Back to resultsCetuximab Maintenance Treatment Versus Continuation After Induction Therapy in mCRC
Primary Purpose
Colorectal Cancer
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Cetuximab
mFOLFOX6
FOLFIRI
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility 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 Exclusion criteria
- Chronic active infection;
- Any other concurrent severe or uncontrolled disease preventing the safe administration of study drugs;
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Cet maintenance
Cet+chemo continuation
Arm Description
Cetuximab maintenance treatment following induction treatment
Cetuximab plus continuation mFOLFOX6/FOLFIRI regimens
Outcomes
Primary Outcome Measures
Progression Free Survival 1 (PFS1)
from randomization to progression
Secondary Outcome Measures
Progression Free Survival 2 (PFS2)
from signing informed consent to progression
Overall Survival (OS)
from signing informed consent to death
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
drug related toxicity from signing informed consent to death
Quality of life (QoL)
QoL from signing informed consent to death
Full Information
NCT ID
NCT02942706
First Posted
October 2, 2016
Last Updated
April 29, 2021
Sponsor
Ruijin Hospital
Collaborators
Chinese PLA General Hospital, Xiangya Hospital of Central South University, West China Hospital, Tongji Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02942706
Brief Title
Cetuximab Maintenance Treatment Versus Continuation After Induction Therapy in mCRC
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Unknown status
Study Start Date
November 2021 (Anticipated)
Primary Completion Date
October 2022 (Anticipated)
Study Completion Date
October 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ruijin Hospital
Collaborators
Chinese PLA General Hospital, Xiangya Hospital of Central South University, West China Hospital, Tongji Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cet maintenance
Arm Type
Experimental
Arm Description
Cetuximab maintenance treatment following induction treatment
Arm Title
Cet+chemo continuation
Arm Type
Active Comparator
Arm Description
Cetuximab plus continuation mFOLFOX6/FOLFIRI regimens
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
anti-EGFR monoclonal antibody
Intervention Type
Drug
Intervention Name(s)
mFOLFOX6
Intervention Description
Oxaliplatin+LV5FU2
Intervention Type
Drug
Intervention Name(s)
FOLFIRI
Intervention Description
Irinotecan+LV5FU2
Primary Outcome Measure Information:
Title
Progression Free Survival 1 (PFS1)
Description
from randomization to progression
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Progression Free Survival 2 (PFS2)
Description
from signing informed consent to progression
Time Frame
10 months
Title
Overall Survival (OS)
Description
from signing informed consent to death
Time Frame
24 months
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
drug related toxicity from signing informed consent to death
Time Frame
24 months
Title
Quality of life (QoL)
Description
QoL from signing informed consent to death
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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 Exclusion criteria
Chronic active infection;
Any other concurrent severe or uncontrolled disease preventing the safe administration of study drugs;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jun Zhang, MD & Ph. D
Phone
+86-13818332497
Email
junzhang10977@sjtu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Min Shi, MD & Ph. D
Phone
+86-13512118830
Email
shimin0412005@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jun Zhang, MD & Ph.D
Organizational Affiliation
Ruijin Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
24703531
Citation
Wasan H, Meade AM, Adams R, Wilson R, Pugh C, Fisher D, Sydes B, Madi A, Sizer B, Lowdell C, Middleton G, Butler R, Kaplan R, Maughan T; COIN-B investigators. Intermittent chemotherapy plus either intermittent or continuous cetuximab for first-line treatment of patients with KRAS wild-type advanced colorectal cancer (COIN-B): a randomised phase 2 trial. Lancet Oncol. 2014 May;15(6):631-9. doi: 10.1016/S1470-2045(14)70106-8. Epub 2014 Apr 3.
Results Reference
background
PubMed Identifier
22473155
Citation
Tveit KM, Guren T, Glimelius B, Pfeiffer P, Sorbye H, Pyrhonen S, Sigurdsson F, Kure E, Ikdahl T, Skovlund E, Fokstuen T, Hansen F, Hofsli E, Birkemeyer E, Johnsson A, Starkhammar H, Yilmaz MK, Keldsen N, Erdal AB, Dajani O, Dahl O, Christoffersen T. Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol. 2012 May 20;30(15):1755-62. doi: 10.1200/JCO.2011.38.0915. Epub 2012 Apr 2.
Results Reference
background
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Cetuximab Maintenance Treatment Versus Continuation After Induction Therapy in mCRC
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