Colorectal Neoplasms, Colorectal Cancer, Colorectal Cancer Metastatic, Peritoneal Metastases, Peritoneal Cancer, Peritoneal Neoplasms, Chemotherapy Effect, Cytoreductive Surgery, Hyperthermic Intraperitoneal Chemotherapy
Conditions
Brief summary
This is an open-label, parallel-group, phase 2 randomized trial which randomizes patients with isolated resectable colorectal cancer peritoneal metastases to receive preoperative systematic therapy followed by CRS+HIPEC and postoperative chemotherapy or upfront CRS+HIPEC followed by postoperative chemotherapy.
Interventions
DRUGPreoperative systematic therapy
6 cycles of mFOLFOXIRI±Bev is administrated before CRS+HIPEC. Irinotecan165mg/m2 IV day 1, oxaliplatin 85mg/m2 IV day 1, leucovorin 400mg/m2 IV day , bevacizumab mg/kg IV day 1, 5-fluorouracil 400mg/m2, continuous infusion over 46-48h. Dose reduction is permitted. Bev will not be administrated in at the last two cycles for minimizing surgery complications.
PROCEDURECRS+HIPEC
CRS+HIPEC aims to achieve CC0/CC1 resection. Oxaliplatin or mitomycin C is determined by the treating physician.
6 cycles of mFOLFOX+Bev is administrated after CRS+HIPEC. Oxaliplatin 85mg/m2 IV day 1, leucovorin 400mg/m2 IV day , bevacizumab mg/kg IV day 1, 5-fluorouracil 400mg/m2 IV bolus day 1,5-fluorouracil 400mg/m2, continuous infusion over 46-48h. Dose reduction is permitted.
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; * Historically and radiologically confirmed colorectal cancer peritoneal metastasis except for appendical origin; * Tolerable to scheduled chemotherapy; * No evidence of extraperitoneal metastases at enrollment; * Resectable disease determined by radiological and laparoscopy/laparotomy; * No systematic therapy within 6 months before enrollment; * Tolerable to cytoreductive surgery.
Exclusion criteria
* Without adequate organ function (e.g. :neutrophil countt≤1.5×10\^9/L, or platelets≤75×10\^12/L，or hemoglobin\<90g/L, or aminotransferase、aspartate aminotransferaseAST\<2.5ULN, or total bilirubin\<1.5ULN, or creatinine\<1.5ULN; * Emergency surgery; * Recent thromboembolic event or cerebrovascular disease (12 months before enrollment); * Pregnancy or lactation * Comorbid with severe physical or mental disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | Up to five years after randomization | From randomization to progression by RECIST1.1, or appearance of measurable lesion after non-measureable lesion, or intraoperative unresectable disease, or recurrence after surgery, or death from any reason. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response to preoperative systematic therapy | About 4 months after randomization | Assessed by tumor regression grade |
| Major adverse events of systematic therapy | Up to 8 months after randomization | Grade ≥3 adverse events by CTCAE 5.0 |
| Hospitalization time | About 4 months after randomization | Safety of cytoreductive surgery |
| Intraoperative peritoneal cancer index | About 4 months after randomization | Peritoneal cancer index (PCI) is a tool which sum scores in thirteen abdominal regions according to tumor size. |
| Complete cytoreductive surgery | About 4 months after randomization | R0/R1 resection or CC0/CC1 resection |
| Overall survival | Up to five years after randomization | From randomization to death of any cause |
Countries
China
Contacts
Primary ContactHui Wang, MD
Backup ContactHuaiming Wang
Outcome results
None listed