Trial Outcomes & Findings for Cetuximab in Refractory Colorectal Cancer With K-RAS Mutated and Favorable FcγRIIa (CD32) Genotype (NCT NCT01450319)

NCT ID: NCT01450319

Last Updated: 2016-11-28

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 73 participants
• Primary outcome timeframe: From the date of informed consent signature until death, assessed up to 3 years
• Results posted on: 2016-11-28

Participant Flow

A total of 73 subjects were enrolled in the trial. Out of 73 subjects, 70 subjects received the study drug and start the study and three subjects were excluded from the modified intent-to-treat (MITT) analysis set.

Participant milestones

Measure	Cetuximab Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) every 2 weeks until disease progression, death, or consent withdrawal.
Overall Study STARTED	70
Overall Study COMPLETED	70
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Cetuximab n=70 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) every 2 weeks until disease progression, death, or consent withdrawal.
Age, Continuous	63.61 Years STANDARD_DEVIATION 10.54 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants

PRIMARY outcome

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

Population: MITT analysis set included all the subjects who received study drug treatment.

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

Outcome measures

Measure	Cetuximab n=70 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) every 2 weeks until disease progression, death, or consent withdrawal.
Overall Survival (OS) Time	6.71 Months Interval 5.42 to 8.05

SECONDARY outcome

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

Population: MITT analysis set included all the subjects who received study drug treatment.

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

Outcome measures

Measure	Cetuximab n=70 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) every 2 weeks until disease progression, death, or consent withdrawal.
Percentage of Subjects With Disease Control Rate (DCR)	22.86 Percentage of subjects

SECONDARY outcome

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

Population: MITT analysis set included all the subjects who received study drug treatment.

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.

Outcome measures

Measure	Cetuximab n=70 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) every 2 weeks until disease progression, death, or consent withdrawal.
Progression Free Survival (PFS) Time	2.53 Months Interval 2.43 to 2.7

SECONDARY outcome

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

Population: Safety analysis set included all the subjects who received at least one dose of the study drug treatment.

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.

Outcome measures

Measure	Cetuximab n=70 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) every 2 weeks until disease progression, death, or consent withdrawal.
Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, AEs Leading to Death AEs	69 Subjects
Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, AEs Leading to Death SAEs	17 Subjects
Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, AEs Leading to Death AEs leading to discontinuation	2 Subjects
Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, AEs Leading to Death AEs leading to death	3 Subjects

SECONDARY outcome

Timeframe: Baseline

Population: MITT analysis set included all the subjects who received study drug treatment. Subjects may fall into more than one category.

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.

Outcome measures

Measure	Cetuximab n=70 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) every 2 weeks until disease progression, death, or consent withdrawal.
Number of Subjects With Fcγ Receptors (FCγR) IIa/IIIa Polymorphisms FcγRIIa: H/H	27 Subjects
Number of Subjects With Fcγ Receptors (FCγR) IIa/IIIa Polymorphisms FcγRIIa: R/H	43 Subjects
Number of Subjects With Fcγ Receptors (FCγR) IIa/IIIa Polymorphisms FcγRIIIa: V/V	6 Subjects
Number of Subjects With Fcγ Receptors (FCγR) IIa/IIIa Polymorphisms FcγRIIIa: F/F	28 Subjects
Number of Subjects With Fcγ Receptors (FCγR) IIa/IIIa Polymorphisms FcγRIIIa: F/V	36 Subjects

SECONDARY outcome

Timeframe: 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)

Population: MITT analysis set included all the subjects who received study drug treatment. Here "Number of subjects analyzed" signifies total number of evaluable subjects for this outcome measure; "n" signifies number of evaluable subjects for each category, as specified.

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).

Outcome measures

Measure	Cetuximab n=62 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) every 2 weeks until disease progression, death, or consent withdrawal.
Overall Survival (OS) Related to Codon G13D G13D (n=14)	7.2 months Interval 4.8 to Data could not be evaluated due to lack of events.
Overall Survival (OS) Related to Codon G13D No G13D (n=48)	6.3 months Interval 4.8 to 7.9

SECONDARY outcome

Timeframe: 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)

Population: MITT analysis set included all the subjects who received study drug treatment. Here "Number of subjects analyzed" signifies number of evaluable subjects for this outcome measure.

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).

Outcome measures

Measure	Cetuximab n=66 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) every 2 weeks until disease progression, death, or consent withdrawal.
Overall Survival (OS) Related to Killer Inhibitory Receptors 2DS4 (KIR2DS4) Functional Receptor (f/d) and Non-functional Receptor (NFR) f/d (n=10)	4.8 months Interval 2.2 to 7.3
Overall Survival (OS) Related to Killer Inhibitory Receptors 2DS4 (KIR2DS4) Functional Receptor (f/d) and Non-functional Receptor (NFR) NFR (n=56)	7.4 months Interval 6.0 to 8.4

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: MITT analysis set included all the subjects who received study drug treatment. Here "n" signifies number of evaluable subjects for each category, as specified.

Outcome measures

Measure	Cetuximab n=70 Participants Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) every 2 weeks until disease progression, death, or consent withdrawal.
Beta 2-microglobulin Baseline (n=61)	2.35 microgram per milliliter (mcg/mL) Standard Deviation 0.58
Beta 2-microglobulin Week 8 (n=29)	2.37 microgram per milliliter (mcg/mL) Standard Deviation 1.13

Adverse Events

Cetuximab

Serious events: 17 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cetuximab n=70 participants at risk Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) every 2 weeks until disease progression, death, or consent withdrawal.
Hepatobiliary disorders Cholestaticjaundice	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Hepatobiliary disorders Acute cholecystitis	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Hepatobiliary disorders Cholangitis	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Hepatobiliary disorders Liver failure	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
General disorders Pyrexia	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
General disorders Pain	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
General disorders General malaise	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Infections and infestations Catheter point infection	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Infections and infestations Listeria meningitis	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Infections and infestations Urinary tract infection	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Infections and infestations Anal abscess	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Disease progression	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Cardiac disorders Heart failure	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Gastrointestinal disorders Bowel obstruction	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Metabolism and nutrition disorders Hypocalcemia	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Renal and urinary disorders Acute renal failure	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Blood and lymphatic system disorders Spontaneous hematoma	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Musculoskeletal and connective tissue disorders Pathologic fracture	1.4% 1/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years

Other adverse events

Measure	Cetuximab n=70 participants at risk Cetuximab was administered intravenously at a dose of 500 milligram per square meter (mg/m\^2) every 2 weeks until disease progression, death, or consent withdrawal.
Skin and subcutaneous tissue disorders Rash	55.7% 39/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Skin and subcutaneous tissue disorders Skin toxicity	11.4% 8/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Skin and subcutaneous tissue disorders Pruritus	11.4% 8/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Skin and subcutaneous tissue disorders Skin fissures	11.4% 8/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Skin and subcutaneous tissue disorders Dermatitis	11.4% 8/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Skin and subcutaneous tissue disorders Acne	10.0% 7/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Skin and subcutaneous tissue disorders Dry skin	8.6% 6/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
General disorders Asthenia	45.7% 32/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
General disorders Mucosal inflammation	14.3% 10/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
General disorders Pyrexia	14.3% 10/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
General disorders Oedema peripheral	8.6% 6/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
General disorders Pain	7.1% 5/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Gastrointestinal disorders Constipation	21.4% 15/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Gastrointestinal disorders Nausea	17.1% 12/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Gastrointestinal disorders Vomiting	15.7% 11/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Gastrointestinal disorders Abdominal pain	12.9% 9/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Gastrointestinal disorders Abdominal pain upper	11.4% 8/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Gastrointestinal disorders Dry mouth	10.0% 7/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Gastrointestinal disorders Diarrhoea	8.6% 6/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Metabolism and nutrition disorders Decreased appetite	22.9% 16/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Metabolism and nutrition disorders Hypomagnesaemia	12.9% 9/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.4% 8/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Respiratory, thoracic and mediastinal disorders Cough	10.0% 7/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Respiratory, thoracic and mediastinal disorders Epistaxis	5.7% 4/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Respiratory, thoracic and mediastinal disorders Catarrh	5.7% 4/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Musculoskeletal and connective tissue disorders Back pain	14.3% 10/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Musculoskeletal and connective tissue disorders Arthralgia	7.1% 5/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Blood and lymphatic system disorders Anaemia	12.9% 9/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Psychiatric disorders Insomnia	7.1% 5/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years
Hepatobiliary disorders Jaundice	5.7% 4/70 • AEs with onset from the date of enrollment up to 30 days after the last dose of study drug administration; assessed up to 3 years

Additional Information

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Merck KGaA

Phone: +49-6151-72-5200

Email: service@merckgroup.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER