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

Sponsor

Fudan University (Other)

Overall Status

Completed

CT.gov ID

NCT01307878

Collaborator

Second Affiliated Hospital, School of Medicine, Zhejiang University (Other), Ruijin Hospital (Other), Changhai Hospital (Other)

320

Enrollment

Location

Arms

108

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Neoplasms Neoplasm Metastasis Liver Neoplasms Chemotherapy; Maternal, Affecting Fetus	Drug: chemotherapy ± targeted therapy	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

320 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Jun 1, 2021

Actual Study Completion Date :

Jun 1, 2021

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Progression-free survival [Up to 3 years]
Time from randomization to the date of disease progression or to death of any cause

Secondary Outcome Measures

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