Perioperative Chemotherapy With Bevacizumab for Colorectal Carcinomatosis French Part of the Main Bev-IP Study

Phase 2

Withdrawn

• Conditions: Colorectal Carcinomatosis
• Interventions: Procedure: Cytoreductive surgery combined with HIPEC; Drug: bevacizumab and HIPEC (Oxaliplatin 360 mg/m2).

• Registration Number: NCT03161041
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

Selected patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) benefit from cytoreductive surgery (CRS) combined with intraperitoneal chemoperfusion (IPC). However, even after optimal cytoreduction, systemic and locoregional recurrence are common. Perioperative chemotherapy with bevacizumab (BEV) may improve the outcome of these patients. The BEV-IP study is a phase II, single-arm, open-label study aimed at patients with colorectal or appendiceal adenocarcinoma with synchronous or metachronous PC. This study evaluates whether perioperative chemotherapy including BEV in combination with CRS and oxaliplatin-based IPC results in acceptable morbidity and mortality (primary composite endpoint). Secondary endpoints are treatment completion rate, chemotherapy-related toxicity, pathological response, progression free survival, and overall survival.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-05-18
• Study First Submitted QC: 2017-05-18
• Study First Posted: 2017-05-19
• Study Start: 2018-09-21
• Status Verified: 2018-11
• Primary Completion: 2018-11-13
• Study Completion: 2018-11-13
• Last Update Submitted: 2018-11-13
• Last Update Posted: 2018-11-14

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• biopsy proven adenocarcinoma of the colon or rectum and synchronous or metachronous peritoneal carcinomatosis.
• absence of systemic disease, with the exception of small, superficial liver metastases, requiring only minor surgery.
• resectable disease at staging, during laparoscopic evaluation and during exploration for cytoreductive surgery and intraperitoneal chemotherapy.
• complete macroscopic cytoreduction at the time of surgery (CC-0/1)
• good general health status (Karnofsky index > 70%)
• expected life expectancy more than 6 months
• no other malignancy than disease under study
• serum creatinine < 1.5 mg/dl or a calculated GFR ≥ 60 mL/min/1.73 m2
• serum total bilirubin < 1.5 mg/dl
• platelet count > 100,000/ml
• hemoglobin > 9g/dl
• neutrophil granulocytes > 1,500/ml
• International Normalized Ration (INR) 2 or < 2
• Absence of alcohol and/or drug abuse
• No inclusion in other clinical trials interfering with the study protocol
• No concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol
• Absence of heart failure (NYHA 2 or > 2) or significant coronary artery disease
• No pregnancy or breast feeding
• Adequate contraception in fertile patients

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Exclusion Criteria

• No written informed consent
• Tumour in the presence of obstruction
• Evidence of extra-abdominal disease or extensive liver metastasis
• Peritoneal cancer index > 25
• Active bacterial, viral or fungal infection
• Active gastro-duodenal ulcer
• Parenchymal liver disease (any stage cirrhosis)
• Uncontrolled diabetes mellitus
• Severe obstructive or restrictive respiratory insufficiency
• Psychiatric pathology capable of affecting comprehension and judgment faculty
• Known allergy to oxaliplatin.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bevacizumab and CRS with oxaliplatin	bevacizumab and HIPEC (Oxaliplatin 360 mg/m2).	Perioperative chemotherapy plus bevacizumab and CRS with oxaliplatin
Bevacizumab and CRS with oxaliplatin	Cytoreductive surgery combined with HIPEC	Perioperative chemotherapy plus bevacizumab and CRS with oxaliplatin

Primary Outcome Measures

Name	Time	Method
Number of participants with treatment related Adverse events grade IIIb or higher grade as assessed by Dindo-Clavien classification	Until 3 months after surgery and intraperitoneal chemotherapy	Major morbidity (grade IIIb or higher grade complication according to Dindo-Clavien classification)

Secondary Outcome Measures

Name	Time	Method
Overall survival	24 months after finishing the adjuvant chemotherapy	calculated from date of surgery until death
Pathological gross response of peritoneal tumour deposits to neoadjuvant combination chemotherapy with bevacizumab	Day 1 after termination of the cytoreductive surgery	Scored with a 3 level regression scale
Number of participants with treatement related Adverse events less than grade IIIb as assessed by Dindo-Clavien classification	Until 3 months after surgery and intraperitoneal chemotherapy	Minor morbidity (less than grade IIIb complication according to Dindo-Clavien classification).
Potential chemotherapy related morbidity	During the first 60 postoperative days	Adverse events will be described using MedDRA terms (version 18.0) and graded according to Common Terminology Criteria for Adverse Events (CTCAE version 5.0)
Quality of life assessment	24 months after finishing the adjuvant chemotherapy	Using SF 36 questionnaires
Treatment completion rate	Day 1 after termination of adjuvant chemotherapy	Percentage of patients receiving all planned courses
Progression free survival	24 months after finishing the adjuvant chemotherapy	Time interval between date of surgery and disease progression or death