Cetuximab in Refractory Colorectal Cancer With K-RAS Mutated and Favorable FcγRIIa (CD32) Genotype (MUTEX)
|ClinicalTrials.gov Identifier: NCT01450319|
Recruitment Status : Completed
First Posted : October 12, 2011
Results First Posted : June 15, 2016
Last Update Posted : November 28, 2016
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Neoplasms||Drug: Cetuximab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||73 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Clinical Study of Cetuximab in Refractory Colorectal Cancer With K-RAS Mutated and Favourable FcγR IIa (CD32) Genotype|
|Study Start Date :||December 2011|
|Primary Completion Date :||December 2014|
|Study Completion Date :||December 2014|
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.
Other Name: Erbitux
- Overall Survival (OS) Time [ Time Frame: From the date of informed consent signature until death, assessed up to 3 years ]Overall survival was defined as the time from date of informed consent signature until death.
- Percentage of Subjects With Disease Control Rate (DCR) [ Time Frame: From the date of informed consent signature until progressive disease, assessed up to 3 years ]DCR was defined as those subjects achieving complete response (CR), partial response (PR) or stable disease (SD), according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1). For target lesions (TLs), CR was defined as the disappearance of all TLs; PR was defined as at least a 30 percent (%) decrease in the sum of longest diameter (SLD) of the TLs, taking as a reference the baseline (BL) SLD; Stable disease (SD) was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD; and PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For non-target lesions (NTLs), CR was defined as the disappearance of all NTLs and normalization of tumor marker levels; SD was defined as the persistence of 1 or more NTLs and/or maintenance of tumor marker levels above normal limits; and progressive disease (PD) was defined as the appearance
- Progression Free Survival (PFS) Time [ Time Frame: From the date of informed consent signature until progressive disease (PD) or death, assessed up to 3 years ]PFS was defined as the time from informed consent signature until PD or death, whatever occurred first. Subjects who did not have disease progression or were lost to follow-up, were censored at the date of last contact, known to be alive and progression free; moreover, those subjects who started a new treatment (different from cetuximab), were censored at the date of starting the new treatment. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from BL or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
- Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, AEs Leading to Death [ Time Frame: From the date of enrollment up to 30 days after the last dose of study drug administration, assessed up to 3 years ]An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
- Number of Subjects With Fcγ Receptors (FCγR) IIa/IIIa Polymorphisms [ Time Frame: Baseline ]The antibody fragment C portion (FCy) of cetuximab interacts with Fc-gamma receptors (FCyRs) expressed by immune effector cells. Polymorphisms were described in genes coding for FCyRIIa and in FCyRIIIa. A histidine/arginine polymorphism at position 131 for FCyRIIa gene and valine ⁄ phenylalanine polymorphism at position 158 for the FCyRIIIa gene were reported to be functionally relevant in the ADCC mechanism. All subjects were analyzed and classified as carriers of every different polymorphism of FCy Receptors: for FCyRIIa (H/H, homozygous alleles with histidine and R/H, heterozygous alleles with arginine/histidine) and FCyRIIIa (V/V, homozygous alleles with valine, F/F, homozygous alleles with phenylalanine and F/V, heterozygous alleles with valine ⁄ phenylalanine) (units: subjects with every type of polymorphism) .The FCyR genotype was determined using a TaqMan Allelic Discrimination Assay.
- Overall Survival (OS) Related to Codon G13D [ Time Frame: 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) ]OS was defined as the time from informed consent signature until death. Subjects without death were censored at the last date known alive (within the study).
- Overall Survival (OS) Related to Killer Inhibitory Receptors 2DS4 (KIR2DS4) Functional Receptor (f/d) and Non-functional Receptor (NFR) [ Time Frame: From the date of informed consent signature until death, lost-to-follow-up or end of study, whatever occurred first (maximal assessed up to 3 years) ]OS was defined as the time from informed consent signature until death. Subjects without death were censored at the last date known alive (within the study).
- Beta 2-microglobulin [ Time Frame: Baseline, Week 8 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01450319
|A Coruña, Spain|
|Santiago de Compostela, Spain|
|Study Director:||Medical Director||Merck, S.L., Spain|