Cetuximab Maintenance Treatment Versus Continuation After Induction Therapy in mCRC

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Cetuximab; Drug: mFOLFOX6; Drug: FOLFIRI

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.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Min Shi, MD & Ph. D; Phone Number: +86-13512118830; Email: shimin0412005@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cet maintenance; Cetuximab maintenance treatment following induction treatment	Drug: Cetuximab; anti-EGFR monoclonal antibody; Other Names: Erbitux
Active Comparator: Cet+chemo continuation; Cetuximab plus continuation mFOLFOX6/FOLFIRI regimens	Drug: Cetuximab; anti-EGFR monoclonal antibody; Other Names: Erbitux; Drug: mFOLFOX6; Oxaliplatin+LV5FU2; Drug: FOLFIRI; Irinotecan+LV5FU2

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Collaborators: Xiangya Hospital of Central South University; Chinese PLA General Hospital; West China Hospital; Tongji Hospital
• Investigators: Principal Investigator: Jun Zhang, MD & Ph.D, Ruijin Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2021
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: October 2, 2016
• First Submitted That Met QC Criteria: October 20, 2016
• First Posted (Estimate): October 24, 2016

Study Record Updates

• Last Update Posted (Actual): April 30, 2021
• Last Update Submitted That Met QC Criteria: April 29, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: BLOC-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No