Colorectal CancerPhase 3IRIMADNCT06501482
Adjuvant FOLFIRI Based-chemotherapy After Resection of CLM Responding to Preoperative FOLFIRI
A Phase 3 study testing Postoperative reintroduction of FOLFIRI based chemotherapy in people with Colorectal Cancer and Colorectal Liver Metastases, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Eligible patients are patients with contraindication to preoperative oxaliplatin based-chemotherapy who underwent resection of no more than 10 colorectal liver metastases after preoperative FOLFIRI based chemotherapy with or without targeted agents. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Colorectal Liver Metastases
- What is being tested?
- Postoperative reintroduction of FOLFIRI based chemotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 254 participants
- Where
- 1 siteFrance
- Study dates
- 27 Jun 2025to 27 Jun 2031
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven resected metachronous CLM with curative intent that could not be treated with perioperative oxaliplatin-based chemotherapy for oncologic or tolerability reasons. For this study, metachronous CLM is defined as liver recurrence occurring more than 12 months after treatment of the primary colorectal cancer.
- No more than 10 treated CLM at surgery
- At least 2 cycles and no more than 8 cycles of preoperative FOLFIRI based chemotherapy ± targeted therapy.
- Preoperative FOLFIRI based chemotherapy ± targeted therapy administered no more than 12 weeks before surgery
- R0/R1resection ± radiofrequency ablation with curative intent of all liver deposits with no macroscopic residual liver disease
- Objective response to preoperative therapy defined as complete or partial radiological response and/or major or complete pathologic response or stable desease
Show all 12Show fewer
- No extrahepatic or residual liver disease on baseline work-up including thoraco-abdominal CT scan within 6 weeks after surgery. 1 non-specific lung nodule of less than 10 mm in maximum diameter is not considered as extra-hepatic metastases
- Primary tumor (or liver metastasis) of CRC must be characterized for RAS and BRAF status
- No contraindication to FOLFIRI based chemotherapy
- Patients must be 18 years old or older
- A WHO performance status of 0 or 1
- Participants must be affiliated to a social security scheme
Who cannot join
- Palliative/R2 resection of CLM
- 10 lesions or more treated at the time of surgery
- Patients undergoing only radiofrequency ablation of all liver deposit (this situation precludes the assessment of pathologic response to preoperative chemotherapy)
- Extra-hepatic or residual metastasis of CRC
- Absence of objective response to therapy (radiological or pathological response )
- Inflammatory bowel disease
Show all 11Show fewer
- Known UGT1A1*28 allele homozygosity
- complete absence of dihydropyrimidine dehydrogenase (DPD) activity (blood uracil level ≥ 150 ng/ml
- Contraindications to investigational medicinal products (irinotecan, 5-FU, folinic acid) and to auxiliary medicinal products (ondansetron, methylprednisolone)
- Persistent toxicity ≥ grade 1 related to preoperative FOLFIRI based chemotherapy
- Known pregnancy (pregnancy test for women of childbearing) or breastfeeding women
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Hôpital Kremlin Bicêtre
Paris, Île-de-France Region, 75010
stéphane BENOIST, MHD, PHD, +33 1 45 21 34 72, Stephane.benoist@aphp.fr
Antoine BROUQUET, +33 1 45 21 34 70, Anoine.brouquet@aphp.fr
About this study
Official title: "Interest of Postoperative Reintroduction of Chemotherapy in Patients Undergoing Resection of Colorectal Liver Metastases After Good Response to FOLFIRI-based Chemotherapy With or Without Targeted Agent" (Intergroup FRENCH- PRODIGE)
Eligible patients are patients with contraindication to preoperative oxaliplatin based-chemotherapy who underwent resection of no more than 10 colorectal liver metastases after preoperative FOLFIRI based chemotherapy with or without targeted agents. These patients must have objective response to treatment (radiologic or pathologic response). The standard care for these patients is no postoperative treatment although benefit of reintroduction of FOLFIRI chemotherapy in good responders could be expected.
This study is a National, multicenter, open-label randomized, 2-arm, phase III superiority trial comparing postoperative reintroduction of FOLFIRI based-chemotherapy (experimental arm) vs no treatment (control arm) in patients undergoing resection of colorectal liver metastases after good response to FOLFIRI-based chemotherapy with or without targeted agent.
The primary endpoint of the study is 3-year disease free survival. Based on published data, 3-year DFS in control group (absence of postoperative treatment is 25%. Expected 3-year DFS in the experimental group is 40%. The study will randomize 254 patients (127 in the chemotherapy group and 127 in the no treatment group) in 30 french academic centers.
Read the detailed description
This study is a National, multicenter, open-label randomized, 2-arm, phase III superiority trial comparing postoperative reintroduction of FOLFIRI based-chemotherapy (experimental arm) vs no treatment (control arm) in patients undergoing resection of colorectal liver metastases after good response to FOLFIRI-based chemotherapy with or without targeted agent.
Inclusion criteria are:
- Histologically proven resected metachronous CLM with curative intent that could not be treated with perioperative oxaliplatin-based chemotherapy for oncologic or tolerability reasons. For this study, metachronous CLM is defined as liver recurrence occurring more than 12 months after treatment of the primary colorectal cancer.
- No more than 10 treated CLM at surgery
- At least 2 cycles and no more than 8 cycles of preoperative FOLFIRI based chemotherapy ± targeted therapy.
- Preoperative FOLFIRI based chemotherapy ± targeted therapy administered no more than 12 weeks before surgery
- R0/R1resection ± radiofrequency ablation with curative intent of all liver deposits with no macroscopic residual liver disease
- Objective response to preoperative therapy defined as complete or partial radiological response and/or major or complete pathologic response
- No extrahepatic or residual liver disease on baseline work-up including thoraco-abdominal CT scan within 6 weeks after surgery. 1 non-specific lung nodule of less than 10 mm in maximum diameter is not considered as extra-hepatic metastases
- Primary tumor (or liver metastasis) of CRC must be characterized for RAS and BRAF status
- No contraindication to FOLFIRI based chemotherapy
- Patients must be 18 years old or older
- A WHO performance status of 0 or 1
- Participants must be affiliated to a social security scheme The primary objective is demonstrate an improvement of disease-free survival rate at 3 years.
In the experimental arm, patients will be treated with irinotecan 180 mg/m2 + leucovorin 400 mg/m2 at day 1 then 5-FU 400 mg/m2 bolus followed by 2400 mg/m2 continuous infusion over 46 h biweekly. For a total of 12 cycles of perioperative chemotherapy including the preoperative chemotherapy.
In the control arm, patients do not receive any adjuvant treatment. This is an intention-to-treat trial. Based on published data, 3-year DFS in the control arm is 25%. Expected 3-year DFS in the experimental group is 40%. The sample size in each group is 127, with a total number of 185 events required, an exponential maximum likelihood test of equality of survival curves with a 0,050 two-sided significance level will have 80% power to detect the difference between groups (constant hazard-ratio of 0,662); assuming a 36 month length of accrual period, a 72 maximum length of follow up and 5% annual attrition (following exponential model) over study period (following exponential model) over study period.
- Conditions
- Colorectal Cancer, Colorectal Liver Metastases
- Being tested
- Postoperative reintroduction of FOLFIRI based chemotherapy
- Keywords
- Resected colorectal liver metastases, Response to preoperative chemotherapy, Postoperative FOLFIRI based chemotherapy, Disease-free survival
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Postoperative reintroduction of FOLFIRI based chemotherapyDrug
Postoperative reintroduction of FOLFIRI: irinotecan 180 mg/m2 + leucovorin 400 mg/m2 at day 1 then 5-FU 400 mg/m2 bolus followed by 2400 mg/m2 continuous infusion over 46 h biweekly. For a total of 12 cycles of perioperative chemotherapy including the preoperative chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| Postoperative FOLFIRI group | Experimental | Irinotecan 180 mg/m2 + leucovorin 400 mg/m2 at day 1 then 5-FU 400 mg/m2 bolus followed by 2400 mg/m2 continuous infusion over 46 h biweekly. For a total of 12 cycles of perioperative chemotherapy including the preoperative chemotherapy Receives: Drug: Postoperative reintroduction of FOLFIRI based chemotherapy |
| No treatment group (control group) | No intervention | No treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
The disease-free survival rate
Disease-free survival rate at 3 years defined as the proportion of surviving patients without disease recurrence measured by Kaplan-Meier in the two treatment arms from the time to randomization. Disease-free survival will be defined as follows: time between randomization and disease recurrence or death whichever occurs first.
In this trial, the disease-free survival is defined as the time to occurrence of first recurrence or death whatever comes first.
Diagnosis of recurrence can be made only when the clinical and laboratory findings meet at least one of the criteria defined below:
- Objective radiological recurrence on radiological imaging (ultrasound, CT scan, MRI scan, TEP scan as indicated by the clinical picture)
- Positive cytology or biopsy (in case of ascites, anastomotic recurrence, doubt on radiological imaging) Note: an isolated elevated tumor marker level will not be considered acceptable evidence of cancer recurrence.
- Death.
Measured: 3 years
Secondary outcomes (2)
The overall survival rate
All patients will be followed-up for at least 3 year after randomization or until death. Overall survival is defined as survival duration from the time of randomization to death. Patients who are still alive when last traced will be censored at the date of last follow-up.
Measured: 3 years
The Liver-free survival rate
Liver-free survival is defined as survival duration from the time of randomization to first liver recurrence.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2024
- Study start27 Jun 2025
- Primary completion27 Jun 2028 (estimated)
- Study completion27 Jun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- National, multicenter, open-label randomized, 2-arm, phase III superiority trial
- Masking
- None (open label)
- Enrolment
- 254 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Eric VICAUT, MHD, PHD, Study chair, APHPEric VICAUT, MHD, PHD, Principal investigator, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06501482
- Sponsor's protocol ID
- 220917
- Other IDs
- 2023-504831-42-00, 2023
- Acronym
- IRIMAD
- Status last verified
- Sep 2026
- First submitted
- 27 Jun 2024
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Labiad C, Brouquet A, Bachet JB, Abdalla S, Lefevre J, Vicaut E, Benoist S; on behalf the FRENCH study group. Postoperative chemotherapy reintroduction in good responders after colorectal liver metastases resection: A French randomized phase III trial - IRIMAD. Dig Liver Dis. 2026 Oct 8:S1590-8658(26)00967-9. doi: 10.1016/j.dld.2026.09.014. Online ahead of print.
PubMed 42850173
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "Interest of Postoperative Reintroduction of Chemotherapy in Patients Undergoing Resection of Colorectal Liver Metastases After Good Response to FOLFIRI-based Chemotherapy With or Without Targeted Agent" (Intergroup FRENCH- PRODIGE)
- ClinicalTrials.gov ID
- NCT06501482
- Acronym / sponsor ID
- IRIMAD / 220917
- Conditions
- Colorectal Cancer, Colorectal Liver Metastases
- Keywords
- Resected colorectal liver metastases, Response to preoperative chemotherapy, Postoperative FOLFIRI based chemotherapy, Disease-free survival
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 254 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 27 Jun 2025 (actual)
- Primary completion
- 27 Jun 2028 (estimated)
- Study completion
- 27 Jun 2031 (estimated)
- First posted
- 15 Jul 2024 (actual)
- 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.
Eligible patients are patients with contraindication to preoperative oxaliplatin based-chemotherapy who underwent resection of no more than 10 colorectal liver metastases after preoperative FOLFIRI based chemotherapy with or without targeted agents. These patients must have objective response to treatment (radiologic or pathologic response). The standard care for these patients is no postoperative treatment although benefit of reintroduction of FOLFIRI chemotherapy in good responders could be expected.
This study is a National, multicenter, open-label randomized, 2-arm, phase III superiority trial comparing postoperative reintroduction of FOLFIRI based-chemotherapy (experimental arm) vs no treatment (control arm) in patients undergoing resection of colorectal liver metastases after good response to FOLFIRI-based chemotherapy with or without targeted agent.
The primary endpoint of the study is 3-year disease free survival. Based on published data, 3-year DFS in control group (absence of postoperative treatment is 25%. Expected 3-year DFS in the experimental group is 40%. The study will randomize 254 patients (127 in the chemotherapy group and 127 in the no treatment group) in 30 french academic centers.
Detailed description
This study is a National, multicenter, open-label randomized, 2-arm, phase III superiority trial comparing postoperative reintroduction of FOLFIRI based-chemotherapy (experimental arm) vs no treatment (control arm) in patients undergoing resection of colorectal liver metastases after good response to FOLFIRI-based chemotherapy with or without targeted agent.
Inclusion criteria are:
- Histologically proven resected metachronous CLM with curative intent that could not be treated with perioperative oxaliplatin-based chemotherapy for oncologic or tolerability reasons. For this study, metachronous CLM is defined as liver recurrence occurring more than 12 months after treatment of the primary colorectal cancer.
- No more than 10 treated CLM at surgery
- At least 2 cycles and no more than 8 cycles of preoperative FOLFIRI based chemotherapy ± targeted therapy.
- Preoperative FOLFIRI based chemotherapy ± targeted therapy administered no more than 12 weeks before surgery
- R0/R1resection ± radiofrequency ablation with curative intent of all liver deposits with no macroscopic residual liver disease
- Objective response to preoperative therapy defined as complete or partial radiological response and/or major or complete pathologic response
- No extrahepatic or residual liver disease on baseline work-up including thoraco-abdominal CT scan within 6 weeks after surgery. 1 non-specific lung nodule of less than 10 mm in maximum diameter is not considered as extra-hepatic metastases
- Primary tumor (or liver metastasis) of CRC must be characterized for RAS and BRAF status
- No contraindication to FOLFIRI based chemotherapy
- Patients must be 18 years old or older
- A WHO performance status of 0 or 1
- Participants must be affiliated to a social security scheme The primary objective is demonstrate an improvement of disease-free survival rate at 3 years.
In the experimental arm, patients will be treated with irinotecan 180 mg/m2 + leucovorin 400 mg/m2 at day 1 then 5-FU 400 mg/m2 bolus followed by 2400 mg/m2 continuous infusion over 46 h biweekly. For a total of 12 cycles of perioperative chemotherapy including the preoperative chemotherapy.
In the control arm, patients do not receive any adjuvant treatment. This is an intention-to-treat trial. Based on published data, 3-year DFS in the control arm is 25%. Expected 3-year DFS in the experimental group is 40%. The sample size in each group is 127, with a total number of 185 events required, an exponential maximum likelihood test of equality of survival curves with a 0,050 two-sided significance level will have 80% power to detect the difference between groups (constant hazard-ratio of 0,662); assuming a 36 month length of accrual period, a 72 maximum length of follow up and 5% annual attrition (following exponential model) over study period (following exponential model) over study period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- National, multicenter, open-label randomized, 2-arm, phase III superiority trial
| Arm | Type | Receives |
|---|---|---|
| Postoperative FOLFIRI group | Experimental | Drug: Postoperative reintroduction of FOLFIRI based chemotherapyIrinotecan 180 mg/m2 + leucovorin 400 mg/m2 at day 1 then 5-FU 400 mg/m2 bolus followed by 2400 mg/m2 continuous infusion over 46 h biweekly. For a total of 12 cycles of perioperative chemotherapy including the preoperative chemotherapy |
| No treatment group (control group) | No intervention | –No treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically proven resected metachronous CLM with curative intent that could not be treated with perioperative oxaliplatin-based chemotherapy for oncologic or tolerability reasons. For this study, metachronous CLM is defined as liver recurrence occurring more than 12 months after treatment of the primary colorectal cancer.
- No more than 10 treated CLM at surgery
- At least 2 cycles and no more than 8 cycles of preoperative FOLFIRI based chemotherapy ± targeted therapy.
- Preoperative FOLFIRI based chemotherapy ± targeted therapy administered no more than 12 weeks before surgery
- R0/R1resection ± radiofrequency ablation with curative intent of all liver deposits with no macroscopic residual liver disease
Key exclusion criteria (11 listed)
- Palliative/R2 resection of CLM
- 10 lesions or more treated at the time of surgery
- Patients undergoing only radiofrequency ablation of all liver deposit (this situation precludes the assessment of pathologic response to preoperative chemotherapy)
- Extra-hepatic or residual metastasis of CRC
- Absence of objective response to therapy (radiological or pathological response )
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 |
|---|---|---|
| Postoperative reintroduction of FOLFIRI based chemotherapyPostoperative reintroduction of FOLFIRI: irinotecan 180 mg/m2 + leucovorin 400 mg/m2 at day 1 then 5-FU 400 mg/m2 bolus followed by 2400 mg/m2 continuous infusion over 46 h biweekly. For a total of 12 cycles of perioperative chemotherapy including the preoperative chemotherapy | Drug | Postoperative FOLFIRI group |
Primary outcome
The disease-free survival rate
Time frame: 3 years
Disease-free survival rate at 3 years defined as the proportion of surviving patients without disease recurrence measured by Kaplan-Meier in the two treatment arms from the time to randomization. Disease-free survival will be defined as follows: time between randomization and disease recurrence or death whichever occurs first. In this trial, the disease-free survival is defined as the time to occurrence of first recurrence or death whatever comes first. Diagnosis of recurrence can be made only when the clinical and laboratory findings meet at least one of the criteria defined below: * Objective radiological recurrence on radiological imaging (ultrasound, CT scan, MRI scan, TEP scan as indicated by the clinical picture) * Positive cytology or biopsy (in case of ascites, anastomotic recurrence, doubt on radiological imaging) Note: an isolated elevated tumor marker level will not be considered acceptable evidence of cancer recurrence. * Death.
2 secondary outcomes
The overall survival rate
Time frame: 3 years
The Liver-free survival rate
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2026.
- Derived from this study: PubMed 42850173Labiad C, Brouquet A, Bachet JB, Abdalla S, Lefevre J, Vicaut E, Benoist S; on behalf the FRENCH study group. Postoperative chemotherapy reintroduction in good responders after colorectal liver metastases resection: A French randomized phase III trial - IRIMAD. Dig Liver Dis. 2026 Oct 8:S1590-8658(26)00967-9. doi: 10.1016/j.dld.2026.09.014. Online ahead of print.
- Individual participant dataSharing planned: No
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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.
Eric VICAUT, MHD, PHD study chair
APHP
Eric VICAUT, MHD, PHD principal investigator
APHP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Postoperative reintroduction of FOLFIRI based chemotherapy in people with Colorectal Cancer and Colorectal Liver Metastases, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 12 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Stéphane BENOIST, MHD, PHD (33 1 45 21 34 72, Stephane.benoist@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The disease-free survival rate (time frame: 3 years). 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 NCT06501482, 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 9 Sep 2026.