Metastatic Colorectal CancerPhase 2FOLFIRI-ADNCT01639326
Study to Evaluate the Efficacy and Safety of FOLFIRI-AD in Patients With Metastatic Colorectal Cancer UGT1A Genotype 1
A Phase 2 study testing Irinotecan high doses and Irinotecan standard doses in people with Metastatic Colorectal Cancer, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 3 sites in Spain.
Trial summary
This study aims to use the corresponding pharmacogenetic analysis to increase the dose of irinotecan in the schemes commonly used standard chemotherapy in advanced colorectal cancer treatment first. The project aims to improve the therapeutic index of chemotherapy. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Irinotecan high doses and Irinotecan standard doses
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 3 sitesSpain
- Study dates
- Jul 2012to Sep 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed metastatic colorectal adenocarcinoma not curable surgically.
- Not received prior systemic therapy for metastatic colorectal cancer. It allows receiving neoadjuvant or adjuvant chemotherapy (without irinotecan) as a treatment of the primary tumor at least six months before inclusion. All toxicities secondary to previous treatment should have been resolved before inclusion. The progression of disease (metastatic disease) should be confirmed radiologically after adjuvant treatment.
- Genotype of the gene UGT1A1 * 1 / * 1 or * 1 / * 28
- Age> or = 18 and <75 years.
- ECOG 0-1.
- Measurable disease according to RECIST version 1.1
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- Life expectancy> or equal to 3 months.
- Informed consent, dated and signed.
- Adequate bone marrow function as:
- Hemoglobin ≥ 9.0 g / dl (patients with hemoglobin <9 g / dl may be transfused before inclusion in the study) Platelet count ≥ 100 x 109 / L Absolute neutrophil count (ANC) ≥ 1.5x 109 / L - Adequate liver function as: Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN in the absence of liver metastases and ALT and AST ≤ 5 × ULN in the presence of liver metastases Alkaline phosphatase ≤ 2.5 x ULN or ≤ 5 x ULN in the presence of liver metastases or ≤ 10 x ULN in the presence of bone metastases
- Adequate renal function with creatinine levels <1.5 mg / dL. BUN> 50 ml / min
Who cannot join
- Genotype of the gene UGT1A1 * 28 / * 28 (Gilbert's syndrome)
- Patients who are pregnant or breast-feeding
- Concomitant treatment with other antineoplastic therapy other than specified.
- Patients with active infectious processes and patients with immunosuppressive therapy, or chronic anticoagulant therapy.
- History of malignancy in the last five years except basal cell carcinoma of the skin or carcinoma in situ of the cervix treated properly.
- Patients with positive serology for HIV previously known, chronic diarrhea, inflammatory bowel disease or malabsorption syndrome or tumor obstruction unresolved.
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- Clinically significant cardiovascular disease: cerebrovascular accident / stroke (≤ 6 months before inclusion in the trial), myocardial infarction (≤ 6 months before inclusion in the trial), unstable angina, uncontrolled hypertension, congestive heart failure grade II or higher NYHA or serious cardiac arrhythmia.
- Patients with significant neurological or psychiatric disorders, including dementia or poorly controlled epilepsy.
- Patients with any contraindications specified in the Summary of study drug.
Trial locations and contacts
3 sites in 1 country.
Spain3 sites, 3 recruiting
- Recruiting
Hospital de la Santa Creu i Sant Pau
Barcelona, Barcelona, 08025
David Páez, MD, DPaez@santpau.cat
David Paez, MD
- Recruiting
Hospital de Mataró
Mataró, Catalunya/Barcelona
Pilar Lines, MD
Pilar Lines, MD
- Recruiting
Hospital Universitari Mutua de Terrassa
Terrassa, Catalunya/Barcelona, 08221
Julen Fernandez, MD
J. Fernandez, MD
About this study
Official title: Phase II Randomized Pharmacogenetic Study to Evaluate the Efficacy and Safety of FOLFIRI Schedule With High Doses of Irinotecan (FOLFIRI-AD) in Patients With Metastatic Colorectal Cancer According to UGT1A Genotype 1.
This study aims to use the corresponding pharmacogenetic analysis to increase the dose of irinotecan in the schemes commonly used standard chemotherapy in advanced colorectal cancer treatment first. The project aims to improve the therapeutic index of chemotherapy. This optimization is raised based on the administration of different doses of the drug depending on the genotype UGT1A1 gene. The research team proposes this project to demonstrate how the administration of high doses of irinotecan in the FOLFIRI scheme in patients with genotype UGT1A1 favorable (wild homozygous * 1 / * 1 and heterozygous * 1 / * 28), significantly improves the efficiency of the antineoplastic agent without significant increase in toxicity. Secondarily will assess the possible prognostic factors related to tolerance and efficacy.
The primary objective is to evaluate the efficacy of high doses of irinotecan in the FOLFIRI scheme in patients with metastatic colorectal cancer with a favorable genotype UGT1A1 (wild homozygous * 1 / * 1 and heterozygous * 1 / * 28).
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Irinotecan high doses, Irinotecan standard doses
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Irinotecan high dosesDrug
Irinotecan dose of 300 mg / m² in patients UGT1A1 * 1 / * 1 and 260 mg / m² in patients UGT1A1 * 1 / * 28 intravenous infusion over 90 minutes and folinic acid at a dose of 400 mg / m² intravenous infusion over 2 hours and 5-FU at a dose of 400 mg / m² intravenous bolus and 5-FU 2400 mg / m² intravenous infusion for 46 hours.
Irinotecan standard dosesDrug
Irinotecan at a dose of 180 mg / m² intravenous infusion over 90 minutes and folinic acid at a dose of 400 mg / m intravenous infusion over 2 hours and 5-FU at a dose of 400 mg / m² intravenous bolus and 5-FU 2400 mg / m² intravenous infusion for 46 hours.
| Study group | Role | What they receive |
|---|---|---|
| Irinotecan high doses | Experimental | Patients will receive irinotecan dose of 300 mg / m² in patients UGT1A1 * 1 / * 1 and 260 mg / m² in patients UGT1A1 * 1 / * 28 intravenous infusion over 90 minutes and folinic acid at a dose of 400 mg / m² intravenous infusion over 2 hours and 5-FU at a dose of 400 mg / m² intravenous bolus and 5-FU 2400 mg / m² intravenous infusion for 46 hours. Receives: Drug: Irinotecan high doses |
| Irinotecan standard doses | Active comparator | Patients will receive irinotecan at a dose of 180 mg / m² intravenous infusion over 90 minutes and folinic acid at a dose of 400 mg / m intravenous infusion over 2 hours and 5-FU at a dose of 400 mg / m² intravenous bolus and 5-FU 2400 mg / m² intravenous infusion for 46 hours Receives: Drug: Irinotecan standard doses |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall objective response rate (RR) by RECIST criteria v1.1
The objective response rate, defined as the percentage of subjects who achieved a complete response (CR) or partial (PR) response will be evaluated according to RECIST criteria version 1.1
Measured: 24 months
Secondary outcomes (4)
Adverse Events
The intensity of the adverse reactions are classified according to the system Toxicity Criteria NCI v 4.0.
Measured: 24 months
Progression free survival
Elapsed time from inclusion to the date of documented disease progression or death from any cause (whichever occurs first).
Measured: 24 months
Overall survival
Elapsed time from inclusion to the time when death occurs from any cause. The subjects lost to follow up will be censored at the date of last follow up.
Measured: 24 months
overall response duration
be measured from the date of the first documentation of RP or RC (whatever the state to register first) until the first date to register progression (PG) or death from any cause. Only in this analysis included subjects who achieved a CR or PR.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2012 (estimated)
- Study startJul 2012
- Primary completionJul 2018 (estimated)
- Study completionSep 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Páez, MD, Principal investigator, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauMontserrat Baiget, MD, Study chair, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01639326
- Sponsor's protocol ID
- IIBSP-IRI-2011-134
- Acronym
- FOLFIRI-AD
- Status last verified
- Jun 2012
- First submitted
- 10 Jul 2012
- Last updated
- 7 May 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomized Pharmacogenetic Study to Evaluate the Efficacy and Safety of FOLFIRI Schedule With High Doses of Irinotecan (FOLFIRI-AD) in Patients With Metastatic Colorectal Cancer According to UGT1A Genotype 1.
- ClinicalTrials.gov ID
- NCT01639326
- Acronym / sponsor ID
- FOLFIRI-AD / IIBSP-IRI-2011-134
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Jul 2018 (estimated)
- Study completion
- Sep 2018 (estimated)
- First posted
- 12 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to use the corresponding pharmacogenetic analysis to increase the dose of irinotecan in the schemes commonly used standard chemotherapy in advanced colorectal cancer treatment first. The project aims to improve the therapeutic index of chemotherapy. This optimization is raised based on the administration of different doses of the drug depending on the genotype UGT1A1 gene. The research team proposes this project to demonstrate how the administration of high doses of irinotecan in the FOLFIRI scheme in patients with genotype UGT1A1 favorable (wild homozygous * 1 / * 1 and heterozygous * 1 / * 28), significantly improves the efficiency of the antineoplastic agent without significant increase in toxicity. Secondarily will assess the possible prognostic factors related to tolerance and efficacy.
The primary objective is to evaluate the efficacy of high doses of irinotecan in the FOLFIRI scheme in patients with metastatic colorectal cancer with a favorable genotype UGT1A1 (wild homozygous * 1 / * 1 and heterozygous * 1 / * 28).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Irinotecan high doses | Experimental | Drug: Irinotecan high dosesPatients will receive irinotecan dose of 300 mg / m² in patients UGT1A1 * 1 / * 1 and 260 mg / m² in patients UGT1A1 * 1 / * 28 intravenous infusion over 90 minutes and folinic acid at a dose of 400 mg / m² intravenous infusion over 2 hours and 5-FU at a dose of 400 mg / m² intravenous bolus and 5-FU 2400 mg / m² intravenous infusion for 46 hours. |
| Irinotecan standard doses | Active comparator | Drug: Irinotecan standard dosesPatients will receive irinotecan at a dose of 180 mg / m² intravenous infusion over 90 minutes and folinic acid at a dose of 400 mg / m intravenous infusion over 2 hours and 5-FU at a dose of 400 mg / m² intravenous bolus and 5-FU 2400 mg / m² intravenous infusion for 46 hours |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically confirmed metastatic colorectal adenocarcinoma not curable surgically.
- Not received prior systemic therapy for metastatic colorectal cancer. It allows receiving neoadjuvant or adjuvant chemotherapy (without irinotecan) as a treatment of the primary tumor at least six months before inclusion. All toxicities secondary to previous treatment should have been resolved before inclusion. The progression of disease (metastatic disease) should be confirmed radiologically after adjuvant treatment.
- Genotype of the gene UGT1A1 * 1 / * 1 or * 1 / * 28
- Age> or = 18 and <75 years.
- ECOG 0-1.
Key exclusion criteria (9 listed)
- Genotype of the gene UGT1A1 * 28 / * 28 (Gilbert's syndrome)
- Patients who are pregnant or breast-feeding
- Concomitant treatment with other antineoplastic therapy other than specified.
- Patients with active infectious processes and patients with immunosuppressive therapy, or chronic anticoagulant therapy.
- History of malignancy in the last five years except basal cell carcinoma of the skin or carcinoma in situ of the cervix treated properly.
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 |
|---|---|---|
| Irinotecan high dosesIrinotecan dose of 300 mg / m² in patients UGT1A1 * 1 / * 1 and 260 mg / m² in patients UGT1A1 * 1 / * 28 intravenous infusion over 90 minutes and folinic acid at a dose of 400 mg / m² intravenous infusion over 2 hours and 5-FU at a dose of 400 mg / m² intravenous bolus and 5-FU 2400 mg / m² intravenous infusion for 46 hours. | Drug | Irinotecan high doses |
| Irinotecan standard dosesIrinotecan at a dose of 180 mg / m² intravenous infusion over 90 minutes and folinic acid at a dose of 400 mg / m intravenous infusion over 2 hours and 5-FU at a dose of 400 mg / m² intravenous bolus and 5-FU 2400 mg / m² intravenous infusion for 46 hours. | Drug | Irinotecan standard doses |
Primary outcome
Overall objective response rate (RR) by RECIST criteria v1.1
Time frame: 24 months
The objective response rate, defined as the percentage of subjects who achieved a complete response (CR) or partial (PR) response will be evaluated according to RECIST criteria version 1.1
4 secondary outcomes
Adverse Events
Time frame: 24 months
Progression free survival
Time frame: 24 months
Overall survival
Time frame: 24 months
overall response duration
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2015.
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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.
David Páez, MD principal investigator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Montserrat Baiget, MD study chair
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Irinotecan high doses and Irinotecan standard doses in people with Metastatic Colorectal Cancer, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 3 sites in Spain.
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 11 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 7 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 3 sites in Spain. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Montserrat Baiget, MD (+34 93 553 56 37, MBaiget@santpau.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall objective response rate (RR) by RECIST criteria v1.1 (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 May 2015.