Cetuximab in Refractory Colorectal Cancer With K-RAS Mutated and Favorable FcγRIIa (CD32) Genotype

NCT01450319 | Completed Phase 2 Results

• 2 other identifiers: EMR 062202-5292010-023580-18
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 9

Brief 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 of the first and second line conventional therapeutic lines was documented.

Conditions

Colorectal Neoplasms

Keywords

K-RAS; FcγRII/IIIa genotypes; CRC; Colorectal cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS) Time

  Overall survival was defined as the time from date of informed consent signature until death.

  From the date of informed consent signature until death, assessed up to 3 years

Secondary Outcomes (7)

• Percentage of Subjects With Disease Control Rate (DCR)

  From the date of informed consent signature until progressive disease, assessed up to 3 years

• Progression Free Survival (PFS) Time

  From the date of informed consent signature until progressive disease (PD) or death, assessed up to 3 years

• Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, AEs Leading to Death

  From the date of enrollment up to 30 days after the last dose of study drug administration, assessed up to 3 years

• Number of Subjects With Fcγ Receptors (FCγR) IIa/IIIa Polymorphisms

  Baseline

• Overall Survival (OS) Related to Codon G13D

  From the date of informed consent signature until death, lost-to-follow-up or end of study, whatever occurred first (maximal up to 3 years)

Study Arms (1)

Cetuximab

EXPERIMENTAL

Drug: Cetuximab

Interventions

Cetuximab DRUG

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

Also known as: Erbitux

Cetuximab

Eligibility Criteria

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

You may qualify if:

• 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
• 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:
• haemoglobin \> 9.0 gram per deciliter (g/dL)
• platelet count \>100\*10\^9 per liter
• absolute neutrophil count (ANC) \>=1.5\*10\^9/Liter
• 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

You may not qualify if:

• Previous treatment with monoclonal antibodies against EGFR
• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead
• Merck, S.L., Spain: collaborator

Study Sites (9)

Research Site

A Coruña, Spain

Location

Research Site

Asturias, Spain

Location

Research Site

Barcelona, Spain

Location

Research Site

Córdoba, Spain

Location

Research Site

Madrid, Spain

Location

Research Site

Navarra, Spain

Location

Research Site

Santiago de Compostela, Spain

Location

Research Site

Seville, Spain

Location

Research Site

Valencia, Spain

Location

Related Publications (1)

• Manzanares-Martin B, Cebrian Aranda A, Del Puerto-Nevado L, Gonzalez R, Solanes S, Gomez-Espana MA, Garcia-Foncillas J, Aranda E. Improving selection of patients with metastatic colorectal cancer to benefit from cetuximab based on KIR genotypes. J Immunother Cancer. 2021 Apr;9(4):e001705. doi: 10.1136/jitc-2020-001705.

  PMID: 33833048 DERIVED

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

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Director

  Merck, S.L., Spain

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2011
• First Posted: October 12, 2011
• Study Start: December 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: November 28, 2016
• Results First Posted: June 15, 2016

Record last verified: 2016-10

Locations

ES (9)