Study Comparing Pathological Responses Observed on Colorectal Cancer Metastases Resected After Preoperative Bevacizumab With FOLFOX or FOLFIRI.

Phase 2

Completed

• Conditions: Metastatic Colorectal Cancer
• Interventions: Procedure: Metastases resection; Drug: Bevacizumab; Drug: 5 FU; Drug: Oxaliplatin; Drug: Irinotecan

• Registration Number: NCT01858649
• Lead Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Brief Summary

The study is designed to analyze the pathological tumor response on resected colorectal cancer metastases after preoperative treatment with bevacizumab combined with FOLFOX or FOLFIRI regimen in a prospective cohort and to correlate this response with patient's outcome.

Detailed Description

This is a phase II , openlabel, randomized study in patients with confirmed diagnosis of resectable metastatic colorectal adenocarcinoma , who have not received prior chemotherapy for their metastatic disease. The study is designed to compare pathological responses observed after pre-operative chemotherapy bevacizumab with FOLFOX or FOLFIRI.

Study Timeline

• Study Start: 2013-05
• Study First Submitted: 2013-05-07
• Study First Submitted QC: 2013-05-20
• Study First Posted: 2013-05-21
• Primary Completion: 2019-05
• Study Completion: 2019-05
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-20
• Last Update Posted: 2020-10-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• 1. Female or male patients with at least 18 years at the time the informed consent is signed
• 2.ECOG (Eastern Cooperative Oncology Group)performance status 0 or 1
• 3.Histological or cytological confirmed diagnostic of adenocarcinoma of the colon or rectum, with or without primary tumour in situ. Wild-type or mutated KRAS tumor status.
• 4.Patients must present a resectable metastatic disease for which the decision of preoperative chemotherapy is considered. Resectability could be planned 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.
• 5.Partial and minor resection of metastatic disease is allowed within 3 months before inclusion if patient has never received chemotherapy for mCRC.
• 6.Extra hepatic metastatic location is limited to 1 site. Extra-hepatic location must be easily resectable in one stage surgery.
• 7.Patients may have received adjuvant chemotherapy or (neo-) adjuvant chemo-radiotherapy to the pelvis, provided the last dose of chemotherapy was administered at least 6 months prior to inclusion (12 months for oxaliplatin). Previous radiotherapy to the pelvis is not an exclusion criterion.
• 8.Adequate haematological, renal and hepatic function as follows: Haematological Neutrophils > 1.5 x 109/L Platelets > 100 x 109/L Renal Creatinine < 1.5 x ULN (Upper Limit of Normal) Hepatic Bilirubin < 1.5 X ULN AST(Aspartate aminotransferase), ALT (Alanine Aminotransferase) < 5 x ULN Phos Alc. < 5 x ULN
• 9.Proteinuria <2+ (dipstick urinalysis) or =1g/24hour.
• 10.No history of myocardial infarction and/or stroke within 6 months prior to randomization. No uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure > 100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy.
• 11.Female patients must either be postmenopausal, sterile (surgically or radiation- or chemically-induced), or if sexually active using an acceptable method of contraception.
• 12.Male patients must be surgically sterile or if sexually active and having a pre-menopausal partner must be using an acceptable method of contraception.
• 13.Life expectancy of at least 3 months without any active treatment.

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Exclusion Criteria

• 1.Non resectable mCRC (metastatic ColoRectal Cancer) (if resectability remains uncertain or unprobable after 3 months chemotherapy, patient is excluded from the trial).
• 2.Prior chemotherapy or systemic therapy for mCRC. Adjuvant chemotherapy for colorectal cancer is not an exclusion criterion provided that it was completed more than 6 months prior to inclusion. Oxaliplatin-based chemotherapy must be completed more than 1 year prior to inclusion.
• 3.Prior utilization of bevacizumab, aflibercept (or other anti-VEGF(vascular endothelial growth factor) therapy).
• 4.Previous radiotherapy delivered to the upper abdomen.
• 5.Evidence of ascites, cirrhosis, portal hypertension, main portal venous tumour involvement or thrombosis as determined by clinical or radiologic assessment.
• 6.Prior major liver resection: remnant liver < 50% of the initial liver volume.
• 7.Non-malignant disease that would render the patient unsuitable for treatment according to this protocol.
• 8.Concurrent central nervous systems metastases
• 9.Peripheric neuropathy ≥ grade 2.
• 10.Interstitial lung disease
• 11.Pregnant or breast feeding.
• 12.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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FOLFIRI: irinotecan+leucovorin+5FU	5 FU	FOLFIRI (irinotecan+leucovorin+5FU) +bevacizumab +metastases resection
Folfox: oxaliplatin +leucovorin+ 5FU	Metastases resection	FOLFOX (oxaliplatin +leucovorin+ 5FU) +bevacizumab+ metastases resection
Folfox: oxaliplatin +leucovorin+ 5FU	5 FU	FOLFOX (oxaliplatin +leucovorin+ 5FU) +bevacizumab+ metastases resection
FOLFIRI: irinotecan+leucovorin+5FU	Metastases resection	FOLFIRI (irinotecan+leucovorin+5FU) +bevacizumab +metastases resection
Folfox: oxaliplatin +leucovorin+ 5FU	Oxaliplatin	FOLFOX (oxaliplatin +leucovorin+ 5FU) +bevacizumab+ metastases resection
Folfox: oxaliplatin +leucovorin+ 5FU	Bevacizumab	FOLFOX (oxaliplatin +leucovorin+ 5FU) +bevacizumab+ metastases resection
FOLFIRI: irinotecan+leucovorin+5FU	Bevacizumab	FOLFIRI (irinotecan+leucovorin+5FU) +bevacizumab +metastases resection
FOLFIRI: irinotecan+leucovorin+5FU	Irinotecan	FOLFIRI (irinotecan+leucovorin+5FU) +bevacizumab +metastases resection

Primary Outcome Measures

Name	Time	Method
the major pathological response rate	After surgery (Metastases resection-average 3 months)	This is at the surgery time. The metastases resection must be process after 6 cycles of randomized chemotherapy + target therapy. It depend but it will be normally 3 months after patient inclusion in the study

Secondary Outcome Measures

Name	Time	Method
Clinical Response Rate	At time of surgery - average 3 months
Metabolic Response Rate	At time of surgery - Average 3 months
Progression free survival	at 6 months and at 12 months after randomization
Post operative complication	One month after surgery
Overall Survival	At the end of the study	The overall survival will be analyzed at the end of the study (3 years of recruitment and one years of follow-up)

Trial Locations

Locations (11)

Clinique Saint Luc; 🇧🇪 Bouge, Belgium

AZ Groeninge; 🇧🇪 Kortrijk, Belgium

CHU-UCL Dinant-Godinne; 🇧🇪 Yvoir, Belgium

Centre Hospitalier Jolimont Lobbes; 🇧🇪 La Louvière, Belgium

Cliniques universitaires Saint-Luc; 🇧🇪 Brussels, Belgium

Grand Hopital de Charleroi; 🇧🇪 Charleroi, Belgium

CHU liège (Sart Timan); 🇧🇪 Liège, Belgium

CHIREC; 🇧🇪 Brussels, Belgium

CHC Liège clinique Saint Joseph; 🇧🇪 Liège, Belgium

Clinique Maternité Saint Elisabeth; 🇧🇪 Namur, Belgium

Clinique Saint Pierre Ottignies; 🇧🇪 Ottignies, Belgium