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

Study Overview
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Brief Summary
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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.

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

Conditions
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Colorectal Carcinomatosis

Intervention / Treatment
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* Procedure: Cytoreductive surgery combined with HIPEC
* Drug: bevacizumab and HIPEC (Oxaliplatin 360 mg/m2).


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab and CRS with oxaliplatin<br>Perioperative chemotherapy plus bevacizumab and CRS with oxaliplatin | Procedure: Cytoreductive surgery combined with HIPEC<br>* Procedure/Surgery: Cytoreductive surgery combined with HIPEC (Oxaliplatin 360 mg/m2).<br>Drug: bevacizumab and HIPEC (Oxaliplatin 360 mg/m2).<br>* bevacizumab and HIPEC (Oxaliplatin 360 mg/m2).<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cytoreductive surgery, HIPEC, perioperative chemotherapy, peritoneal carcinomatosis, bevacizumab, colorectal surgery