Improving SUrgery of Liver Metastases: a Trial of the Arterial Chemotherapy Network

NCT03164655 | Completed Phase 2 DMC

• 2 other identifiers: UCGI 30 - PRODIGE 53 SULTAN2016-001493-15
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

Brief 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 induction chemotherapy.

Conditions

Colorectal Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• 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

  6 months

Study Arms (2)

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

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

Drug: Oxaliplatin, Cetuximab, Bevacizumab, Panitumumab, Irinotecan, Leucovorin, 5-Fluorouracil

Interventions

Oxaliplatin, Cetuximab, Bevacizumab, Panitumumab, Irinotecan, Leucovorin, 5-Fluorouracil DRUG

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

HAI oxaliplatin combined with I.V. FOLFIRI + target therapy; conventional systemic CT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)
• Disease progression after FOLFOXIRI/FOLFIRINOX
• Sensory neuropathy ≥ grade 2 (National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.4.0)
• 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.
• Interstitial lung disease,
• Pulmonary fibrosis.
• Significant chronic liver disease (resulting in portal hypertension and/or liver insufficiency)

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (4)

Ico Paul Papin

Angers, France

Location

Centre Eugene Marquis

Rennes, France

Location

Chp Saint Gregoire

Saint-Grégoire, France

Location

Gustave Roussy

Villejuif, 94, France

Location

Related Publications (2)

• 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.

  PMID: 41118066 DERIVED

• Boileve 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.

  PMID: 32000724 DERIVED

MeSH Terms

Interventions

Oxaliplatin; Cetuximab; Bevacizumab; Panitumumab; Irinotecan; Leucovorin; Fluorouracil

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Valérie Boige

  Gustave Roussy Villejuif

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2017
• First Posted: May 23, 2017
• Study Start: July 25, 2018
• Primary Completion: July 15, 2021
• Study Completion: November 15, 2021
• Last Updated: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.
• Access Criteria: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.

Locations

FR (4)