotherapy for Anal or Rectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Octreotide may be effective in preventing or controlling diarrhea in patients who are undergoing chemoradiotherapy for anal or rectal cancer. It is not yet known whether octreotide is effective in treating diarrhea. PURPOSE: This randomized phase III trial is studying octreotide in preventing or reducing diarrhea in patients who are undergoing chemoradiotherapy for anal or rectal cancer.

Detailed Description
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OBJECTIVES: Primary Determine the ability of octreotide to prevent the incidence of moderate, severe, or life-threatening chemoradiotherapy-induced diarrhea (grades 2-4) in patients with anal or rectal cancer. Secondary Compare the quality of life of patients treated with this drug vs placebo. Compare the number of hospitalizations and use of antidiarrheal agents (e.g., Imodium®) related to diarrhea (or its complications) in patients treated with these drugs. Compare treatment delays and/or dose reductions (chemotherapy and radiotherapy) in patients treated with these drugs. OUTLINE: This is a double-blind, placebo-controlled, randomized, multicenter study. Patients are stratified according to radiotherapy dose (< 50 Gy vs ≥ 50 Gy), chemotherapy dose (bolus vs continuous), and gender. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive octreotide* intramuscularly (IM) 4-7 days before the start of chemoradiotherapy and on day 22 (± 3 days) during chemoradiotherapy. Arm II: Patients receive placebo* IM 4-7 days before the start of chemoradiotherapy and on day 22 (± 3 days) during chemoradiotherapy. NOTE: *Patients receive a total of 2 injections of octreotide or placebo In both arms, treatment continues in the absence of unacceptable toxicity. Quality of life is assessed at baseline, at the completion of chemoradiotherapy, and at 3, 6, 9, and 15 months from the start of chemoradiotherapy. Patients are followed at 3, 6, 9, and 15 months from the start of chemoradiotherapy. PROJECTED ACCRUAL: A total of 226 patients (113 per treatment arm) will be accrued for this study within 2 years.

Official Title
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A Randomized, Double Blind, Placebo-Controlled Phase III Study To Determine The Efficacy Of Sandostatin LAR® Depot (Octreotide Acetate) In Preventing Or Reducing The Severity Of Chemoradiation-Induced Diarrhea In Patients With Anal Or Rectal Cancer

Conditions
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Anal Cancer, Colorectal Cancer, Drug/Agent Toxicity by Tissue/Organ, Radiation Enteritis

Intervention / Treatment
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* Drug: octreotide acetate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed primary anal or rectal cancer No metastasis beyond the pelvic regional nodes Must be scheduled to receive chemoradiotherapy PATIENT CHARACTERISTICS: Age 18 and over Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic Liver function tests < 3 times upper limit of normal No prior hepatic disease Renal Not specified Gastrointestinal No prior chronic or acute regional enteritis No malabsorption syndrome No prior inflammatory bowel disease that may exacerbate the radiotherapy toxicity No grade 2 or greater uncontrollable diarrhea at baseline No prior cholecystitis or gallstones, unless a cholecystectomy has been performed No prior incontinence of stool Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No uncontrolled diabetes (e.g., fasting glucose > 250 mg/dL) No prior allergy or hypersensitivity to study drug or other related drug or compound No other medical condition or mental impairment that would preclude study treatment and compliance PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics Prior chemotherapy allowed Endocrine therapy At least 6 months since prior administration of any of the following: Glucocorticoid therapy Insulin sensitizers (e.g., metformin, pioglitazone, or rosiglitazone) Exogenous growth hormone therapy Radiotherapy See Disease Characteristics No prior pelvic radiotherapy No prior intensity-modulated radiotherapy No concurrent radiotherapy for abdominal cancer No concurrent hyperfractionated, split-course, or intensity-modulated radiotherapy No brachytherapy prior to or after completion of all external beam radiotherapy Surgery No prior abdominal-perineal resection or other surgical procedure leaving the patient without a functioning rectum No colostomy Other More than 30 days since other prior investigational drugs No prior octreotide for cancer therapy-related diarrhea No concurrent prophylactic antidiarrheal medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sandostatin LAR® Depot<br>Sandostatin LAR® Depot Pre-RT (between day -7 and day -4 of RT) and Day 22 (± 3 days) | Drug: octreotide acetate<br> <br> |
| Placebo Comparator: Placebo<br>Placebo Pre-RT (between day -7 and day -4 of RT) and Day 22 (± 3 days) | Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevention of the incidence of moderate, severe, or life-threatening diarrhea |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life |  |  | 
| Economic measures |  |  | 
| Validity of the Functional Alterations due to Changes in Elimination-Changes in Bowel Function, the Quality of Life-Radiation Therapy Instrument, and the Expand Prostate Index Composite-Bowel questionnaires |  |  | 
| Prevention of the incidence of severe or life-threatening (i.e., grade 3-5) diarrhea |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiation enteritis, drug/agent toxicity by tissue/organ, stage I rectal cancer, stage II rectal cancer, stage III rectal cancer, stage IIIA anal cancer, stage IIIB anal cancer, recurrent anal cancer, stage I anal cancer, stage II anal cancer, recurrent rectal cancer