Study Comparing Pathological Responses Observed on Colorectal Cancer Metastases Resected After Preoperative Bevacizumab With FOLFOX or FOLFIRI. (BEV-ONCO2012)

October 20, 2020 updated by: Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Randomized Phase 2 Study Comparing Pathological Responses on Colorectal Cancer Metastases After Preoperative Treatment Combining Bevacizumab With FOLFOX or FOLFIRI

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Bouge, Belgium, 5004
        • Clinique Saint Luc
      • Brussels, Belgium, 1200
        • Cliniques Universitaires Saint-luc
      • Brussels, Belgium, 1180
        • CHIREC
      • Charleroi, Belgium, 6000
        • Grand Hôpital de Charleroi
      • Kortrijk, Belgium, 8500
        • Az Groeninge
      • La Louvière, Belgium, 7100
        • Centre Hospitalier Jolimont Lobbes
      • Liège, Belgium, 4000
        • CHC Liège clinique Saint Joseph
      • Liège, Belgium, 4000
        • CHU liège (Sart Timan)
      • Namur, Belgium, 5000
        • Clinique Maternité Saint Elisabeth
      • Ottignies, Belgium, 1340
        • Clinique Saint Pierre Ottignies
      • Yvoir, Belgium, 5530
        • CHU-UCL Dinant-Godinne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Folfox: oxaliplatin +leucovorin+ 5FU
FOLFOX (oxaliplatin +leucovorin+ 5FU) +bevacizumab+ metastases resection
Procedure: Metastases resection
Surgery of colorectal cancer metastases will be proceeded after 3 to 6 cycles of chemotherapy ( folfox or folfiri) + bevacizumab .
Drug: Bevacizumab
Bevacizumab 5 mg/kg in 100 ml NaCl 0.9% IV infusion 3 to 5 cycles. No bevacizumab for ultimate cycle .
Other Names:
  • Avastin
Drug: 5 FU
Leucovorin L (levoleucovorin) 200 mg/m2 (or folinic acid 400 mg/m²) in 250 ml glucose 5%, IV infusion 3 to 6 cycles 5-FU bolus 400 mg/m2, IV bolus 3 to 6 cycles 5-FU continuous infusion 2400 mg/m2, 46-hour cont. IV infusion 3 to 6 cycles
Other Names:
  • 5-Fluorouracile
Drug: Oxaliplatin
oxaliplatin 85 mg/m² in 150 ml NaCl 0.9%, IV infusion 3 to 6 cycles
Other Names:
  • Eloxatin
Active Comparator: FOLFIRI: irinotecan+leucovorin+5FU
FOLFIRI (irinotecan+leucovorin+5FU) +bevacizumab +metastases resection
Procedure: Metastases resection
Surgery of colorectal cancer metastases will be proceeded after 3 to 6 cycles of chemotherapy ( folfox or folfiri) + bevacizumab .
Drug: Bevacizumab
Bevacizumab 5 mg/kg in 100 ml NaCl 0.9% IV infusion 3 to 5 cycles. No bevacizumab for ultimate cycle .
Other Names:
  • Avastin
Drug: 5 FU
Leucovorin L (levoleucovorin) 200 mg/m2 (or folinic acid 400 mg/m²) in 250 ml glucose 5%, IV infusion 3 to 6 cycles 5-FU bolus 400 mg/m2, IV bolus 3 to 6 cycles 5-FU continuous infusion 2400 mg/m2, 46-hour cont. IV infusion 3 to 6 cycles
Other Names:
  • 5-Fluorouracile
Drug: Irinotecan
Irinotecan 180 mg/m² in 150 ml NaCl 0.9%, IV infusion 3 to 6 cycles
Other Names:
  • Campto
  • Irinosin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the major pathological response rate
Time Frame: 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
After surgery (Metastases resection-average 3 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: at 6 months and at 12 months after randomization
at 6 months and at 12 months after randomization
Overall Survival
Time Frame: 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)
At the end of the study
Clinical Response Rate
Time Frame: At time of surgery - average 3 months
At time of surgery - average 3 months
Metabolic Response Rate
Time Frame: At time of surgery - Average 3 months
At time of surgery - Average 3 months
Post operative complication
Time Frame: One month after surgery
One month after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Collaborators

Grand Hôpital de Charleroi

Investigators

  • Principal Investigator: Marc Van den Eynde, MD, Cliniques Universitaires Saint-luc
  • Principal Investigator: Javier Carrasco, MD PhD, Grand Hôpital de Charleroi - Notre-Dame

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2013

Primary Completion (Actual)

May 1, 2019

Study Completion (Actual)

May 1, 2019

Study Registration Dates

First Submitted

May 7, 2013

First Submitted That Met QC Criteria

May 20, 2013

First Posted (Estimate)

May 21, 2013

Study Record Updates

Last Update Posted (Actual)

October 22, 2020

Last Update Submitted That Met QC Criteria

October 20, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BEV-ONCO2012
  • 2012-005376-34 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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