Evaluation of Octreotide LAR in Prevention of Chemotherapy-induced Diarrhea

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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LARCID: Evaluation of Octreotide LAR in Prevention of Chemotherapy-induced Diarrhea

Conditions
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Chemotherapy-induced Diarrhea

Intervention / Treatment
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* Drug: Octreotide Long Acting Release
* Other: Standard Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Providing a written informed consent Age between 18 and 80 years; 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); 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; A performance status of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale Adequate organ function and lab values within specific ranges Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration; 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; No prior use of octreotide in any formulation. Exclusion criteria: Use of concomitant antineoplastic treatments, other than regimens containing either 5-FU, capecitabine, or irinotecan with or without oxaliplatin, bevacizumab, or cetuximab; Previous or concomitant need for radiotherapy to the abdomen or pelvis; Indication of treatment, according to the judgment of the investigator, with erlotinib, gefitinib, panitumumab, or other EGFR-inhibitors other than cetuximab; 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); 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; 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; Active and ongoing systemic infection; Serious uncontrolled psychiatric illness; Ongoing pregnancy or lactation; Female patients who are pregnant or lactating, or are of childbearing potential and would not practice a medically acceptable method for birth control; 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; Use of any investigational agent within 30 days prior to enrollment in the study or foreseen use of an investigational agent during the study; History of chronic (≥ 30 nonconsecutive days) use of laxatives; Concurrent use of antidiarrheal agents; Inability to comply with the study protocol. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Octreotide Long Acting Release<br>Prevention of Chemotherapy Induced Diarrhea (CID) | Drug: Octreotide Long Acting Release<br>* Patients 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 first-line chemotherapy is discontinued or for a maximum of six doses of Octreotide LAR, whichever occurs first.<br>* Other names: Sandostatin LAR;|
| Other: Standard Treatment<br>Physician treatment of choice for chemotherapy induced diarrhea other than Octreotide LAR. | Other: Standard Treatment<br>* Physician treatment of choice for chemotherapy induced diarrhea other than Octreotide LAR.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Developing Diarrhea (Grade 1 to 4) | The percentage of patients developing diarrhea (incidence of grade 1 to 4) during treatment, considering only the worst grade of diarrhea for each patient. Diarrhea was graded according to Common Toxicity Criteria where Grade 0=None, 1 = Increase of <4 stools/day over pretreatment, Grade 2 = Increase of 4-6 stools/day, or nocturnal stools, Grade 3 = Increase of ≥7 stools/day or incontinence; or need for parenteral support for dehydration and Grade 4= Physiologic consequences requiring intensive care; or hemodynamic collapse. | 6 month overall | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Episodes of Diarrhea by Patient | Number of episodes of diarrhea is evaluated by patient diaries recorded on a daily basis. | 6 months overall | 
| Number of Episodes of Diarrhea by Patient by Cycle | Mean number of episodes of diarrhea is evaluated by patient diaries recorded by cycle. (cycle 1 to cycle 7.) | at each cycle (28 days per cycle) | 
| Percentage of Patients by Grade of Diarrhea | Grade (severity) of episodes of diarrhea is evaluated by patient diaries recorded on a daily basis by considering only worse grade of diarrhea for each patient. Diarrhea was graded according to Common Toxicity Criteria where Grade 0 = None, 1 = Increase of <4 stools/day over pretreatment, Grade 2 = Increase of 4-6 stools/day, or nocturnal stools, Grade 3 = Increase of ≥7 stools/day or incontinence; or need for parenteral support for dehydration and Grade 4= Physiologic consequences requiring intensive care; or hemodynamic collapse. | 6 months overall | 
| Percentage of Episodes by Grade | Grade (severity)of episodes of diarrhea is evaluated by patient diaries recorded on a daily basis by considering only worse grade of diarrhea for each patient. Diarrhea was graded according to Common Toxicity Criteria where Grade 1 = Increase of <4 stools/day over pretreatment, Grade 2 = Increase of 4-6 stools/day, or nocturnal stools, Grade 3 = Increase of ≥7 stools/day or incontinence;or need for parenteral support for dehydration and Grade 4= Physiologic consequences requiring intensive care; or hemodynamic collapse. | 6 months overall | 
| Percentage of Participants Who Need Chemotherapy Dose Reduction Due to Diarrhea | For patient, chemotherapy dose reduction due to diarrhea as counted each time it occurred. Chemotherapy dose reduction because of other adverse events related to chemotherapy was not considered. | 6 months overall | 
| Percentage of Participants Who Need Opioids for Control of Diarrhea |  | 6 months overall | 
| Percentage of Patients Hospitalized Due to Diarrhea |  | 6 months overall | 
| Percentage of Participants Who Need Intravenous Hydration for Control of Diarrhea |  | 6 months overall | 
| Percentage of Participants With Complete or Partial Response at Response Evaluation Criteria in Solid Tumors (RECIST) | Lesions that can be accurately measured in at least one dimension (longest diameter (LD) to be recorded) as > 20 mm with conventional techniques (CT, MRI) or as > 10 mm with spiral CT scan. All measurable lesions up to maximum of 5 lesions per organ and 10 lesions in total representative of all involved organs should be identified as target lesions and recorded and measured at baseline. Complete Response is defined as Disappearance of all target lesions. Partial Response is defined at least a 30% decrease in the sum of LD of target lesions taking as reference the baseline sum LD. | Day 56, Day 84, Day 112, Day 140, Day 168 | 
| Change From Baseline in Quality of Life Measured by the Functional Assessment of Chronic Illness Therapy-Diarrhea (FACIT-D) | Quality of life (QoL) is evaluated using FACIT-D scale. FACIT-D is composed of 38 items, whose responses range from 0 to 4. The total FACIT-D score may range from 0 to 152. The 38 items compose five subscales, each evaluating a different component of the (QOL). For calculating the subscale score, some items are computed in a reverse fashion, so that higher FACIT-D scores indicate a better (QoL). Descriptive statistics (mean, standard deviation, median, minimum and maximum) are used to summarize FACIT-D scores (total and subscales) by study group at each time point. | Baseline to Day 168 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal cancer, diarrhea, drug therapy, octreotide, fluorouracil, irinotecan, capecitabine, prevention