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Recruiting Phase 3

Systemic Oxaliplatin or Intra-arterial Chemotherapy Combined With LV5FU2 +/- Irinotecan and an Target Therapy in First Line Treatment of Metastatic Colorectal Cancer Restricted to the Liver

NCT02885753 · tracked via the Priya Life Science France tracker
Phase
Phase 3
Started
2016-12
Last updated
2025-07-09

Condition(s) studied

Colorectal Neoplasms

Investigational drug(s) / intervention(s)

Oxaliplatin intravenous →5 FU bolus →Folinic acid →Oxaliplatin intra-arterielPanitumumab →Bevacizumab →5 FU continuous →Irinotecan →

Oxaliplatin intravenous: 85 mg/m² in intravenous. 1 cycle each 15 days

5 FU bolus: 5 fluorouracil : 400 mg/m² in bolus of 10 minutes (intravenous) following by 2400 mg/m² during 46 hours in intravenous

Folinic acid: 400 mg/m² in intravenous

Oxaliplatin intra-arteriel: 85 mg/m² in intra-arterial. 1 cycle each 15 days

Panitumumab: Only for patient RAS wild: 6 mg/Kg at each cycle in intravenous

Bevacizumab: 5 mg/kg at each cycle in intravenous

5 FU continuous: 2400 mg/m² intravenously over 46 hours

Irinotecan: 150 mg/m² intravenous

Study summary

Colorectal cancer is the 3rd most common cancer in France and the 2nd cause of death from cancer. Between 30 to 60% of patients develop limited or predominant liver metastases. Surgical resection of these metastases, only curative treatment is not immediately possible in 10-15% of cases. In unresectable patients, current palliative treatments are based on systemic chemotherapy associated or not with the targeted therapies (anti-EGFR (panitumumab), anti-VEGF (bevacizumab)). In this patient population, special attention was paid to intensified treatment regimens in order to improve their efficiency and improving the tumoral response rate, the intensity of the response and its earliness correlate with improved overall and progression-free survival.

The intra-arterial use of oxaliplatin coupled with IV chemotherapy has yielded OR levels of 64% in patients having survived one or more lines of chemotherapy IV and 62% in patients who have progressed on oxaliplatin IV. In addition, the HIA administration of oxaliplatin limits systemic and especially neurological toxicities, thanks to a greater hepatic clearance.

In conclusion, the combination of systemic chemotherapy, targeted therapy and HIAC with oxaliplatin has showed promising efficacy results associated with good tolerance from the first line onwards. Indeed, we can expect from the Phase II recent data, a control rate close to 100%, with high response rates associated with early maturity and depth responses as well as prolonged survival. However, to date, in the absence of randomized trial testing this combination, this strategy does not have sufficient evidence to be integrated in our routine practices, and HIAC remains limited to a few expert centers in treatment catch-up.

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria: * Histologically proven colorectal adenocarcinoma with hepatic metastasis(es) * At least one measurable hepatic metastasis according to the criteria RECIST v1.1 * No other metastatic sites except lung nodules if number ≤ 3 and \< 10 mm * RAS mutation status known (determination of KRAS mutation (exons 2,3 and 4) and determination of the NRAS mutation (exons 2,3 and 4)) * Age ≥ 18 * WHO ≤ 2 (Appendix 4) * No prior treatment by chemotherapy except perioperative or adjuvant chemotherapy discontinued for more than 12 months * Life expectancy \> 3 months * PNN \> 1500/mm3, platelets \> 100 000/mm3, Hb \> 9 g/dLq * Bilirubin \< 25 mmol/L, AST \< 5x ULN, ALT \< 5 x ULN, ALP \< 5 x ULN, TP \> 60%, proteinuria from 24H \< 1 g * Creatinine clearance \> 50 mL/min according to MDRD formula (Appendix 4) * Patient affiliated to a social security scheme * Patient information and signature of the informed consent Exclusion Criteria: * Contraindications specific to the installation of a KTHIA: thrombosis of the hepatic artery, arterial vascular anatomy may compromise a secondary hepatic resection. * Patient immediately eligible for a curative therapy (surgical and/or percutaneous) after discussion in CPR * Following alterations in the 6 months prior to inclusion: myocardial infarction, angina, severe/unstable angina, coronary artery bypass surgery, congestive heart failure NYHA class II, III or IV, stroke or transient ischemic attack * Hypertension not controlled by medical treatment (SBP \> 140 mmHg and/or DBP\> 90 mmHg with blood pressure taken according to the diagram of the HAS) * A history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or active gastrointestinal bleeding in the 6 months preceding the start of treatment * Progressive gastroduodenal ulcer, wound or fractured bone * Abdominal or major extra-abdominal surgery (except diagnostic biopsy) or irradiation in the 4 weeks before starting the treatment * Transplant patients, HIV positive or other immune deficiency syndromes * Any progressive pathology not balanced over the past 6 months: hepatic failure, renal failure, respiratory failure * Peripheral neuropathy \> 1 * Patient with interstitial pneumonitis or pulmonary fibrosis * History of chronic diarrhea or inflammatory disease of the colon or rectum, or unresolved occlusion or sub-occlusion in symptomatic treatment * History of malignant pathologies during the past 5 years except basocellular skin carcinoma considered in complete remission or in situ cervical carcinoma, properly treated * Patient already included in another clinical trial with an experimental molecule * Any known specific contraindication or allergy or hypersensitivity to the drugs used in the study (cf RCP Appendix 7) * Known deficit in DPD * QT/QTc range \> 450 msec for men and \> 470 msec for women * K+ \< LNL, Mg2+ \< LNL, Ca2+ \< LNL * Lack of effective contraception in patients (men and/or women) of childbearing age, pregnant or breastfeeding women, women of childbearing age not having had a pregnancy test * Persons deprived of liberty or under supervision * Impossibility of undergoing medical monitoring during the trial for geographic, social or psychological reasons

Primary outcome measure(s)

  • progression-free survival — 24 months after randomization
    comparison of radiological/clinical progression free survival

Trial sites (49)

FacilityCityRegionStatus
Hôpital Erasme Brussels Belgium Recruiting
Chu Hotel Dieu Angers France Recruiting
Institut de Cancérologie de l'Ouest Angers France Recruiting
Hôpital Privé d'Antony Antony France Recruiting
CH Henri Duffaut Avignon France Not Yet Recruiting
Institut du cancer Avignon Provence Avignon France Recruiting
Ch Cote Basque Bayonne France Recruiting
Clinique Belharra Bayonne France Recruiting
Centre Hospitalier Beauvais France Not Yet Recruiting
Institut Bergonié Bordeaux France Recruiting
Polyclinique Bordeaux Nord Bordeaux France Recruiting
Infirmerie Protestante de Lyon Caluire-et-Cuire France Recruiting
CH Loire Vendée Océan Challans France Not Yet Recruiting
Centre Hospitalier Sud Francilien Corbeil-Essonnes France Recruiting
Chu Le Bocage Dijon France Not Yet Recruiting
Chd Vendee La Roche-sur-Yon France Recruiting
Groupe Hospitalier de la Rochelle Re-Aunis La Rochelle France Recruiting
Ch de Bicetre Le Kremlin-Bicêtre France Not Yet Recruiting
GH Nord Essone Longjumeau France Not Yet Recruiting
Hôpital du Scorff Lorient France Recruiting
Centre Léon Bérard Lyon France Recruiting
Hôpital de la Croix Rousse Lyon France Recruiting
Hôpital Européen Marseille France Recruiting
Hôpital Saint-Joseph Marseille France Recruiting
Institut Paoli Calmettes Marseille France Not Yet Recruiting
Chu Hotel Dieu Nantes France Recruiting
CHR La Source Orléans France Not Yet Recruiting
Hôpital Cochin Paris France Not Yet Recruiting
Hôpital Saint Joseph Paris France Recruiting
Hôpital Saint Louis Paris France Recruiting
Paris Hôpital Européen Georges Pompidou Paris France Recruiting
Centre Hospitalier Pau France Recruiting
Centre Hospitalier Saint Jean Perpignan France Recruiting
CHU Haut Lévêque Pessac France Recruiting
CHU La Milétrie Poitiers France Recruiting
Centre Eugène Marquis Rennes France Recruiting
Clinique Pasteur Ris-Orangis France Not Yet Recruiting
CROME Ris-Orangis France Not Yet Recruiting
CHU Charles Nicolle Rouen France Recruiting
CHP Saint-Grégoire France Recruiting

+ 9 more sites — see the full list on the official registry below.

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT02885753 on ClinicalTrials.gov ↗ ← All trials in France