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

Perioperative Chemotherapy With Bevacizumab in Patients Undergoing Cytoreduction and Intraperitoneal Chemoperfusion for Colorectal Carcinomatosis - French Part of the Main Bev-IP Study

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.

Study Overview

• Status: Withdrawn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

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Bevacizumab and CRS with oxaliplatin; Perioperative chemotherapy plus bevacizumab and CRS with oxaliplatin	Procedure: Cytoreductive surgery combined with HIPEC; Procedure/Surgery: Cytoreductive surgery combined with HIPEC (Oxaliplatin 360 mg/m2).; Drug: bevacizumab and HIPEC (Oxaliplatin 360 mg/m2).; bevacizumab and HIPEC (Oxaliplatin 360 mg/m2).

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatement related Adverse events less than grade IIIb as assessed by Dindo-Clavien classification	Minor morbidity (less than grade IIIb complication according to Dindo-Clavien classification).	Until 3 months after surgery and intraperitoneal chemotherapy
Potential chemotherapy related morbidity	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)	During the first 60 postoperative days
Overall survival	calculated from date of surgery until death	24 months after finishing the adjuvant chemotherapy
Progression free survival	Time interval between date of surgery and disease progression or death	24 months after finishing the adjuvant chemotherapy
Pathological gross response of peritoneal tumour deposits to neoadjuvant combination chemotherapy with bevacizumab	Scored with a 3 level regression scale	Day 1 after termination of the cytoreductive surgery
Quality of life assessment	Using the EORTC QLQ-C30 questionnaires	24 months after finishing the adjuvant chemotherapy
Treatment completion rate	Percentage of patients receiving all planned courses	Day 1 after termination of adjuvant chemotherapy
Quality of life assessment	Using SF 36 questionnaires	24 months after finishing the adjuvant chemotherapy

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 21, 2018
• Primary Completion (ANTICIPATED): November 13, 2018
• Study Completion (ACTUAL): November 13, 2018

Study Registration Dates

• First Submitted: May 18, 2017
• First Submitted That Met QC Criteria: May 18, 2017
• First Posted (ACTUAL): May 19, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 14, 2018
• Last Update Submitted That Met QC Criteria: November 13, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Cytoreductive surgery, HIPEC, perioperative chemotherapy, peritoneal carcinomatosis, bevacizumab, colorectal surgery
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Oxaliplatin; Bevacizumab
• Other Study ID Numbers: 69HCL17_0239

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No