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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Colorectal Neoplasms, Neoplasm Metastasis, Liver Neoplasms, Chemotherapy; Maternal, Affecting Fetus

Intervention / Treatment
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* Drug: chemotherapy ± targeted therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: arm A<br>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<br>* Chemotherapy regimen with either mFOLFOX6 plus cetuximab, bevacizumab or mFOLFOX6 alone were allocated, according the RAS genotype and patient affordability.<br>* Other names: chemotherapy plus targeted therapy;|
| No Intervention: arm B<br>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?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Unresectable colorectal liver metastases, Pre-operation chemotherapy, Primary tumor resection, Survival