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

Metastatic Colorectal Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01161316
• Other study ID #: TTD-09-04
• Secondary ID: 2009-017194-38
• Status: Completed
• Phase: Phase 2
• First received: July 12, 2010
• Last updated: July 24, 2015
• Start date: August 2010
• Est. completion date: June 2015

Study information

• Verified date: July 2015
• Source: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 194
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

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.
• 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.

Locations

Country	Name	City	State
Spain	Spanish Cooperative Group for Gastrointestinal Tumour Therapy	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression-free survival		2010-2014	No
Secondary	overall survival		2010-2014	No
Secondary	rate of objective responses		2010-2014	No
Secondary	disease's resectability (R0)		2010-2014	No
Secondary	evaluate hypomagnesaemia as a predictive factor in the treatment's efficacy		2010-2014	No
Secondary	Adverse events		2010-2014	Yes

External Links

•   Link