Preoperative Systemic Therapy for Colorectal Cancer Peritoneal Metastases

Preoperative Systemic Therapy With FOLFOXIRI Plus Bevacizumab Followed by Cytoreductive Surgery Versus Upfront Cytoreductive Surgery for Resectable Colorectal Peritoneal Metastases: A Randomized Phase 2 Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Neoplasms; Colorectal Cancer; Peritoneal Neoplasms; Colorectal Cancer Metastatic; Chemotherapy Effect; Cytoreductive Surgery; Peritoneal Cancer; Peritoneal Metastases; Hyperthermic Intraperitoneal Chemotherapy
• Intervention / Treatment: Drug: Preoperative systematic therapy; Procedure: CRS+HIPEC; Drug: Postoperative chemotherapy; Drug: Postoperative chemotherapy

• Study Type: Interventional
• Enrollment (Anticipated): 168
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hui Wang, MD; Phone Number: +86-13926424886; Email: wang89@mail.sysu.edu.cn
• Study Contact Backup: Name: Huaiming Wang; Email: wanghm@mail.ssysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510655
      • Sixth Affiliated Hospital of Sun Yat-sen University
      • Contact: Hui Wang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chemotherapy group; 6 cycles of mFOLFOXIRI±Bev is followed by cytoreductive surgery. Postoperative 6 cycles of mFOLFOX is scheduled.	Drug: Preoperative 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.; Procedure: CRS+HIPEC; CRS+HIPEC aims to achieve CC0/CC1 resection. Oxaliplatin or mitomycin C is determined by the treating physician.; Drug: Postoperative chemotherapy; 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.; Drug: Postoperative chemotherapy; 12 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.
Active Comparator: Upfront surgery group; Upfront surgery group is followed by 12 cycles of mFOLFOX+Bev	Procedure: CRS+HIPEC; CRS+HIPEC aims to achieve CC0/CC1 resection. Oxaliplatin or mitomycin C is determined by the treating physician.; Drug: Postoperative chemotherapy; 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.; Drug: Postoperative chemotherapy; 12 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	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.	Up to five years after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response to preoperative systematic therapy	Assessed by tumor regression grade	About 4 months after randomization
Major adverse events of systematic therapy	Grade ≥3 adverse events by CTCAE 5.0	Up to 8 months after randomization
Overall survival	From randomization to death of any cause	Up to five years after randomization
Intraoperative peritoneal cancer index	Peritoneal cancer index (PCI) is a tool which sum scores in thirteen abdominal regions according to tumor size.	About 4 months after randomization
Complete cytoreductive surgery	R0/R1 resection or CC0/CC1 resection	About 4 months after randomization
Hospitalization time	Safety of cytoreductive surgery	About 4 months after randomization

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2022
• Primary Completion (Anticipated): July 1, 2025
• Study Completion (Anticipated): July 1, 2025

Study Registration Dates

• First Submitted: April 22, 2022
• First Submitted That Met QC Criteria: April 28, 2022
• First Posted (Actual): April 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 29, 2022
• Last Update Submitted That Met QC Criteria: April 28, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Site; Peritoneal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Abdominal Neoplasms; Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis; Peritoneal Neoplasms
• Other Study ID Numbers: STUCS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Participant-level raw data will not publically available unless reasonable request.

Drug and device information, study documents

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