Colorectal Cancer
Conditions
Brief summary
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
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.
Interventions
DRUGCetuximab
anti-EGFR monoclonal antibody
DRUGmFOLFOX6
Oxaliplatin+LV5FU2
DRUGFOLFIRI
Irinotecan+LV5FU2
Sponsors
Chinese PLA General Hospital
Xiangya Hospital of Central South University
West China Hospital
Tongji Hospital
Ruijin Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival 1 (PFS1) | 4 months | from randomization to progression |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival 2 (PFS2) | 10 months | from signing informed consent to progression |
| Overall Survival (OS) | 24 months | from signing informed consent to death |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | 24 months | drug related toxicity from signing informed consent to death |
| Quality of life (QoL) | 24 months | QoL from signing informed consent to death |
Contacts
Primary ContactJun Zhang, MD & Ph. D
Backup ContactMin Shi, MD & Ph. D
Outcome results
None listed