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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Merck, S.L., Spain
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01450319
First received: October 7, 2011
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer (CRC)
Drug: Cetuximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Clinical Study of Cetuximab in Refractory Colorectal Cancer With K-RAS Mutated and Favourable FcγR IIa (CD32) Genotype

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Overall Survival (OS) time [ Time Frame: Time from randomization to death, reported between day of first subject randomized up to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of subjects with disease control according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1) [ Time Frame: Randomization until progressive disease reported between day of first subject randomized, up to 2 years ] [ Designated as safety issue: No ]
  • Progression Free Survival (PFS) time [ Time Frame: Time from randomization to progressive disease, reported between day of first subject randomized, up to 2 years ] [ Designated as safety issue: No ]
  • Number of subjects with Adverse Events [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
  • Number of FCγR IIa polymorphisms [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Correlation between Codon 12 and 13 mutations and rest of K-RAS mutations, with OS time and response to cetuximab treatment [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Correlation between genotype of Killer Inhibitory Receptors (KIR) and its ligands, with OS time and response to cetuximab treatment [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Correlation between Beta 2-microglobulin evolution, with OS time and response to cetuximab treatment [ Time Frame: Baseline up to 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 72
Study Start Date: September 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cetuximab 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.
Other Name: Erbitux

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 FcγRIIa-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 FcγRIIa (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
  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: NCT01450319

Locations
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, Spain
Sponsors and Collaborators
Merck KGaA
Merck, S.L., Spain
Investigators
Study Director: Medical Director Merck, S.L., Spain
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01450319     History of Changes
Other Study ID Numbers: EMR 062202-529, 2010-023580-18
Study First Received: October 7, 2011
Last Updated: March 6, 2014
Health Authority: Spain: Spanish Agency of Medicines
Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Merck KGaA:
K-RAS
FcγRII/IIIa genotypes
CRC
Colorectal cancer

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