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

Metastatic Colorectal Cancer Clinical Trial

— BEV-ONCO2012  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01858649
• Other study ID #: BEV-ONCO2012
• Secondary ID: 2012-005376-34
• Status: Completed
• Phase: Phase 2
• Start date: May 2013
• Est. completion date: May 2019

Study information

• Verified date: October 2020
• Source: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: May 2019
• Est. primary completion date: May 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

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 .
• 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
• Oxaliplatin
oxaliplatin 85 mg/m² in 150 ml NaCl 0.9%, IV infusion 3 to 6 cycles
• Irinotecan
Irinotecan 180 mg/m² in 150 ml NaCl 0.9%, IV infusion 3 to 6 cycles

Locations

Country	Name	City	State
Belgium	Clinique Saint Luc	Bouge
Belgium	CHIREC	Brussels
Belgium	Cliniques universitaires Saint-Luc	Brussels
Belgium	Grand Hopital de Charleroi	Charleroi
Belgium	AZ Groeninge	Kortrijk
Belgium	Centre Hospitalier Jolimont Lobbes	La Louvière
Belgium	CHC Liège clinique Saint Joseph	Liège
Belgium	CHU liège (Sart Timan)	Liège
Belgium	Clinique Maternité Saint Elisabeth	Namur
Belgium	Clinique Saint Pierre Ottignies	Ottignies
Belgium	CHU-UCL Dinant-Godinne	Yvoir

Sponsors (2)

Lead Sponsor	Collaborator
Cliniques universitaires Saint-Luc- Université Catholique de Louvain	Grand Hôpital de Charleroi

Country where clinical trial is conducted

Belgium, 

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* Note: There are 56 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the major pathological response rate	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	Progression free survival		at 6 months and at 12 months after randomization
Secondary	Overall Survival	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
Secondary	Clinical Response Rate		At time of surgery - average 3 months
Secondary	Metabolic Response Rate		At time of surgery - Average 3 months
Secondary	Post operative complication		One month after surgery