A Phase 2 Clinical Study of Cetuximab in Refractory Colorectal Cancer With K-RAS Mutated and Favorable FcγRIIa (CD32) Genotype

Colorectal Cancer (CRC) Clinical Trial

— MUTEX  

Official title:

Phase II Clinical Study of Cetuximab in Refractory Colorectal Cancer With K-RAS Mutated and Favourable FcγR IIa (CD32) Genotype

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01450319
• Other study ID #: EMR 062202-529
• Secondary ID: 2010-023580-18
• Status: Completed
• Phase: Phase 2
• First received: October 7, 2011
• Last updated: June 3, 2015
• Start date: September 2011
• Est. completion date: December 2014

Study information

• Verified date: June 2015
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of MedicinesSpain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial Summary

This national, multicenter, open-label Phase 2 study without any control arm aims to evaluate the activity of cetuximab monotherapy in the treatment of refractory colorectal cancer in subjects with K-RAS mutated and FcγRIIa polymorphism tumors, in which there is no therapeutic alternative for treatment. Failure to standard treatment must be documented in these subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent form signed by the subject

• Age greater than or equal to (>=) 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (=<) 2

• Life expectancy of greater than 2 months

• Histological confirmed colorectal cancer (CRC) with mutated K-RAS and favorable genotypes (any H in Fc?RIIa-131). Selection will be done only based on Cluster of differentiation (CD)32 polymorphisms

• Epidermal growth factor receptor (EGFR) expression in his/her tumor sample

• Stage 4 metastatic disease, with at least one measurable lesion according to RECIST v1.1 criteria, documented within 28 days prior to the study inclusion

• Tumor tissue sample available for the assessment of K-RAS status and Fc?RIIa (CD32) genotype

• Subject who has received at least 2 prior therapeutic lines

• Adequate bone marrow function, defined as:

• hemoglobin greater than (>) 9.0 gram per deciliter (g/dL)

• platelet count >100 * 10^9 per liter (/L)

• absolute neutrophil count (ANC) >=1.5 * 10^9/L

• Adequate hepatic and renal function, defined as:

• Serum bilirubin =<1.5 times the upper limit of normal (ULN)

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =<2.5 * ULN in absence of liver metastasis and ALT and AST =<5 * ULN in the presence of liver metastasis

• Alkaline phosphatase =<2.5 * ULN or =<5 in the presence of liver metastasis or =<10 in the absence of liver metastasis

• Creatinine clearance >= 50 milliliter per minute (ml/min) (according to Cockcroft and Gault formula) or serum creatinine <1.5 * ULN

• Adequate recovery after recent surgery, chemotherapy or radiotherapy. Prior major surgery, chemotherapy, treatment with an investigational product or radiotherapy must have occurred at least 4 weeks before study inclusion

• Women of child-bearing potential must have a negative pregnancy test performed within 7 days prior to the study inclusion. Postmenopausal women must be amenorrheic for at least 12 months. If the risk of conception exists both male and female subjects must use effective contraception (for example, abstinence, intrauterine device (IUD), oral contraceptive, double barrier method or to be surgically sterile) since the signature of the consent form until at least 6 months after the end of treatment or end of last dose, whichever occurs first

Exclusion Criteria:

• Previous treatment with monoclonal antibodies against EGFR

• Toxicity, due to previous treatment, not resolved to Grade 1 before the subject's inclusion into the study

• Clinically relevant coronary disease or myocardial infarction, unstable angina, Grade >=2 congestive cardiac insufficiency according to New York Heart Association (NYHA) within 6 months before starting the study treatment

• Clinically significant vascular disease (for example, aortic aneurysm which requires surgery, pulmonary embolism, recent peripheral arterial thrombosis) within 12 months prior to starting the study treatment

• Evidence of uncontrolled brain metastases

• History of active neurological disease

• History of uncontrolled seizures

• History of lung fibrosis, acute pulmonary damage or interstitial pneumonia

• Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C infection, or presence of severe, uncontrolled intercurrent infections or other severe uncontrolled concomitant diseases

• Current Grade >=2 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE]) infection

• History of uncontrolled diabetes, uncontrolled hypertension or hepatic involvement

• Known or suspected allergy or hypersensitivity to cetuximab

• History of previous malignancy other than CRC occurring within 5 years before starting the study treatment, except for previously cured basal cell carcinoma of skin or carcinoma in situ of the cervix or urinary bladder treated more than 2 years before recruitment

• Participation in another treatment study with an investigational drug within the last 30 days

• Pregnancy or lactation

• Any medical, psychological, psychiatric or social uncontrolled problem which may interfere in the participation of the subject in the study or in the evaluation of the study results

• Psychological, familiar or geographic conditions not allowing the adequate follow-up and adherence to the study protocol

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer (CRC)
• Colorectal Neoplasms

Intervention

Drug:
• Cetuximab
Cetuximab will be administered intravenously at a dose of 500 milligram per square meter (mg/m^2) every alternate week until disease progression, death, or consent withdrawal.

Locations

Country	Name	City	State
Spain	Research Site	A Coruña
Spain	Research Site	Asturias
Spain	Research Site	Barcelona
Spain	Research Site	Cordoba
Spain	Research Site	Madrid
Spain	Research Site	Navarra
Spain	Research Site	Santiago de Compostela
Spain	Research Site	Sevilla
Spain	Research Site	Valencia

Sponsors (2)

Lead Sponsor	Collaborator
Merck KGaA	Merck, S.L., Spain

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) time		Time from randomization to death, reported between day of first subject randomized up to 2 years	No
Secondary	Percentage of subjects with disease control according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1)		Randomization until progressive disease reported between day of first subject randomized, up to 2 years	No
Secondary	Progression Free Survival (PFS) time		Time from randomization to progressive disease, reported between day of first subject randomized, up to 2 years	No
Secondary	Number of subjects with Adverse Events		Up to 2 years	Yes
Secondary	Number of FC?R IIa polymorphisms		Baseline	No
Secondary	Correlation between Codon 12 and 13 mutations and rest of K-RAS mutations, with OS time and response to cetuximab treatment		Up to 2 years	No
Secondary	Correlation between genotype of Killer Inhibitory Receptors (KIR) and its ligands, with OS time and response to cetuximab treatment		Up to 2 years	No
Secondary	Correlation between Beta 2-microglobulin evolution, with OS time and response to cetuximab treatment		Baseline up to 8 weeks	No