Colorectal Carcinomatosis
Conditions
Keywords
Cytoreductive surgery, HIPEC, perioperative chemotherapy, peritoneal carcinomatosis, bevacizumab, colorectal surgery
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.
Interventions
Procedure/Surgery: Cytoreductive surgery combined with HIPEC (Oxaliplatin 360 mg/m2).
DRUGbevacizumab and HIPEC (Oxaliplatin 360 mg/m2).
bevacizumab and HIPEC (Oxaliplatin 360 mg/m2).
Sponsors
Hospices Civils de Lyon
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| Overall survival | 24 months after finishing the adjuvant chemotherapy | calculated from date of surgery until death |
| Progression free survival | 24 months after finishing the adjuvant chemotherapy | Time interval between date of surgery and disease progression or death |
| 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). |
| Quality of life assessment | 24 months after finishing the adjuvant chemotherapy | Using the EORTC QLQ-C30 questionnaires |
| Treatment completion rate | Day 1 after termination of adjuvant chemotherapy | Percentage of patients receiving all planned courses |
| 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 |
Outcome results
None listed