Optimal Control of Liver Metastases From Colorectal Cancer With Cetuximab and Hepatic Artery Infusion of Chemotherapy

NCT00852228 | Unknown Phase 2 DMC

• 2 other identifiers: OPTILIV07EUDRACT number: 2007-004632-24
• Study Type: interventional
• Target: 60
• Locations: 4 countries
• Sites: 14

Brief Summary

The primary objective of the study is to increase by 15% the complete macroscopic resection rate of predominantly liver metastases from metastatic colorectal cancer through combining systemic cetuximab and hepatic artery infusion of three-drug chemotherapy (irinotecan, oxaliplatin and 5-fluorouracil).

Conditions

Metastatic Colorectal Cancer; Liver Metastases; Hepatic Lesions

Keywords

colorectal cancer; unresectable metastases; neo-adjuvant chemotherapy; liver metastases; chronotherapy; cetuximab; irinotecan; oxaliplatin; 5-fluorouracil; hepatic artery infusion; Unresectable hepatic lesions; 1 to 3 prior chemotherapy regimens

Outcome Measures

Primary Outcomes (1)

• Incidence of complete macroscopic resections (R0+R1) of unresectable liver metastases following chemotherapy.

  evaluation every 6th week up to 18 weeks

Secondary Outcomes (6)

• The rate and site(s) of relapse in the resected patients throughout the 3-year span that follows hepatectomy

  every 2 month up to 3 years

• The relapse-free survival in the resected patients

  every 2nd month up to 3 years

• The progression-free and the overall survival in the patients receiving at least 4 full courses of HAI therapy and in all the patients (intent to treat)

  every 2nd month up to 3 years

• The objective response rate

  every 6 weeks up to 18 weeks

• The rate of adverse events

  continuous up to 30 days following end of treatment

Study Arms (2)

chronomodulated HAI chemotherapy

EXPERIMENTAL

Drug: IV cetuximab; Drug: HAI chronomodulated chemotherapy

conventional HAI chemotherapy

EXPERIMENTAL

Drug: IV cetuximab; Drug: HAI conventional chemotherapy

Interventions

IV cetuximab DRUG

Cetuximab is administered every two weeks at the dose of 500 mg/m² over 2h30 (150 minutes).

Also known as: Erbitux

chronomodulated HAI chemotherapy; conventional HAI chemotherapy

HAI chronomodulated chemotherapy DRUG

Irinotecan (180 mg/m²) on day 2 as a 6 hour infusion, starting at 2:00, with a peak at 5:00 Oxaliplatin (85 mg/m²) in split daily doses for 3 days, starting on day 2. Daily sinusoidal infusion duration will last from 10:15 to 21:45, with peak delivery rate at 16:00. 5-Fluorouracil (2800 mg/m²) in split daily doses for 3 days, alternating with oxaliplatin infusions, starting on day 2. Daily sinusoidal infusions will last from 22:15 to 9:45 , with peak delivery at 4:00. Treatments will be repeated every 2 weeks.

Also known as: Campto, Eloxatin

chronomodulated HAI chemotherapy

HAI conventional chemotherapy DRUG

Irinotecan (180 mg/m²) on day 1 as a one hour infusion, then Oxaliplatin (85 mg/m²) on day 1 as a two hour infusion, then 5-Fluorouracil (2800 mg/m²) as a 48 h infusion starting on day 2, after completion of oxaliplatin delivery. Treatments will be repeated every 2 weeks.

Also known as: Campto, Eloxatin

conventional HAI chemotherapy

Eligibility Criteria

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

You may not qualify if:

• Patient whose primary tumor or metastasis displays mutation of K-Ras (codon 12 and/or 13).
• Unresectable extrahepatic diseases.
• More than three resectable extrahepatic nodules.
• Size of extra hepatic nodules \> 1 cm
• Prior HAI of the 3 drugs.
• More than 2 prior surgical attempts for metastatic disease
• Prior radiotherapy for metastatic disease
• Known documented intolerance or hypersensitivity to any of the drugs used.
• Sensory neuropathy grade 3 (National Cancer Institute-Common Terminology Criteria for Adverse Events -NCI-CTCAE, Version 3.0).
• Past or current history (within the last 2 years prior to treatment start) of malignancy other than colorectal cancer (patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible).
• Serious, non healing wound, ulcer, or bone fracture.
• Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that puts the patient at high risk for treatment-related complications.
• Pregnancy or lactation
• Fertile women (\< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.

Sponsors & Collaborators

• Association pour la Recherche sur le Temps Biologique et la Chronothérapie: lead
• Gustave Roussy, Cancer Campus, Grand Paris: collaborator
• Merck Serono International SA: collaborator
• Pfizer: collaborator
• CRESGE: collaborator

Study Sites (14)

Clinique Saint-Joseph

Liège, 4000, Belgium

Location

CHU de Bordeaux, Hôpital Saint-André

Bordeaux, 33000, France

Location

Hôpital Ambroise Paré

Boulogne-Billancourt, 92100, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

CHRU de Lille, Hôpital Claude Huriez

Lille, 59037, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Hôpital Européen Georges Pompidou

Paris, 75015, France

Location

CHU Toulouse

Toulouse, 31059, France

Location

Chronotherapy Unit, Medical Oncology Department, Paul Brousse Hospital

Villejuif, 94800, France

Location

Institut Gustave Roussy

Villejuif, 94800, France

Location

Università G. d'Annunzio

Chieti, 66100, Italy

Location

Azienda Ospedaliera S.Maria Degli Angeli

Pordenone, 33170, Italy

Location

Istituto Regina Elena

Roma, 00144, Italy

Location

Hospital Fernando Fonesca

Amadora, 27000, Portugal

Location

Related Publications (2)

• Bouchahda M, Boige V, Smith D, Karaboue A, Ducreux M, Hebbar M, Lepere C, Focan C, Guimbaud R, Innominato P, Awad S, Carvalho C, Tumolo S, Truant S, De Baere T, Castaing D, Rougier P, Morere JF, Taieb J, Adam R, Levi F; ARTBC International. Early tumour response as a survival predictor in previously- treated patients receiving triplet hepatic artery infusion and intravenous cetuximab for unresectable liver metastases from wild-type KRAS colorectal cancer. Eur J Cancer. 2016 Nov;68:163-172. doi: 10.1016/j.ejca.2016.09.011. Epub 2016 Oct 18.

  PMID: 27768923 DERIVED

• Levi FA, Boige V, Hebbar M, Smith D, Lepere C, Focan C, Karaboue A, Guimbaud R, Carvalho C, Tumolo S, Innominato P, Ajavon Y, Truant S, Castaing D, De Baere T, Kunstlinger F, Bouchahda M, Afshar M, Rougier P, Adam R, Ducreux M; Association Internationale pour Recherche sur Temps Biologique et Chronotherapie (ARTBC International). Conversion to resection of liver metastases from colorectal cancer with hepatic artery infusion of combined chemotherapy and systemic cetuximab in multicenter trial OPTILIV. Ann Oncol. 2016 Feb;27(2):267-74. doi: 10.1093/annonc/mdv548. Epub 2015 Nov 16.

  PMID: 26578731 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Irinotecan; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Francis A. Lévi, M.D., Ph.D.

  Paul Brousse Hospital, Villejuif, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2009
• First Posted: February 26, 2009
• Study Start: July 1, 2008
• Primary Completion: March 1, 2012
• Study Completion: December 1, 2015
• Last Updated: December 12, 2013

Record last verified: 2013-12

Locations

BE (1); FR (9); IT (3); PT (1)