Colorectal Cancer MetastaticPhase 2SULTANNCT03164655
Improving SUrgery of Liver Metastases: a Trial of the Arterial Chemotherapy Network
A Phase 2 study testing Oxaliplatin, Cetuximab, Bevacizumab, Panitumumab, Irinotecan, Leucovorin, 5-Fluorouracil in people with Colorectal Cancer Metastatic, run by UNICANCER at 4 sites in France.
Trial summary
National trial, multicenter, randomized, phase II comparing treatment intensification with hepatic arterial infusion chemotherapy plus systemic chemotherapy (CT) to systemic chemotherapy alone in patients with liver-only colorectal metastases (CRLM) considered still non resectable after at least two months of systemic… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer Metastatic
- What is being tested?
- Oxaliplatin, Cetuximab, Bevacizumab, Panitumumab, Irinotecan, Leucovorin, 5-Fluorouracil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 4 sitesFrance
- Study dates
- 25 Jul 2018to 15 Nov 2021
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed colorectal cancer (CRC), and radiologic or histologic proof of CRLM not amenable to a curative intent-treatment.
- At least two months of prior induction systemic CT with oxaliplatin and/or irinotecan combined with a fluoropyrimidine combined or not to a targeted therapy (e.g., anti-EGFR or antiangiogenic antibody) for metastatic disease (patients ending their adjuvant chemotherapy after primary tumor resection since more than 6 months should also have received first-line chemotherapy for metastatic disease). Further systemic chemotherapy lines are allowed.
- Unresectability of the CRLM will be confirmed by a centralized multidisciplinary expert panel (composed of surgeons, radiologists, interventional radiologists and medical oncologists). The panel will review the CT scan and MRI of the patients (weekly web conference). Non-resectability criteria (one of the following criteria):
- Upfront R0/R1 resection of all CRLM (that leaves at least two adequately perfused and drained segments) is not possible
- and/or metastases in contact with major vessels of the remnant liver which would require resection of the vessel for an R0 resection (i.e., tumor involvement of main portal right and left portal veins, of the three main hepatic veins, or of the retrohepatic vena cava)
- and/or documented progressive disease on imaging (according to the RECIST v1.1) or doubling of serum levels of carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA 19-9) following ≥2 months of induction CT
Show all 17Show fewer
- At least one measurable liver metastasis according to the RECIST v1.1
- Age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Normal liver function, i.e. bilirubin <1.5 times the upper limit of normal values (ULN), aminotransferases <5 ULN, alkaline phosphatase <5 ULN
- International normalized ratio (INR) <1.5 ULN
- Neutrophils >1500/mm³, platelets >100 000/mm³, hemoglobin >9 g/dL (transfusion allowed)
- Calculated creatinine clearance >50 mL/min (Cockcroft and Gault formula)
- Informed consent signed by the patient or his/her legal representative
- Patient affiliated to a social security regimen
- Potentially reproductive patients must agree to use an effective contraceptive method or practice adequate methods of birth control or practice complete abstinence while on treatment, and for at least 6 months after the last dose of study drug.
- Uracilemia <16 ng/ml
Who cannot join
- Patient eligible for curative-intent treatment of CRLM (i.e. resection and/or thermoablation), according to the local multidisciplinary team and/or the central review.
- Definitive anatomical contraindication to complete surgical resection (any of the following criteria):
- More than two lesions in all liver segments
- Bilobar liver metastasis and more than three lesions >3 cm in the hepatic lobe the least affected (i.e. the future remnant liver)
- Bilobar liver metastasis and disease liver extend >50%
- Extrahepatic tumor disease (except ≤3 lung nodules <10 mm deemed amenable to curative-intent resection/thermoablation and non-resected primary tumor with no or mild symptoms)
Show all 34Show fewer
- Patient with contraindication for trial drugs (investigators have to refer to drugs SmPC); contraindication limited to targeted therapy (e.g., anti-EGFR or antiangiogenic antibody) is not an exclusion criteria
- Disease progression after FOLFOXIRI/FOLFIRINOX
- Sensory neuropathy ≥ grade 2 (National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.4.0)
- If patients received bevacizumab, following non-inclusion criteria must be respected:
- Proteinuria >1 g,
- Gastro-intestinal fistulae or perforation,
- Hypersensitivity to Chinese hamster ovary cell products or other human recombinant antibody,
- Major surgery in the last 28 days.
- If patients received panitumumab, following non-inclusion criteria must be respected:
- Interstitial lung disease,
- Pulmonary fibrosis.
- Significant chronic liver disease (resulting in portal hypertension and/or liver insufficiency)
- Allergy to contrast media that cannot be managed with standard care
- Previous organ transplantation, HIV or other immunodeficiency syndromes
- Concomitant or past history of cancer within 5 years prior to entry into the trial other than adequately treated basal-cell skin cancer or in situ carcinoma of the cervix
- Patients with clinically significant active heart disease or myocardial infarction in the last 6 months
- Concomitant medications/comorbidities that may prevent the patient from receiving study treatments as uncontrolled intercurrent illness (for instance: active infection, active inflammatory disorders, inflammatory bowel disease, intestinal obstruction, uncontrolled hypertension systolic >15 and diastolic >9, symptomatic congestive heart failure…)
- Ionic disorders as:
- Kalemia ≥1 x ULN
- Magnesemia <0.5 mmol/L
- Calcemia <2 mmol/L
- Patient with a dihydropyrimidine dehydrogenase (DPD) deficiency; Uracilemia ≥16 ng/ml, the test should be done for all patients before first 5-FU administration, according to "agence nationale de sécurité du médicament" (ANSM) communication regarding recommendation about high risk of no testing DPD in patient before 5-FU administration
- QT/QTc >450 msec for men and > 470 msec for women
- Concomitant intake of St. John's wort
- Patient already included in another clinical trial with an experimental treatment
- Pregnancy or lactation
- Patients deprived of liberty or under guardianship
- Patients unable to undergo medical monitoring test for geographical, social or psychological reasons
Trial locations and contacts
4 sites in 1 country.
France4 sites
Ico Paul Papin
Angers
Centre Eugene Marquis
Rennes
Chp Saint Gregoire
Saint-Grégoire
Gustave Roussy
Villejuif, 94
About this study
Official title: A Randomized Phase II Study Comparing Treatment Intensification With CIAH Plus Systemic Chemotherapy to Systemic Chemotherapy Alone in Patients With Liver-only Colorectal Metastases Considered Still Non Resectable After at Least Two Months of Systemic Induction Chemotherapy
National trial, multicenter, randomized, phase II comparing treatment intensification with hepatic arterial infusion chemotherapy plus systemic chemotherapy (CT) to systemic chemotherapy alone in patients with liver-only colorectal metastases (CRLM) considered still non resectable after at least two months of systemic induction chemotherapy.
Read the detailed description
to compare the efficacy of CT intensification combining hepatic arterial infusion(HAI) oxaliplatin plus IV FOLFIRI plus targeted therapy (anti-epidermal growth factor receptor (EGFR) or bevacizumab) to conventional systemic CT alone plus targeted therapy (anti-EGFR or antiangiogenic antibody), in patients with liver-only CRLM not amenable to curative-intent resection (and/or ablation) after systemic induction CT in terms of conversion to complete (R0 R1) resection (or ablation) rate (CRR).
- Conditions
- Colorectal Cancer Metastatic
- Being tested
- Oxaliplatin, Cetuximab, Bevacizumab, Panitumumab, Irinotecan, Leucovorin, 5-Fluorouracil
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oxaliplatin, Cetuximab, Bevacizumab, Panitumumab, Irinotecan, Leucovorin, 5-FluorouracilDrug
Oxaliplatin 100 mg/m² infusion in 2 hours, Cetuximab 500mg/m² infusion in 2 hours, Bevacizumab 5 mg/kg infusion in 30 minutes, Panitumumab 6 mg/kg, Irinotecan 180 mg/m² over 90 minutes to begin 30 minutes after folinic acid infusion is started, Leucovorin 400 mg/m² infusion in 2 hours, 5-Fluorouracil 2400 mg/m² infusion continuous in 46h
| Study group | Role | What they receive |
|---|---|---|
| HAI oxaliplatin combined with I.V. FOLFIRI + target therapy | Experimental | * HAI oxaliplatin 100 mg/m² on D1
* I.V. cetuximab 500 mg/m² or panitumumab 6 mg/kg or bevacizumab 5 mg/kg D1 according to RAS status and prior response/tolerance to systemic induction CT
* modified FOLFIRI regimen without fluorouracil bolus
* I.V. irinotecan 180 mg/m² D1
* I.V. bolus 5-Fluorouracil (5-FU): 0
* I.V. leucovorin 400 mg/m² in 2 hours D1
* I.V. continuous infusion 5-FU 2400 mg/m² in 46 hours Receives: Drug: Oxaliplatin, Cetuximab, Bevacizumab, Panitumumab, Irinotecan, Leucovorin, 5-Fluorouracil |
| conventional systemic CT | Active comparator | * Response to systemic induction CT
* Toxicity and duration of the systemic induction CT
* RAS status
* Current guidelines/standard of care Receives: Drug: Oxaliplatin, Cetuximab, Bevacizumab, Panitumumab, Irinotecan, Leucovorin, 5-Fluorouracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Curative-intent (R0-R1) resection (and/or ablation) rate (CRR) of CRLM
Curative-intent (R0-R1) resection (and/or ablation) rate (CRR) of CRLM confirmed by a systematic review of the surgical and pathological report by an independent committee blind to the treatment received
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2017
- Study start25 Jul 2018
- Primary completion15 Jul 2021
- Study completion15 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Colorectal Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by UNICANCERThe 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNICANCER
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Valérie Boige, Principal investigator, Gustave Roussy Villejuif
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03164655
- Sponsor's protocol ID
- UCGI 30 - PRODIGE 53 SULTAN
- Other IDs
- 2016-001493-15, 2016
- Acronym
- SULTAN
- Status last verified
- Sep 2024
- First submitted
- 22 May 2017
- Last updated
- 1 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
Publications
Boileve A, Audemar F, Dupont-Bierre E, Le Sourd S, Ulusakarya A, Chauvenet M, Benmaziame A, Wagner M, Goere D, Dromain C, Gelli M, Pezzella V, Bonnet B, Tanguy ML, Boige V. Treatment Intensification with Hepatic Arterial Infusion Chemotherapy in Patients with Liver-Only Colorectal Metastases Still Unresectable After Systemic Induction Chemotherapy: Exploratory Findings From a Prematurely Closed Multicenter Randomized Phase II Study: SULTAN UCGI 30/PRODIGE 53 (NCT03164655). Ann Surg Oncol. 2026 Feb;33(2):1460-1469. doi: 10.1245/s10434-025-18570-5. Epub 2025 Oct 21.
PubMed 41118066Boileve A, Maillard A, Wagner M, Dromain C, Laurent C, Dupont Bierre E, Le Sourd S, Audemar F, Ulusakarya A, Guerin-Meyer V, Smisth D, Pezzella V, De Baere T, Goere D, Gelli M, Taieb J, Boige V. Treatment intensification with hepatic arterial infusion chemotherapy in patients with liver-only colorectal metastases still unresectable after systemic induction chemotherapy - a randomized phase II study -- SULTAN UCGI 30/PRODIGE 53 (NCT03164655)- study protocol. BMC Cancer. 2020 Jan 30;20(1):74. doi: 10.1186/s12885-020-6571-7.
PubMed 32000724
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Study Comparing Treatment Intensification With CIAH Plus Systemic Chemotherapy to Systemic Chemotherapy Alone in Patients With Liver-only Colorectal Metastases Considered Still Non Resectable After at Least Two Months of Systemic Induction Chemotherapy
- ClinicalTrials.gov ID
- NCT03164655
- Acronym / sponsor ID
- SULTAN / UCGI 30 - PRODIGE 53 SULTAN
- Conditions
- Colorectal Cancer Metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- UNICANCERUniversity, hospital or other
- Study start
- 25 Jul 2018 (actual)
- Primary completion
- 15 Jul 2021 (actual)
- Study completion
- 15 Nov 2021 (actual)
- First posted
- 23 May 2017 (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.
National trial, multicenter, randomized, phase II comparing treatment intensification with hepatic arterial infusion chemotherapy plus systemic chemotherapy (CT) to systemic chemotherapy alone in patients with liver-only colorectal metastases (CRLM) considered still non resectable after at least two months of systemic induction chemotherapy.
Detailed description
to compare the efficacy of CT intensification combining hepatic arterial infusion(HAI) oxaliplatin plus IV FOLFIRI plus targeted therapy (anti-epidermal growth factor receptor (EGFR) or bevacizumab) to conventional systemic CT alone plus targeted therapy (anti-EGFR or antiangiogenic antibody), in patients with liver-only CRLM not amenable to curative-intent resection (and/or ablation) after systemic induction CT in terms of conversion to complete (R0 R1) resection (or ablation) rate (CRR).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HAI oxaliplatin combined with I.V. FOLFIRI + target therapy | Experimental | Drug: Oxaliplatin, Cetuximab, Bevacizumab, Panitumumab, Irinotecan, Leucovorin, 5-Fluorouracil* HAI oxaliplatin 100 mg/m² on D1 * I.V. cetuximab 500 mg/m² or panitumumab 6 mg/kg or bevacizumab 5 mg/kg D1 according to RAS status and prior response/tolerance to systemic induction CT * modified FOLFIRI regimen without fluorouracil bolus * I.V. irinotecan 180 mg/m² D1 * I.V. bolus 5-Fluorouracil (5-FU): 0 * I.V. leucovorin 400 mg/m² in 2 hours D1 * I.V. continuous infusion 5-FU 2400 mg/m² in 46 hours |
| conventional systemic CT | Active comparator | Drug: Oxaliplatin, Cetuximab, Bevacizumab, Panitumumab, Irinotecan, Leucovorin, 5-Fluorouracil* Response to systemic induction CT * Toxicity and duration of the systemic induction CT * RAS status * Current guidelines/standard of care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histologically confirmed colorectal cancer (CRC), and radiologic or histologic proof of CRLM not amenable to a curative intent-treatment.
- At least two months of prior induction systemic CT with oxaliplatin and/or irinotecan combined with a fluoropyrimidine combined or not to a targeted therapy (e.g., anti-EGFR or antiangiogenic antibody) for metastatic disease (patients ending their adjuvant chemotherapy after primary tumor resection since more than 6 months should also have received first-line chemotherapy for metastatic disease). Further systemic chemotherapy lines are allowed.
- Unresectability of the CRLM will be confirmed by a centralized multidisciplinary expert panel (composed of surgeons, radiologists, interventional radiologists and medical oncologists). The panel will review the CT scan and MRI of the patients (weekly web conference). Non-resectability criteria (one of the following criteria):
- At least one measurable liver metastasis according to the RECIST v1.1
- Age ≥18 years
Key exclusion criteria (34 listed)
- Patient eligible for curative-intent treatment of CRLM (i.e. resection and/or thermoablation), according to the local multidisciplinary team and/or the central review.
- Definitive anatomical contraindication to complete surgical resection (any of the following criteria):
- Extrahepatic tumor disease (except ≤3 lung nodules <10 mm deemed amenable to curative-intent resection/thermoablation and non-resected primary tumor with no or mild symptoms)
- Patient with contraindication for trial drugs (investigators have to refer to drugs SmPC); contraindication limited to targeted therapy (e.g., anti-EGFR or antiangiogenic antibody) is not an exclusion criteria
- Disease progression after FOLFOXIRI/FOLFIRINOX
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 |
|---|---|---|
| Oxaliplatin, Cetuximab, Bevacizumab, Panitumumab, Irinotecan, Leucovorin, 5-FluorouracilOxaliplatin 100 mg/m² infusion in 2 hours, Cetuximab 500mg/m² infusion in 2 hours, Bevacizumab 5 mg/kg infusion in 30 minutes, Panitumumab 6 mg/kg, Irinotecan 180 mg/m² over 90 minutes to begin 30 minutes after folinic acid infusion is started, Leucovorin 400 mg/m² infusion in 2 hours, 5-Fluorouracil 2400 mg/m² infusion continuous in 46h | Drug | HAI oxaliplatin combined with I.V. FOLFIRI + target therapy, conventional systemic CT |
Primary outcome
Curative-intent (R0-R1) resection (and/or ablation) rate (CRR) of CRLM
Time frame: 6 months
Curative-intent (R0-R1) resection (and/or ablation) rate (CRR) of CRLM confirmed by a systematic review of the surgical and pathological report by an independent committee blind to the treatment received
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2024.
- Derived from this study: PubMed 41118066Boileve A, Audemar F, Dupont-Bierre E, Le Sourd S, Ulusakarya A, Chauvenet M, Benmaziame A, Wagner M, Goere D, Dromain C, Gelli M, Pezzella V, Bonnet B, Tanguy ML, Boige V. Treatment Intensification with Hepatic Arterial Infusion Chemotherapy in Patients with Liver-Only Colorectal Metastases Still Unresectable After Systemic Induction Chemotherapy: Exploratory Findings From a Prematurely Closed Multicenter Randomized Phase II Study: SULTAN UCGI 30/PRODIGE 53 (NCT03164655). Ann Surg Oncol. 2026 Feb;33(2):1460-1469. doi: 10.1245/s10434-025-18570-5. Epub 2025 Oct 21.
- Derived from this study: PubMed 32000724Boileve A, Maillard A, Wagner M, Dromain C, Laurent C, Dupont Bierre E, Le Sourd S, Audemar F, Ulusakarya A, Guerin-Meyer V, Smisth D, Pezzella V, De Baere T, Goere D, Gelli M, Taieb J, Boige V. Treatment intensification with hepatic arterial infusion chemotherapy in patients with liver-only colorectal metastases still unresectable after systemic induction chemotherapy - a randomized phase II study -- SULTAN UCGI 30/PRODIGE 53 (NCT03164655)- study protocol. BMC Cancer. 2020 Jan 30;20(1):74. doi: 10.1186/s12885-020-6571-7.
- Individual participant dataSharing planned: Yes. Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
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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.
Valérie Boige principal investigator
Gustave Roussy Villejuif
4 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 Oxaliplatin, Cetuximab, Bevacizumab, Panitumumab, Irinotecan, Leucovorin, 5-Fluorouracil in people with Colorectal Cancer Metastatic, run by UNICANCER at 4 sites 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 17 inclusion and 34 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 1 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Curative-intent (R0-R1) resection (and/or ablation) rate (CRR) of CRLM (time frame: 6 months). 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 NCT03164655, which also lists 2 linked publications.
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 1 Oct 2024.