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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Gustave Roussy, Cancer Campus, Grand Paris
Merck Serono International SA
Pfizer
CRESGE
Information provided by (Responsible Party):
Association pour la Recherche sur le Temps Biologique et la Chronothérapie
ClinicalTrials.gov Identifier:
NCT00852228
First received: February 25, 2009
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

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).


Condition Intervention Phase
Metastatic Colorectal Cancer
Liver Metastases
Hepatic Lesions
Drug: IV cetuximab
Drug: HAI chronomodulated chemotherapy
Drug: HAI conventional chemotherapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Optimal Control of Liver Metastases With Intravenous Cetuximab and Hepatic Artery Infusion of Three-drug Chemotherapy in Patients With Liver-only Metastases From Colorectal Cancer. A European Multicenter Phase II Trial

Resource links provided by NLM:


Further study details as provided by Association pour la Recherche sur le Temps Biologique et la Chronothérapie:

Primary Outcome Measures:
  • Incidence of complete macroscopic resections (R0+R1) of unresectable liver metastases following chemotherapy. [ Time Frame: evaluation every 6th week up to 18 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The rate and site(s) of relapse in the resected patients throughout the 3-year span that follows hepatectomy [ Time Frame: every 2 month up to 3 years ] [ Designated as safety issue: No ]
  • The relapse-free survival in the resected patients [ Time Frame: every 2nd month up to 3 years ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: every 2nd month up to 3 years ] [ Designated as safety issue: No ]
  • The objective response rate [ Time Frame: every 6 weeks up to 18 weeks ] [ Designated as safety issue: No ]
  • The rate of adverse events [ Time Frame: continuous up to 30 days following end of treatment ] [ Designated as safety issue: Yes ]
  • The per-operative and post-operative complications associated to liver surgery [ Time Frame: continuous up to 3 months following surgery ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: July 2008
Estimated Study Completion Date: December 2015
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: chronomodulated HAI chemotherapy Drug: IV cetuximab
Cetuximab is administered every two weeks at the dose of 500 mg/m² over 2h30 (150 minutes).
Other Name: Erbitux
Drug: HAI chronomodulated chemotherapy

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.

Other Names:
  • Campto
  • Eloxatin
Experimental: conventional HAI chemotherapy Drug: IV cetuximab
Cetuximab is administered every two weeks at the dose of 500 mg/m² over 2h30 (150 minutes).
Other Name: Erbitux
Drug: HAI conventional chemotherapy

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.

Other Names:
  • Campto
  • Eloxatin

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • Histologically or cytologically confirmed carcinoma of the colon and/or rectum with evidence of liver metastases (new confirmation of metastatic disease is required in case the time interval from last histological diagnosis to enrolment exceeds 3 years).
  • Patient with wild type (WT) KRAS tumor status
  • Patient whose liver metastases are considered to be non resectable with curative intent in medico-surgical staff meeting. In particular patients with at least one of the following criteria, which prevent complete local treatment of liver metastasis with surgery alone or surgery plus radiofrequency ablation because:

    • less than 30% estimated residual liver after resection
    • disease in contact with liver main vessels
    • documented progressive disease on imaging documents or doubling of serum levels of carcino-embryonic antigen (CEA) or CA19.9 over the past 90 days or less
  • Patient with up to three resectable extrahepatic nodules of <= 10 mm
  • One, two or three prior chemotherapy lines for colorectal cancer.
  • Written informed consent.
  • Age >=18 years.
  • Patient must be able to comply with the protocol.
  • Life expectancy of at least 3 months.
  • At least one measurable metastatic liver lesion (as per RECIST criteria).
  • World Health Organization performance status of 0 or 1.
  • Adequate hematological function: absolute neutrophil count (ANC) >=1.0 x 10^9/L; platelets >=75 x 10^9/L, hemoglobin (Hb) >=8.5 g/dL.
  • International normalized ratio (INR) <=1.5 and activated partial thromboplastin time (aPTT) <=1.5 x upper limit of normal (ULN) within 7 days prior to starting study treatment, in the absence of anticoagulant therapy.
  • Liver function: serum bilirubin <=1.5 x ULN; alkaline phosphatase and transaminases <5 x ULN (liver metastases).
  • Serum creatinine <= 1.5 x ULN.
  • Fertile women and men of childbearing potential (<2 years after last menstruation in women) must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile).

Exclusion Criteria:

  • 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.

Prior systemic administration of cetuximab or other anti-EGFR agent is not an exclusion criterion.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00852228

Locations
Belgium
Clinique Saint-Joseph
Liège, Belgium, 4000
France
CHU de Bordeaux, Hôpital Saint-André
Bordeaux, France, 33000
Hôpital Ambroise Paré
Boulogne-Billancourt, France, 92100
Centre Jean Perrin
Clermont-Ferrand, France, 63011
CHRU de Lille, Hôpital Claude Huriez
Lille, France, 59037
Hôpital Européen Georges Pompidou
Paris, France, 75015
Hôpital Cochin
Paris, France, 75014
CHU Toulouse
Toulouse, France, 31059
Chronotherapy Unit, Medical Oncology Department, Paul Brousse Hospital
Villejuif, France, 94800
Institut Gustave Roussy
Villejuif, France, 94800
Italy
Università G. d'Annunzio
Chieti, Italy, 66100
Azienda Ospedaliera S.Maria Degli Angeli
Pordenone, Italy, 33170
Istituto Regina Elena
Roma, Italy, 00144
Portugal
Hospital Fernando Fonesca
Amadora, Portugal, 27000
Sponsors and Collaborators
Association pour la Recherche sur le Temps Biologique et la Chronothérapie
Gustave Roussy, Cancer Campus, Grand Paris
Merck Serono International SA
Pfizer
CRESGE
Investigators
Principal Investigator: Francis A. Lévi, M.D., Ph.D. Paul Brousse Hospital, Villejuif, France
  More Information

No publications provided

Responsible Party: Association pour la Recherche sur le Temps Biologique et la Chronothérapie
ClinicalTrials.gov Identifier: NCT00852228     History of Changes
Other Study ID Numbers: OPTILIV07, EUDRACT number: 2007-004632-24
Study First Received: February 25, 2009
Last Updated: December 10, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: National Consultative Ethics Committee for Health and Life Sciences
Italy: The Italian Medicines Agency

Keywords provided by Association pour la Recherche sur le Temps Biologique et la Chronothérapie:
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

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Liver Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Liver Diseases
Fluorouracil
Oxaliplatin
Cetuximab
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 15, 2014