Study Comparing Pathological Responses Observed on Colorectal Cancer Metastases Resected After Preoperative Treatment Combining Cetuximab With FOLFOX or FOLFIRI in RAS and B-RAF WT Tumors

NCT01858662 | Terminated Phase 2 DMC

• 2 other identifiers: CET-ONCO20122012-005249-19
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 7

Brief Summary

To analyze the pathological tumor response on resected colorectal cancer metastases after preoperative treatment with cetuximab combined with FOLFOX or FOLFIRI regimen in a prospective cohort (RAS and B-RAF WT tumors) and to correlate this response with patient's outcome.

Conditions

Metastatic Colorectal Cancer

Keywords

metastatic colorectal cancer; Liver; cetuximab; Pathological response

Outcome Measures

Primary Outcomes (1)

• Major Pathological Response Rate

  Major pathological response rate (MPRR) is defined as the proportion of patients presenting a major pathological response. Pathologic response will be evaluated according the Rubbia-Brandt Tumor Regression Grade classification .For patients with multiple colorectal metastases the global pathological response will be categorized based on the mean TRG of all metastases.: a major response is defined as a mean TRG \< 3, a partial response is defined for patient presenting a mean TRG ≥3 and \<4, and a no response for patient with a mean TRG ≥4.

  Average 3 months (after resection of metastases)

Secondary Outcomes (7)

• progression free survival

  at 6 months and at 12 months after randomization

• Overall survival

  At the end of the study

• Clinical response rate

  at time of surgery -

• Metabolic response rate

  At time of surgery - average 3 months

• post operative complications

  one month after surgery

Study Arms (2)

oxaliplatin +leucovorin L+5FU+ cetuximab

ACTIVE COMPARATOR

oxaliplatin +leucovorinL+5-Fluorouracile +cetuximab+'Metastases Resection ( multiple steep surgery possible)

Procedure: Metastases Resection ( multiple steep surgery possible); Drug: 5-Fluorouracile; Drug: leucovorin L; Drug: Oxaliplatin; Drug: Cetuximab

Irinotecan+ + leucovorinL +5-Fluorouracil +cetuximab

ACTIVE COMPARATOR

Irinotecan+ + leucovorinL +5-Fluorouracile + cetuximab +'Metastases Resection ( multiple steep surgery possible)

Procedure: Metastases Resection ( multiple steep surgery possible); Drug: 5-Fluorouracile; Drug: leucovorin L; Drug: Irinotecan; Drug: Cetuximab

Interventions

Metastases Resection ( multiple steep surgery possible) PROCEDURE

Metastases resection will be process by surgery, after a randomized chemotherapy (FOLFOX or FOLFIRI) + Target therapy (Cetuximab). The surgery will allow to compare the pathological response on the resected metastases by the chemotherapy + target therapy type.

Irinotecan+ + leucovorinL +5-Fluorouracil +cetuximab; oxaliplatin +leucovorin L+5FU+ cetuximab

5-Fluorouracile DRUG

5-FU bolus 400 mg/m2, IV bolus every 2 weeks 5-FU continuous infusion 2400 mg/m2, 46-hour cont. IV infusion every 2 weeks

Also known as: 5FU

Irinotecan+ + leucovorinL +5-Fluorouracil +cetuximab; oxaliplatin +leucovorin L+5FU+ cetuximab

leucovorin L DRUG

Leucovorin L (levoleucovorin) 200 mg/m2 (or folinic acid 400 mg/m²) in 250 ml glucose 5%, 2-hour IV infusion

Also known as: elvorine, isovorin

Irinotecan+ + leucovorinL +5-Fluorouracil +cetuximab; oxaliplatin +leucovorin L+5FU+ cetuximab

Oxaliplatin DRUG

Oxaliplatin 85 mg/m² in 150 ml NaCl 0.9%, 2-hour IV infusion every 2 weeks

Also known as: Eloxatin

oxaliplatin +leucovorin L+5FU+ cetuximab

Irinotecan DRUG

Irinotecan 180 mg/m² in 150 ml NaCl 0.9%, 1.30-hour IV infusion every 2 weeks

Also known as: Campto, Irinosin

Irinotecan+ + leucovorinL +5-Fluorouracil +cetuximab

Cetuximab DRUG

Cetuximab 400 mg/m² in 100 ml NaCl 0.9% 2-hour IV infusion for 1rst cycle and after the 1rst cycle 250 mg/m² in 100 ml NaCl 0.9% 1-hour IV infusion

Also known as: erbitux

Irinotecan+ + leucovorinL +5-Fluorouracil +cetuximab; oxaliplatin +leucovorin L+5FU+ cetuximab

Eligibility Criteria

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

You may qualify if:

• Female or male patients with at least 18 years at the time the informed consent is signed
• ECOG performance status 0 or 1
• Histological or cytological confirmed diagnostic of adenocarcinoma of the colon or rectum, with or without primary tumour in situ. Wild-type RAS and B-RAF tumor status.
• Patients with potentially resectable metastatic disease at diagnosis and for whom a chemotherapy first in a curative intent is recommended . Resectability could be planed in one or multiple stage if indicated. As commonly admitted, resectability means the surgical clearance (+/- radiofrequency ablation) of all detectable (liver) lesions with tumor-free margins and compatible with an adequate hepatic reserve. Practically, bilateral tumor location, number and location of lesions, and inadequate hepatic reserve remain the main decisional factors.
• Extra hepatic metastatic location is limited to 1 site.
• Adequate haematological, renal and hepatic function as follows:
• Haematological:
• haemoglobin \>9g/dl Neutrophils \> 1.5 x 109/L Platelets \> 100 x 109/L
• Renal:
• Creatinine\< 1.5 x ULN (Upper Limit of Normal)
• Hepatic:
• Bilirubin \< or equal 1.5 X ULN AST (Aspartate Aminotransferase),and ALT (Alanine Aminotransferase)\< or equal 5 x ULN, Phos Alc\< or equal 5 x ULN
• Female patients must either be postmenopausal, sterile (surgically or radiation- or chemically-induced), or if sexually active using an acceptable method of contraception.
• Male patients must be surgically sterile or if sexually active and having a pre-menopausal partner must be using an acceptable method of contraception.
• Life expectancy of at least 3 months without any active treatment.

You may not qualify if:

• Definitively non resectable mCRC at diagnosis
• Prior utilization of cetuximab, panitumumab (or other anti-EGFR (epidermal growth factor receptor)therapy).
• Previous radiotherapy delivered to the upper abdomen.
• Non mesurable disease( RECIST 1.1 criteria)
• Evidence of ascites, cirrhosis, portal hypertension, main portal venous tumour involvement or thrombosis as determined by clinical or radiologic assessment.
• Prior major liver resection: remnant liver \< 50% of the initial liver volume.
• Non-malignant disease that would render the patient unsuitable for treatment according to this protocol.
• Concurrent central nervous systems metastases
• Peripheric neuropathy ≥ grade 2.
• Interstitial lung disease
• Pregnant or breast feeding.
• The patient has previous or concomitant malignancies, except: Invasive malignancies in remission for more than 5 years and non melanoma skin cancer or carcinoma in situ of the cervix.

Sponsors & Collaborators

• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: lead
• Grand Hôpital de Charleroi: collaborator

Study Sites (7)

Cliniques universitaires Saint-Luc - UCL

Brussels, Brussels Capital, 1200, Belgium

Location

Grand Hôpital de Charleroi

Charleroi, Hainaut, 6000, Belgium

Location

clinique Saint Luc

Bouge, 5004, Belgium

Location

Centre Hospitalier Jolimont Lobbes

La Louvière, 7100, Belgium

Location

CHU liège (Sart Timan)

Liège, 4000, Belgium

Location

Clinique Saint Pierre Ottignies

Ottignies, 1340, Belgium

Location

CHU-UCL Dinant-Godinne

Yvoir, 5530, Belgium

Location

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MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil; Leucovorin; Oxaliplatin; Irinotecan; Cetuximab

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)

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

Study Officials

• Marc Van den Eynde, MD

  Cliniques universitaires Saint-Luc - UCL

  PRINCIPAL INVESTIGATOR

• Javier Carrasco, MD PhD

  Grand Hôpital de Charleroi

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 7, 2013
• First Posted: May 21, 2013
• Study Start: January 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: April 15, 2016

Record last verified: 2016-04

Locations

BE (7)