Efficacy of FOLFOX Alone, FOLFOX Plus Bevacizumab and FOLFOX Plus Panitumumab in Patients With Resectable Liver Metastases
Conditions
Colorectal Cancer Metastatic - Liver Metastases - KRAS Wild Type Colorectal Cancer
Conditions: official terms
Colorectal Neoplasms - Liver Neoplasms - Neoplasm Metastasis
Conditions: Keywords
Liver metastases, Colorectal Cancer, KRAS wild type, FOLFOX, Bevacizumab, Panitumumab, Randomized, Phase II, Perioperative treatment, Adjuvant, Neo-adjuvant, Surgery, Progression Free Survival
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: FOLFOX6 Type: Drug
Name: Bevacizumab Type: Biological
Name: Panitumumab Type: Biological
Name: Surgery Type: Procedure
Overall Status
Recruiting
Summary
Patients presenting with multiple innumerable liver metastases will probably never come to resection, however, for all others, including patients with numerous multiple metastases or large metastases,resection should be considered after limited chemotherapy.

There is consensus for a backbone chemotherapy consisting of fluoropyrimidine + oxaliplatin. FOLFOX was used in the previous EORTC study and is again recommended.

The addition of targeted agents to standard chemotherapy in the perioperative strategy for mCRC might increase the ORR and R0 resectability, without significant increase in toxicity, therefore translating to a better outcome.

It was therefore decided to design an open label, randomized, multi-center, 3-arm late phase II study.

Arm A: (standard) mFOLFOX6 + Surgery Arm B: (experimental) mFOLFOX6 + Bevacizumab + Surgery Arm C: (experimental) mFOLFOX6 + Panitumumab + Surgery
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 75 Years
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Histologically proven CRC with 1 to 8 metachronous or synchronous liver metastases considered to be completely resectable.

- Primary tumor (or liver metastasis) of CRC must be KRAS and NRAS status "wild type".

- Patients must have undergone complete resection (R0) of the primary tumor at least 4 weeks before randomization. Or for patients with synchronous metastases the primary tumor can be resected (R0) at the same time as the liver metastases if: the patient has a non-obstructive primary tumor and is able to receive preoperative chemotherapy (3-4 months) before surgery.

- Measurable hepatic disease by RECIST version 1.1.

- Patients must be 18 years old or older.

- A WHO performance status of 0 or 1. Radiotherapy alone is allowed if given pre or post protocol treatment.

- Previous adjuvant chemotherapy for primary CRC is allowed if completed at least 12 months before inclusion in this study.

- All the following tests should be done within 4 weeks prior to randomization:

- Absolute neutrophil count ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 9 g/dL and white blood cell count (WBC) ≥ 3 x 109/L.

- Serum creatinine ≤ 1.5 times the upper limit of normal (ULN) (to exclude severe renal impairment); no significant proteinuria (urine protein < 1g/24 hours urine collection) OR urine protein/creatinine ratio < 1.0 OR 1+ proteinuria on urine dipstick.

- Absence of major hepatic insufficiency (bilirubin ≤ 1.5 x ULN and aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤ 5 x ULN).

- Magnesium ≥ lower limit of normal (LLN)

- Patients with a buffer range from the normal values of +/- 5% for hematology and +/- 10% for biochemistry are acceptable. This will not apply for Renal Function, including Creatinine.

- Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 14 days prior to the first dose of study treatment.

- Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.

- Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment.

- Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion Criteria:

- Evidence of extra-hepatic metastasis (of CRC).

- Previous chemotherapy for metastatic disease or surgical treatment (e.g. surgical resection or radiofrequency ablation) for liver metastasis.

- Previous exposure to EGFR or VEGF/VEGFR targeting therapy within the last 12 months.

- Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks prior to randomization.

- Regular use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs).

- Bleeding diathesis (e.g. hemoptysis of ≥ 1/2 teaspoon or 2.5mL), coagulopathy, or need for administration of full-dose anti-coagulant(s).

- Clinically significant cardiovascular disease, including: uncontrolled hypertension, New York Heart Association (NYHA) class II-IV heart failure, myocardial infarction or unstable angina pectoris, cerebrovascular accident or transient ischemic attack within the past 12 months, peripheral vascular disease ≥ grade 2, serious cardiac arrhythmia requiring medication and other clinically significant cardiovascular disease.

- Peripheral neuropathy > grade 1 (Common Terminology Criteria for Adverse Events, v4.0) serious wound complications, ulcers, or bone fractures.

- Symptomatic diverticulitis or active or uncontrolled gastroduodenal ulceration.

- History or evidence of interstitial lung disease (e.g. pneumonitis, pulmonary fibrosis)

- Significant disease that, in the investigator's opinion, would exclude the patient from the study. Including known allergy or any other adverse reaction to any of the study drugs (including any of the excipients) or to any related compound, including hypersensitivity to Chinese hamster ovary (CHO) cell products or other recombinant human or humanized antibodies.

- Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

- Participation in another clinical study (except sub studies of this protocol) within the 30 days before randomization and during this study.
Locations
Allgemeines Krankenhaus der Stadt Wien
Vienna, Austria
Status: Recruiting
Contact: Contact Person - 43-1-4040-2726
Hopital Universitaire Brugmann
Brussels, Belgium
Status: Recruiting
Universitair Ziekenhuis Gent
Gent, Belgium
Status: Recruiting
AZ Groeninge Kortrijk - Campus Kennedylaan
Kortrijk, Belgium
Status: Recruiting
AZ Turnhout - Campus Sint Elisabeth
Turnhout, Belgium
Status: Recruiting
Centre Hospitalier Peltzer-La Tourelle
Verviers, Belgium
Status: Recruiting
Institut Sainte Catherine
Avignon, France
Status: Recruiting
Institut Bergonie
Bordeaux, France
Status: Recruiting
CHU Ambroise Pare
Boulogne Billancourt, France
Status: Recruiting
Contact: Contact Person - 33-149-095-000
Assistance Publique - Hôpitaux de Paris - Hopital De Bicetre AP-HP
Le Kremlin Bicetre, France
Status: Recruiting
Centre Hospitalier Saint Joseph Saint Luc
Lyon, France
Status: Recruiting
Centre Leon Berard
Lyon, France
Status: Recruiting
Hopital Prive Jean Mermoz
Lyon, France
Status: Recruiting
Centre Antoine Lacassagne
Nice, France
Status: Recruiting
Groupe Hospitalier Diaconesses Croix Saint-Simon - Site Reuilly
Paris, France
Status: Recruiting
Hopital Europeen Georges Pompidou
Paris, France
Status: Recruiting
Contact: Contact Person - 33-56-092-000
CHU de Lyon - Centre Hospitalier Lyon Sud
Pierre-Benite (lyon), France
Status: Recruiting
CHU de Reims - Hôpital Robert Debré
Reims, France
Status: Recruiting
Hopital Charles Nicolle
Rouen, France
Status: Recruiting
CHU Saint-Etienne - CHU de Saint-Etienne - Hopital Nord
Saint Priest en Jarez, France
Status: Recruiting
Centre Hospitalier Privé Saint-Grégoire
Saint-Gregoire, France
Status: Recruiting
CHU d'Amiens - CHU Amiens - Hopital Sud
Salouel, France
Status: Recruiting
The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
Amsterdam, Netherlands
Status: Recruiting
Hospital General Vall D'Hebron
Barcelona, Spain
Status: Recruiting
Hôpitaux universitaires de Genève - HUG - site de Cluse-Roseraie
Geneve, Switzerland
Status: Recruiting
Start Date
June 2013
Completion Date
October 2017
Sponsors
European Organisation for Research and Treatment of Cancer - EORTC
Source
European Organisation for Research and Treatment of Cancer - EORTC
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page