Chemotherapy-induced DiarrheaPhase 3LARCIDNCT00582426
Evaluation of Octreotide LAR in Prevention of Chemotherapy-induced Diarrhea
A Phase 3 study testing Octreotide Long Acting Release and Standard Treatment in people with Chemotherapy-induced Diarrhea, run by Novartis Pharmaceuticals at 11 sites in Brazil.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Chemotherapy-induced Diarrhea
- What is being tested?
- Octreotide Long Acting Release and Standard Treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 139 participants
- Where
- 11 sitesBrazil
- Study dates
- Apr 2008to Sep 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Brazil11 sites
Biocâncer
Belo Horizonte
CEPON-Centro de Pesquisas Oncologicas
Florianópolis
Hospital Sao Lucas- Faculdade de Medicina da PUCRS
Porto Alegre
Clínica AMO
Salvador
Nucleo de Oncologia da Bahia
Salvador
Faculdade de Medicina do ABC
Santo André
Hosital Alemão Oswaldo Cruz
São Paulo
Hospital A C Camargo/ Fundação Antonio Prudente
São Paulo
Hospital das Clínicas - FMUSP
São Paulo
Instituto Arnaldo Vieira de Carvalho - IAVC
São Paulo
UNIFESP
São Paulo
About this study
Official title: 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.
Read the 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.
- Conditions
- Chemotherapy-induced Diarrhea
- Being tested
- Octreotide Long Acting Release, Standard Treatment
- Keywords
- Colorectal cancer, diarrhea, drug therapy, octreotide, fluorouracil, irinotecan, capecitabine, prevention
- Medical subject headings
- Colorectal Neoplasms, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Octreotide Long Acting ReleaseDrug
Also called Octreotide LAR, Sandostatin LAR
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.
Standard TreatmentOther
Physician treatment of choice for chemotherapy induced diarrhea other than Octreotide LAR.
| Study group | Role | What they receive |
|---|---|---|
| Octreotide Long Acting Release | Experimental | Prevention of Chemotherapy Induced Diarrhea (CID) Receives: Drug: Octreotide Long Acting Release |
| Standard Treatment | Other | Physician treatment of choice for chemotherapy induced diarrhea other than Octreotide LAR. Receives: Other: Standard Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 month overall
Secondary outcomes (10)
Number of Episodes of Diarrhea by Patient
Number of episodes of diarrhea is evaluated by patient diaries recorded on a daily basis.
Measured: 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.)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 6 months overall
Percentage of Participants Who Need Opioids for Control of Diarrhea
Measured: 6 months overall
Percentage of Patients Hospitalized Due to Diarrhea
Measured: 6 months overall
Percentage of Participants Who Need Intravenous Hydration for Control of Diarrhea
Measured: 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.
Measured: 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.
Measured: Baseline to Day 168
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2007 (estimated)
- Study startApr 2008
- Primary completionSep 2010
- Study completionSep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chemotherapy-induced DiarrheaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 139 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00582426
- Sponsor's protocol ID
- CSMS995AIC04
- Acronym
- LARCID
- Status last verified
- Apr 2015
- First submitted
- 21 Dec 2007
- Last updated
- 4 May 2015
- Results posted
- Yes, on ClinicalTrials.gov
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.
PubMed 24516038
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LARCID: Evaluation of Octreotide LAR in Prevention of Chemotherapy-induced Diarrhea
- ClinicalTrials.gov ID
- NCT00582426
- Acronym / sponsor ID
- LARCID / CSMS995AIC04
- Conditions
- Chemotherapy-induced Diarrhea
- Keywords
- Colorectal cancer, diarrhea, drug therapy, octreotide, fluorouracil, irinotecan, capecitabine, prevention
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 139 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Apr 2008
- Primary completion
- Sep 2010 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 28 Dec 2007 (estimated)
- Results
- Posted 27 Mar 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Octreotide Long Acting Release | Experimental | Drug: Octreotide Long Acting ReleasePrevention of Chemotherapy Induced Diarrhea (CID) |
| Standard Treatment | Other | Other: Standard TreatmentPhysician treatment of choice for chemotherapy induced diarrhea other than Octreotide LAR. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (16 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Octreotide Long Acting ReleaseAlso: Octreotide LAR, Sandostatin LARPatients 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. | Drug | Octreotide Long Acting Release |
| Standard TreatmentPhysician treatment of choice for chemotherapy induced diarrhea other than Octreotide LAR. | Other | Standard Treatment |
Primary outcome
Percentage of Participants Developing Diarrhea (Grade 1 to 4)
Time frame: 6 month overall
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.
10 secondary outcomes
Number of Episodes of Diarrhea by Patient
Time frame: 6 months overall
Number of Episodes of Diarrhea by Patient by Cycle
Time frame: at each cycle (28 days per cycle)
Percentage of Patients by Grade of Diarrhea
Time frame: 6 months overall
Percentage of Episodes by Grade
Time frame: 6 months overall
Percentage of Participants Who Need Chemotherapy Dose Reduction Due to Diarrhea
Time frame: 6 months overall
Percentage of Participants Who Need Opioids for Control of Diarrhea
Time frame: 6 months overall
Percentage of Patients Hospitalized Due to Diarrhea
Time frame: 6 months overall
Percentage of Participants Who Need Intravenous Hydration for Control of Diarrhea
Time frame: 6 months overall
Percentage of Participants With Complete or Partial Response at Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: 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)
Time frame: Baseline to Day 168
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24516038Hoff 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Octreotide Long Acting Release and Standard Treatment in people with Chemotherapy-induced Diarrhea, run by Novartis Pharmaceuticals at 11 sites in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Mar 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Developing Diarrhea (Grade 1 to 4) (time frame: 6 month overall). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00582426, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2015.