Cetuximab Maintenance Treatment Versus Continuation After Induction Therapy in mCRC

Study Overview
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Brief Summary
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This study is try to evaluate the effect of cetuximab monotherapy as maintenance treatment, versus continuation after 8 courses of induction therapy with cetuximab plus standard chemotherapy regimen (FOLFIRI or mFOLFOX6）in metastatic colorectal cancer (mCRC) patients. The maintenance treatments are continued until disease progression or untolerated toxicity. The aim of this study is to demonstrate that cetuximab monotherapy is non-inferior to continuation treatment, in those mCRC patients who responded to induction therapy(SD, PR, or CR), and carry biomarker-panels (KRAS, NRAS, BRAF, and PIK3CA) favor EGFR antibody.

Detailed Description
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This study is try to evaluate the effect of cetuximab monotherapy as maintenance treatment, versus continuation after 8 courses of induction therapy with cetuximab plus standard chemotherapy regimen (FOLFIRI or mFOLFOX6）in metastatic colorectal cancer (mCRC) patients. The maintenance treatments are continued until disease progression or untolerated toxicity. The aim of this study is to demonstrate that cetuximab monotherapy is non-inferior to continuation treatment, in those mCRC patients who responded to induction therapy(SD, PR, or CR), and carry biomarker-panels (KRAS, NRAS, BRAF, and PIK3CA) favor EGFR antibody. Furthermore, the mutation status of biomarker panel consist of KRAS, NRAS, HRAS, BRAF, EGFR, ERBB2, ERBB3, PIK3CA, PTEN, SMAD4, SMAD2, TGFBR2, cMET, Src, mTOR, VEGFR1, VEGFR2, EPHA2, MSI, TP53, ERCC1, ERCC5, KCNQ5, ILK, and Myc will be analyzed by NGS sequencing. The ctDNA as surrogate marker via liquid biopsy will be conducted before randomization, during maintenance treatment, and disease progression.

Official Title
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Biomarker-Panel Guided Maintenance Treatment With Cetuximab Monotherapy Versus Continuation After First Line Induction Therapy of Metastatic Colorectal Cancer (mCRC) : a Multicenter, Prospective, Randomized Controlled Trial

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Cetuximab
* Drug: mFOLFOX6
* Drug: FOLFIRI


Participation Criteria
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Eligibility Criteria
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Before the start of induction therapy: Inclusion Criteria: Histological proof of colorectal cancer (in case of a single metastasis, histological or cytological proof of this lesion should be obtained); Distant metastases which are either technically unresectable or no chance to reach NED (patients with only local recurrence are not eligible); Measurable disease (> 1 cm on spiral CT scan or > 2 cm on chest X-ray; liver ultrasound is not allowed). Serum CEA may not be used as a parameter for disease evaluation; Ongoing or planned first line induction therapy with 8 cycles of FOLFIRI or mFOLFOX6. Exclusion criteria Prior adjuvant treatment for stage II/III colorectal cancer ending within 6 months before the start of induction treatment Any prior adjuvant treatment after resection of distant metastases Previous systemic treatment for advanced disease RAS mutant mCRC At randomisation: Inclusion criteria: WHO performance status 0-1 (Karnofsky PS > 70%); Disease evaluation with proven SD, PR or CR according to RECIST after 8 cycles of FOLFIRI or mFOLFOX6; Laboratory values obtained ≤ 2 weeks prior to randomisation: adequate bone marrow function (Hb > 8.0 mmol/L, absolute neutrophil count > 1.5 x 109/L, platelets > 100 x 109/L), renal function (serum creatinine ≤ 1.5x ULN and creatinine clearance, Cockroft formula, > 30 ml/min), liver function (serum bilirubin ≤ 2 x ULN, serum transaminases ≤ 3 x ULN without presence of liver metastases or ≤ 5x ULN with presence of liver metastases); Life expectancy > 24 weeks; Age: 18-75 years; Negative pregnancy test in women with childbearing potential; Expected adequacy of follow-up; Institutional Review Board approval; Written informed consent Exclusion criteria Chronic active infection; Any other concurrent severe or uncontrolled disease preventing the safe administration of study drugs;

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: Cet maintenance<br>Cetuximab maintenance treatment following induction treatment | Drug: Cetuximab<br>* anti-EGFR monoclonal antibody<br>* Other names: Erbitux;|
| Active Comparator: Cet+chemo continuation<br>Cetuximab plus continuation mFOLFOX6/FOLFIRI regimens | Drug: Cetuximab<br>* anti-EGFR monoclonal antibody<br>* Other names: Erbitux;Drug: mFOLFOX6<br>* Oxaliplatin+LV5FU2<br>Drug: FOLFIRI<br>* Irinotecan+LV5FU2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival 1 (PFS1) | from randomization to progression | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival 2 (PFS2) | from signing informed consent to progression | 10 months | 
| Overall Survival (OS) | from signing informed consent to death | 24 months | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | drug related toxicity from signing informed consent to death | 24 months | 
| Quality of life (QoL) | QoL from signing informed consent to death | 24 months |