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)

• ClinicalTrials.gov Identifier: NCT01161316
• Recruitment Status: Completed
• First Posted: July 13, 2010
• Last Update Posted: July 27, 2015
• Sponsor: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
• Information provided by (Responsible Party): Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

Tracking Information

• First Submitted Date: July 12, 2010
• First Posted Date: July 13, 2010
• Last Update Posted Date: July 27, 2015
• Study Start Date: August 2010
• Actual Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 12, 2010): progression-free survival [ Time Frame: 2010-2014 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 12, 2010)

• overall survival [ Time Frame: 2010-2014 ]
• rate of objective responses [ Time Frame: 2010-2014 ]
• disease's resectability (R0) [ Time Frame: 2010-2014 ]
• evaluate hypomagnesaemia as a predictive factor in the treatment's efficacy [ Time Frame: 2010-2014 ]
• Adverse events [ Time Frame: 2010-2014 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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
• 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: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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.

• 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.

Study Arms

• Active Comparator: Control
  mFOLFOX-6 + cetuximab until disease progression or early withdrawal.
  Intervention: Drug: mFOLFOX-6 + cetuximab until disease progression or early withdrawal.
• Experimental: Experimental
  8 cycles of mFOLFOX-6 + cetuximab, followed by cetuximab alone until disease progression or early withdrawal.
  Intervention: Drug: 8 cycles of mFOLFOX-6 + cetuximab, followed by cetuximab alone until disease progression or early withdrawal.

Publications *

• 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. Erratum In: ESMO Open. 2020 Jan;5(1):
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 23, 2015): 194
• Original Estimated Enrollment (submitted: July 12, 2010): 192
• Actual Study Completion Date: June 2015
• Actual Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT01161316
• Other Study ID Numbers: TTD-09-04; 2009-017194-38 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
• Original Responsible Party: Spanish Cooperative Group for Gastrointestinal Tumour Therapy
• Current Study Sponsor: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Enrique Aranda; Hospital Reina Sofia. Córdoba. Spain
• Study Chair: Eduardo Díaz-Rubio; Hospital Clínico San Carlos. Madrid. Spain

• PRS Account: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
• Verification Date: July 2015