Clinical trial NCT02942706: 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
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Colorectal Cancer
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: Chinese PLA General Hospital
name: Xiangya Hospital of Central South University
name: West China Hospital
name: Tongji Hospital
First posted: 2016-10-24
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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;

Primary outcomes:
measure: Progression Free Survival 1 (PFS1)
timeFrame: 4 months
Secondary outcomes:
measure: Progression Free Survival 2 (PFS2)
timeFrame: 10 months
measure: Overall Survival (OS)
timeFrame: 24 months
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 24 months
measure: Quality of life (QoL)
timeFrame: 24 months
Other outcomes:
Locations:
Study officials:
affiliation: Ruijin Hospital
name: Jun Zhang, MD & Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.