Evaluation of Octreotide LAR in Prevention of Chemotherapy-induced Diarrhea (LARCID)

LARCID: 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.

Study Overview

• Status: Completed
• Conditions: Chemotherapy-induced Diarrhea
• Intervention / Treatment: Drug: Octreotide Long Acting Release; Other: Standard Treatment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Belo Horizonte, Brazil
    • BioCancer
  • Florianópolis, Brazil
    • CEPON-Centro de Pesquisas Oncológicas
  • Porto Alegre, Brazil
    • Hospital Sao Lucas- Faculdade de Medicina da PUCRS
  • Salvador, Brazil
    • Nucleo de Oncologia da Bahia
  • Salvador, Brazil
    • Clínica AMO
  • Santo André, Brazil
    • Faculdade de Medicina do ABC
  • São Paulo, Brazil
    • Hosital Alemão Oswaldo Cruz
  • São Paulo, Brazil
    • Hospital A C Camargo/ Fundação Antonio Prudente
  • São Paulo, Brazil
    • Hospital das Clinicas - FMUSP
  • São Paulo, Brazil
    • Instituto Arnaldo Vieira de Carvalho - IAVC
  • São Paulo, Brazil
    • UNIFESP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Octreotide Long Acting Release; Prevention of Chemotherapy Induced Diarrhea (CID)	Drug: Octreotide Long Acting Release; 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.; Other Names: Sandostatin LAR; Octreotide LAR
Other: Standard Treatment; Physician treatment of choice for chemotherapy induced diarrhea other than Octreotide LAR.	Other: Standard Treatment; Physician treatment of choice for chemotherapy induced diarrhea other than Octreotide LAR.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Hoff PM, Saragiotto DF, Barrios CH, del Giglio A, Coutinho AK, Andrade AC, Dutra C, Forones NM, Correa M, Portella Mdo S, Passos VQ, Chinen RN, van Eyll B. Randomized phase III trial exploring the use of long-acting release octreotide in the prevention of chemotherapy-induced diarrhea in patients with colorectal cancer: the LARCID trial. J Clin Oncol. 2014 Apr 1;32(10):1006-11. doi: 10.1200/JCO.2013.50.8077. Epub 2014 Feb 10.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: December 21, 2007
• First Submitted That Met QC Criteria: December 21, 2007
• First Posted (Estimate): December 28, 2007

Study Record Updates

• Last Update Posted (Estimate): May 4, 2015
• Last Update Submitted That Met QC Criteria: April 13, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: capecitabine; Colorectal cancer; diarrhea; prevention; irinotecan; fluorouracil; octreotide; drug therapy
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Octreotide
• Other Study ID Numbers: CSMS995AIC04