Cetuximab Maintenance Treatment Versus Continuation After Induction Therapy in mCRC

NCT ID: NCT02942706

Last Updated: 2021-04-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-30
• Study Completion Date: 2022-10-31

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cet maintenance

Cetuximab maintenance treatment following induction treatment

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: DRUG

anti-EGFR monoclonal antibody

Cet+chemo continuation

Cetuximab plus continuation mFOLFOX6/FOLFIRI regimens

Group Type: ACTIVE_COMPARATOR

Cetuximab

Intervention Type: DRUG

anti-EGFR monoclonal antibody

mFOLFOX6

Intervention Type: DRUG

Oxaliplatin+LV5FU2

FOLFIRI

Intervention Type: DRUG

Irinotecan+LV5FU2

Interventions

Cetuximab

anti-EGFR monoclonal antibody

Intervention Type: DRUG

mFOLFOX6

Oxaliplatin+LV5FU2

Intervention Type: DRUG

FOLFIRI

Irinotecan+LV5FU2

Intervention Type: DRUG

Other Intervention Names

Erbitux

Eligibility Criteria

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.

• 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;

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:

• Chronic active infection;
• Any other concurrent severe or uncontrolled disease preventing the safe administration of study drugs;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese PLA General Hospital

OTHER

Sponsor Role: collaborator

Xiangya Hospital of Central South University

OTHER

Sponsor Role: collaborator

West China Hospital

OTHER

Sponsor Role: collaborator

Tongji Hospital

OTHER

Sponsor Role: collaborator

Ruijin Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jun Zhang

MD & Ph. D, Professor of Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jun Zhang, MD & Ph.D

Role: PRINCIPAL_INVESTIGATOR

Ruijin Hospital

Central Contacts

Jun Zhang, MD & Ph. D

Role: CONTACT

junzhang10977@sjtu.edu.cn

+86-13818332497

Min Shi, MD & Ph. D

Role: CONTACT

shimin0412005@126.com

+86-13512118830

References

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.

Reference Type: BACKGROUND

PMID: 24703531 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22473155 (View on PubMed)

Other Identifiers

BLOC-1

Identifier Type: -

Identifier Source: org_study_id