Preoperative Systemic Therapy for Colorectal Cancer Peritoneal Metastases

• Sponsor: Sun Yat-sen University (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05353582
• Collaborator: (none)
• Enrollment: 168
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 37
• Patients Per Site Per Month: 4.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Neoplasms; Colorectal Cancer; Colorectal Cancer Metastatic; Peritoneal Metastases; Peritoneal Cancer; Peritoneal Neoplasms; Chemotherapy Effect; Cytoreductive Surgery; Hyperthermic Intraperitoneal Chemotherapy	Drug: Preoperative systematic therapy; Procedure: CRS+HIPEC; Drug: Postoperative chemotherapy; Drug: Postoperative chemotherapy	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 168 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Anticipated Study Start Date: Jun 1, 2022
• Anticipated Primary Completion Date: Jul 1, 2025
• Anticipated Study Completion Date: Jul 1, 2025

Arms and Interventions

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.
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; 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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Response to preoperative systematic therapy [About 4 months after randomization]

   Assessed by tumor regression grade

2. Major adverse events of systematic therapy [Up to 8 months after randomization]

   Grade ≥3 adverse events by CTCAE 5.0

3. Overall survival [Up to five years after randomization]

   From randomization to death of any cause

4. 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.

5. Complete cytoreductive surgery [About 4 months after randomization]

   R0/R1 resection or CC0/CC1 resection

6. Hospitalization time [About 4 months after randomization]

   Safety of cytoreductive surgery

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sixth Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong	China	510655

Sponsors and Collaborators

• Sun Yat-sen University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Yanhong Deng, Director, Sun Yat-sen University
• ClinicalTrials.gov Identifier: NCT05353582
• Other Study ID Numbers: STUCS
• First Posted: Apr 29, 2022
• Last Update Posted: Apr 29, 2022
• Last Verified: Apr 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis; Peritoneal Neoplasms

Study Results

No Results Posted as of Apr 29, 2022