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)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Spanish Cooperative Group for Digestive Tumour Therapy (TTD)
ClinicalTrials.gov Identifier:
NCT01161316
First received: July 12, 2010
Last updated: March 26, 2014
Last verified: March 2014
  Purpose

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).


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: mFOLFOX-6 + cetuximab until disease progression or early withdrawal.
Drug: 8 cycles of mFOLFOX-6 + cetuximab, followed by cetuximab alone until disease progression or early withdrawal.
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Spanish Cooperative Group for Digestive Tumour Therapy (TTD):

Primary Outcome Measures:
  • progression-free survival [ Time Frame: 2010-2014 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • overall survival [ Time Frame: 2010-2014 ] [ Designated as safety issue: No ]
  • rate of objective responses [ Time Frame: 2010-2014 ] [ Designated as safety issue: No ]
  • disease's resectability (R0) [ Time Frame: 2010-2014 ] [ Designated as safety issue: No ]
  • evaluate hypomagnesaemia as a predictive factor in the treatment's efficacy [ Time Frame: 2010-2014 ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: 2010-2014 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 192
Study Start Date: August 2010
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
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.


  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
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 and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01161316

Locations
Spain
Spanish Cooperative Group for Gastrointestinal Tumour Therapy
Madrid, Spain, 28046
Sponsors and Collaborators
Spanish Cooperative Group for Digestive Tumour Therapy (TTD)
Investigators
Study Chair: Enrique Aranda Hospital Reina Sofia. Córdoba. Spain
Study Chair: Eduardo Díaz-Rubio Hospital Clínico San Carlos. Madrid. Spain
  More Information

Additional Information:
No publications provided

Responsible Party: Spanish Cooperative Group for Digestive Tumour Therapy (TTD)
ClinicalTrials.gov Identifier: NCT01161316     History of Changes
Other Study ID Numbers: TTD-09-04, 2009-017194-38
Study First Received: July 12, 2010
Last Updated: March 26, 2014
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Spanish Cooperative Group for Digestive Tumour Therapy (TTD):
metastatic colorectal cancer
wild-type KRAS tumours
cetuximab
mFOLFOX-6

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Cetuximab
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014