History of Changes for Study: 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 (MACRO-2)

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Study Record Versions

Version	Submitted Date	Changes
1	July 12, 2010	None (earliest Version on record)
2	February 14, 2011	Recruitment Status, Study Status and Contacts/Locations
3	May 25, 2011	Study Status
4	February 6, 2012	Sponsor/Collaborators and Study Status
5	February 19, 2013	Recruitment Status, Study Status and Contacts/Locations
6	March 26, 2014	Study Status
7	March 23, 2015	Study Status and Study Design
8	July 24, 2015	Recruitment Status, Study Status and Study Design

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	TTD-09-04
Brief Title:	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 (MACRO-2)
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
Secondary IDs:	2009-017194-38 [EudraCT Number]

Study Status


Record Verification:	July 2010
Overall Status:	Not yet recruiting
Study Start:	July 2010
Primary Completion:	July 2014 [Anticipated]
Study Completion:	July 2014 [Anticipated]

First Submitted:	July 12, 2010
First Submitted that Met QC Criteria:	July 12, 2010
First Posted:	July 13, 2010 [Estimate]

Last Update Submitted that Met QC Criteria:	July 12, 2010
Last Update Posted:	July 13, 2010 [Estimate]

Sponsor/Collaborators


Sponsor:	Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Responsible Party:
Collaborators:

Oversight


U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring:	No

Study Description


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).
Detailed Description:

Conditions


Conditions:	Metastatic Colorectal Cancer
Keywords:	metastatic colorectal cancer wild-type KRAS tumours cetuximab mFOLFOX-6

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 2
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	None (Open Label)
Allocation:	Randomized
Enrollment:	192 [Anticipated]

Arms and Interventions

Arms

Assigned Interventions

Active Comparator: Control

mFOLFOX-6 + cetuximab until disease progression or early withdrawal.

Drug: mFOLFOX-6 + cetuximab until disease progression or early withdrawal.

Treatment regimen:

mFOLFOX-6, day 1, every two weeks; OXALIPLATIN 85 mg/m2; FOLINIC ACID 400 mg/m2; 5-FU 400 mg/m2 IV bolus; 5-FU 2400 mg/m2 continuous infusion for 46 hours

Cetuximab weekly. Cetuximab 400 mg/m2 the first time the treatment is administered; 250 mg/m2 for subsequent administrations.

Experimental: Experimental

8 cycles of mFOLFOX-6 + cetuximab, followed by cetuximab alone until disease progression or early withdrawal.

Drug: 8 cycles of mFOLFOX-6 + cetuximab, followed by cetuximab alone until disease progression or early withdrawal.

Treatment regimen.

mFOLFOX-6. day 1 every two weeks. OXALIPLATIN 85 mg/m2; FOLINIC ACID 400 mg/m2; 5-FU 400 mg/m2 IV bolus; 5-FU 2400 mg/m2 continuous infusion for 46 hours

Cetuximab weekly. Cetuximab 400 mg/m2 the first time the treatment is administered; 250 mg/m2 for subsequent administrations.

Outcome Measures


Primary Outcome Measures:
1.	progression-free survival [ Time Frame: 2010-2014 ]
Secondary Outcome Measures:
1.	overall survival [ Time Frame: 2010-2014 ]
2.	rate of objective responses [ Time Frame: 2010-2014 ]
3.	disease's resectability (R0) [ Time Frame: 2010-2014 ]
4.	evaluate hypomagnesaemia as a predictive factor in the treatment's efficacy [ Time Frame: 2010-2014 ]
5.	Adverse events [ Time Frame: 2010-2014 ]

Eligibility


Minimum Age:	18 Years
Maximum Age:	70 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
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.

Contacts/Locations


Study Officials:	Enrique Aranda Study Chair Hospital Reina Sofia. Córdoba. Spain
	Eduardo Díaz-Rubio Study Chair Hospital Clínico San Carlos. Madrid. Spain
Locations:	Spain
	Spanish Cooperative Group for Gastrointestinal Tumour Therapy Madrid, Spain, 28046 Contact:Contact: Inmaculada Ruiz de Mena, phD 0034913788275 ttd@ttdgroup.org

IPDSharing


Plan to Share IPD:

References


Links:	URL: http://www.ttdgroup.org Description: Related Info
Available IPD/Information: