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

NCT01161316 | Completed Phase 2

• 2 other identifiers: TTD-09-042009-017194-38
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 1

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).

Conditions

Metastatic Colorectal Cancer

Keywords

metastatic colorectal cancer; wild-type KRAS tumours; cetuximab; mFOLFOX-6

Outcome Measures

Primary Outcomes (1)

• progression-free survival

  2010-2014

Secondary Outcomes (5)

• overall survival

  2010-2014

• rate of objective responses

  2010-2014

• disease's resectability (R0)

  2010-2014

• evaluate hypomagnesaemia as a predictive factor in the treatment's efficacy

  2010-2014

• Adverse events

  2010-2014

Study Arms (2)

Control

ACTIVE COMPARATOR

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

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.

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

Interventions

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

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.

Control

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

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

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• To have received prior systemic treatment for the metastatic disease
• Diagnosis or suspicion of brain or leptomeningeal metastases
• 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.

Sponsors & Collaborators

• Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD): lead

Study Sites (1)

Spanish Cooperative Group for Gastrointestinal Tumour Therapy

Madrid, 28046, Spain

Location

Related Publications (2)

• 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.

  PMID: 31803504 DERIVED

• 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.

  PMID: 30054049 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Enrique Aranda

  Hospital Reina Sofia. Córdoba. Spain

  STUDY CHAIR

• Eduardo Díaz-Rubio

  Hospital Clínico San Carlos. Madrid. Spain

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2010
• First Posted: July 13, 2010
• Study Start: August 1, 2010
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: July 27, 2015

Record last verified: 2015-07

Locations

ES (1)