Clinical trial NCT01161316: Safety and Efficacy Study of mFOLFOX-6 Plus Cetuximab for 8 Cycles Followed by mFOLFOX-6 Plus Cetuximab or Single Agent Cetuximab as Maintenance Therapy in Patients With Metastatic Colorectal Cancer and WT KRAS Tumours
Official title: Phase-II, Randomized, Multicentre Pilot Study to Evaluate the Safety and Efficacy of the Treatment With mFOLFOX-6 Plus Cetuximab Versus Initial Treatment With mFOLFOX-6 Plus Cetuximab (for 8 Cycles), Followed by Maintenance With Cetuximab Alone as First-line Treatment in Patients With Metastatic Colorectal Cancer (mCRC) and Wild-type KRAS Tumours
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: metastatic colorectal cancer
wild-type KRAS tumours
cetuximab
mFOLFOX-6
Lead sponsor: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Sponsor class: OTHER
First posted: 2010-07-13
Enrollment: 194
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the efficacy and safety of the combination of mFOLFOX-6 plus cetuximab for 8 cycles followed by mFOLFOX-6 plus cetuximab or single agent (s/a) cetuximab as maintenance therapy in patients (pts) with metastatic colorectal cancer (mCRC).


Eligibility criteria: Inclusion Criteria:

* Written informed consent.
* Patients of an age ≥ 18 years and \< 71
* Patients with an ECOG performance status ≤ 2
* Confirmed histological diagnosis of colorectal carcinoma with metastatic disease and wild-type KRAS.
* Presence of at least one target lesion that is measurable one-dimensionally (not located in an irradiated region).
* Life expectancy greater than 12 weeks.
* First evidence of chemotherapy-naïve metastatic disease. Adjuvant chemotherapy is allowed if it has been more than 6 months since the treatment was finished and there have been no signs of disease progression, neither during treatment nor during the 6 months following its completion.
* Adequate medullar reserve:
* Absolute neutrophil count ≥ 1.5 x 109/L
* Platelet count ≥ 100 x 109/L
* Haemoglobin ≥ 9 g/dL
* Adequate renal function: Creatinine clearance \> 30 mL/min, calculated using the Cockroff-Gault formula, or a serum creatinine \< 2 mg/dL or 177 umol/L
* An adequate liver function: ASAT (SGOT) and ALAT (SGPT) ≤ 2.5 x ULN (≤ 5 x ULN if there are liver metastases). Total bilirubin \< 1.5 x ULN. Alkaline phosphatase ≤ 2.5 x ULN ( ≤ 5 x ULN in the case of liver metastases or ≤ 10 x ULN in the case of bone metastases)

Exclusion Criteria:

* To have received prior systemic treatment for the metastatic disease
* Diagnosis or suspicion of brain or leptomeningeal metastases
* Major surgery or radiotherapy (except for antalgic surgery that does not include measurable target lesions) during the 4 weeks prior to inclusion in the study.
* Previous administration of monoclonal antibodies, agents inhibiting EGFR signal transduction or EGFR-targeted treatment.
* Participation in another clinical trial with drugs within the previous 30 days.
* Neoplasm in the 2 years prior to entering the study, except for non-melanoma skin carcinoma or in situ cervix carcinoma.
* Evidence of previous acute hypersensitivity reaction of any degree to any of the treatment's components.
* Clinically relevant peripheral neuropathy.
* Signs and symptoms, at the moment of entering the study, of acute or subacute bowel obstruction.
* A history of an acute episode of ischemic heart disease (angina or acute myocardial infarction) within the previous 12 months or an elevated risk of heart failure decompensation or uncontrolled arrhythmia.
* Serious active infection, including active tuberculosis and HIV diagnosis.
* Chronic immunological or hormonal treatment, except for hormone replacement treatment at physiological doses.
* Known drug or alcohol abuse.
* Legal incapacity or limited legal capacity.
* Pregnancy or breastfeeding. Premenopausal women must have a negative pregnancy test in urine or blood before entering the trial. Patients and their partners must take contraceptive measures (hormonal, barrier, or abstinence) if the possibility of conception exists, during the study and for 3 months after the end of the treatment thereof.
* Any geographical or social circumstance or any medical or psychological alteration that, in the investigator's opinion, will not allow the patient to conclude the study.

Primary outcomes:
measure: progression-free survival
timeFrame: 2010-2014
Secondary outcomes:
measure: overall survival
timeFrame: 2010-2014
measure: rate of objective responses
timeFrame: 2010-2014
measure: disease's resectability (R0)
timeFrame: 2010-2014
measure: evaluate hypomagnesaemia as a predictive factor in the treatment's efficacy
timeFrame: 2010-2014
measure: Adverse events
timeFrame: 2010-2014
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Spanish Cooperative Group for Gastrointestinal Tumour Therapy
Study officials:
affiliation: Hospital Reina Sofia. Córdoba. Spain
name: Enrique Aranda
role: STUDY_CHAIR
affiliation: Hospital Clínico San Carlos. Madrid. Spain
name: Eduardo Díaz-Rubio
role: STUDY_CHAIR
References:
citation: Benavides M, Diaz-Rubio E, Carrato A, Abad A, Guillen C, Garcia-Alfonso P, Gil S, Cano MT, Safont MJ, Gravalos C, Manzano JL, Sanchez A, Alcaide J, Lopez R, Massuti B, Sastre J, Martinez E, Escudero P, Mendez M, Aranda E. Tumour location and efficacy of first-line EGFR inhibitors in KRAS/RAS wild-type metastatic colorectal cancer: retrospective analyses of two phase II randomised Spanish TTD trials. ESMO Open. 2019 Dec 1;4(6):e000599. doi: 10.1136/esmoopen-2019-000599. eCollection 2019.
citation: Aranda E, Garcia-Alfonso P, Benavides M, Sanchez Ruiz A, Guillen-Ponce C, Safont MJ, Alcaide J, Gomez A, Lopez R, Manzano JL, Mendez Urena M, Sastre J, Rivera F, Gravalos C, Garcia T, Martin-Valades JI, Falco E, Navalon M, Gonzalez Flores E, Ma Garcia Tapiador A, Ma Lopez Munoz A, Barrajon E, Reboredo M, Garcia Teijido P, Viudez A, Cardenas N, Diaz-Rubio E; Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD). First-line mFOLFOX plus cetuximab followed by mFOLFOX plus cetuximab or single-agent cetuximab as maintenance therapy in patients with metastatic colorectal cancer: Phase II randomised MACRO2 TTD study. Eur J Cancer. 2018 Sep;101:263-272. doi: 10.1016/j.ejca.2018.06.024. Epub 2018 Jul 24.