Perioperative Chemotherapy With Bevacizumab for Colorectal Carcinomatosis

Study Overview
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Brief Summary
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The Bev-IP trial is designed to assess the feasibility and efficacy of a combined treatment consisting of perioperative combination chemotherapy with the vascular endothelial growth factor A inhibitor bevacizumab and cytoreductive surgery with intraperitoneal oxaliplatin.

Official Title
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BEV-IP: Perioperative Chemotherapy With Bevacizumab in Patients Undergoing Cytoreduction and Intraperitoneal Chemoperfusion for Colorectal Carcinomatosis

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Drug: perioperative chemotherapy plus bevacizumab
* Procedure: cytoreductive surgery
* Drug: Intraperitoneal Oxaliplatin


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 m 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

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 | Drug: perioperative chemotherapy plus bevacizumab<br>* preoperative and postoperative combination chemotherapy with bevacizumab<br>Procedure: cytoreductive surgery<br>* complete or nearly complete removal of synchronous or metachronous peritoneal carcinomatosis from CRC.<br>Drug: Intraperitoneal Oxaliplatin<br>* Pump-driven intraperitoneal administration of oxaliplatin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| surgical morbidity and mortality | This will be estimated with the Dindo-Clavien classification | until 3 months after surgery and intraperitoneal chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival | time interval between date of surgery and disease progression or death | 24 months after finishing the adjuvant chemotherapy | 
| overall survival | calculated from date of surgery until death | 24 months after finishing the adjuvant chemotherapy | 
| treatment completion rate | percentage of patients receiving all planned courses | day 1 after termination of adjuvant chemotherapy | 
| chemotherapy-related toxicity | percentage of patients experiencing chemotherapy-related toxicity will be assessed using the Common Terminology Criteria for Adverse Events (NCI-CTCAE) scoring system | 1 month after termination of the adjuvant chemotherapy | 
| pathological gross response of peritoneal tumour deposits to neoadjuvant combination chemotherapy with bevacizumab | will be scored with a 3 level regression scale | day 1 after termination of the cytoreductive surgery | 

 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