New Adjuvant Chemotherapy of Asymptomatic Resectable Primary Lesion With Unresectable Liver-limited Metastases

Pre-operation Chemotherapy of Primary Tumor Resection for Colorectal Cancer Patients With Asymptomatic Resectable Primary Lesion and Synchronous Unresectable Liver-limited Metastases

To evaluate the survival benefit of pre-operation chemotherapy of primary tumor tesection (PTR) compared upfront PTR for colorectal cancer (CRC) patients with an asymptomatic resectable primary tumor and synchronous unresectable liver-limited metastases with conversion therapy intent.

Study Overview

• Status: Completed
• Conditions: Neoplasm Metastasis; Liver Neoplasms; Colorectal Neoplasms; Chemotherapy; Maternal, Affecting Fetus
• Intervention / Treatment: Drug: chemotherapy ± targeted therapy

Detailed Description

Fast recovery with fewer postoperative complications, prevention of potential tumor-related complications during chemotherapy, life quality improvement, and also can alleviate the tumor load of patients, are some advantages of PTR that may play a role in improving cancer-specific survival. However, it should be pointed out that nearly all the retrospective and prospective studies for the beneficial of PTR enrolled more multi-organ metastases mCRC patients, and with palliative treatment purpose. As for unresectable colorectal liver-limited metastases (CRLMs) with good Eastern Cooperative Oncology Group performance status (ECOG PS), the primary objective is to make metastases resectable by high-intensity conversion therapy and achieved a state of no-evidence of disease. PTR were preferred performed before enrollment in some related RCT studies, including the CELIM study, CAIRO and CAIRO2 studies. Pooled-analysis of our two RCT studies, PTR pre or post chemotherapy for these unresectable liver-limited metastases patients had less morbidities and no mortalities, but no RCTs have focused on survival benefit of pre-operation chemotherapy of PTR for unresectable CRLMs.

• Study Type: Interventional
• Enrollment (Actual): 320
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age between 18 - 75 years old
• colorectal adenocarcinoma pathologically
• without any chemotherapy or radiotherapy
• unresectable liver metastasis and without other metastasis
• resectable colorectal cancer
• suitable for chemotherapy
• agreed by patients

Exclusion Criteria:

• age below 18 years old or greater than 75 years old
• haven't pathological diagnosis of colorectal adenocarcinoma
• with any chemotherapy or radiotherapy
• resectable liver metastasis or without other metastasis
• unresectable colorectal cancer
• unsuitable for chemotherapy
• not agreed by patients

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: arm A; Pre-PTR, chemotherapy regimen with either mFOLFOX6 plus cetuximab, bevacizumab or mFOLFOX6 alone were allocated, according the RAS genotype and patient affordability.	Drug: chemotherapy ± targeted therapy; Chemotherapy regimen with either mFOLFOX6 plus cetuximab, bevacizumab or mFOLFOX6 alone were allocated, according the RAS genotype and patient affordability.; Other Names: chemotherapy plus targeted therapy
No Intervention: arm B; Upfront PTR, then chemotherapy regimen with either mFOLFOX6 plus cetuximab, bevacizumab or mFOLFOX6 alone were allocated, according the RAS genotype and patient affordability.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Time from randomization to the date of disease progression or to death of any cause	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time from randomization to death from any cause or the date of the last follow-up	Up to 3 years
Tumor response	Response according to RECIST 1.1	Up to 6 months
Secondary resection rate Second radical resectability	The rate of patients converted to resection for liver metastases	Up to 6 months
Surgical complications	The proportion of patients with any complications occurred within 30 days after surgery	30 days after surgery
Toxicity of chemotherapy	Patients will be evaluated for Adverse Events at the start of each treatment cycle according to NCI CTC 3.0 criteria	Up to 6 months

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Changhai Hospital; Second Affiliated Hospital, School of Medicine, Zhejiang University; Ruijin Hospital
• Investigators: Study Chair: Jianmin Xu, Ph.D., M.D, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2012
• Primary Completion (Actual): June 1, 2021
• Study Completion (Actual): June 1, 2021

Study Registration Dates

• First Submitted: March 2, 2011
• First Submitted That Met QC Criteria: March 2, 2011
• First Posted (Estimate): March 3, 2011

Study Record Updates

• Last Update Posted (Actual): June 14, 2022
• Last Update Submitted That Met QC Criteria: June 12, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Survival; Primary tumor resection; Unresectable colorectal liver metastases; Pre-operation chemotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Liver Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis; Liver Neoplasms
• Other Study ID Numbers: RECUT