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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-023580-18 | EudraCT Number |
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| Name | Class |
|---|---|
| Merck, S.L., Spain | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cetuximab | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Subjects With Disease Control Rate (DCR) | 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 |
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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 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (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:
Adequate hepatic and renal function, defined as:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck, S.L., Spain | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | A Coruña | Spain | ||||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33833048 | Derived | 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. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
MITT analysis set included all the subjects who received study drug treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Overall Survival (OS) Time | Overall survival was defined as the time from date of informed consent signature until death. | MITT analysis set included all the subjects who received study drug treatment. | Posted | Median | 95% Confidence Interval | Months | From the date of informed consent signature until death, assessed up to 3 years |
|
|
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
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cholestaticjaundice | Hepatobiliary disorders | MedDRA version 15.1. | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rash | Skin and subcutaneous tissue disorders | MedDRA version 15.1. | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck KGaA | +49-6151-72-5200 | service@merckgroup.com |
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| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| D000068818 | Cetuximab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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|
| From the date of informed consent signature until progressive disease, assessed up to 3 years |
| Progression Free Survival (PFS) Time | 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. | 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 | 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. | 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 | 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. | Baseline |
| Overall Survival (OS) Related to Codon G13D | 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). | 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) |
| Overall Survival (OS) Related to Killer Inhibitory Receptors 2DS4 (KIR2DS4) Functional Receptor (f/d) and Non-functional Receptor (NFR) | 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). | 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) |
| Beta 2-microglobulin | Baseline, Week 8 |
| Asturias |
| Spain |
| Research Site | Barcelona | Spain |
| Research Site | Córdoba | Spain |
| Research Site | Madrid | Spain |
| Research Site | Navarra | Spain |
| Research Site | Santiago de Compostela | Spain |
| Research Site | Seville | Spain |
| Research Site | Valencia | Spain |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Secondary | Percentage of Subjects With Disease Control Rate (DCR) | 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 | MITT analysis set included all the subjects who received study drug treatment. | Posted | Number | Percentage of subjects | From the date of informed consent signature until progressive disease, assessed up to 3 years |
|
|
|
| Secondary | Progression Free Survival (PFS) Time | 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. | MITT analysis set included all the subjects who received study drug treatment. | Posted | Median | 95% Confidence Interval | Months | From the date of informed consent signature until progressive disease (PD) or death, assessed up to 3 years |
|
|
|
| Secondary | Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, AEs Leading to Death | 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. | Safety analysis set included all the subjects who received at least one dose of the study drug treatment. | Posted | Number | Subjects | From the date of enrollment up to 30 days after the last dose of study drug administration, assessed up to 3 years |
|
|
|
| Secondary | Number of Subjects With Fcγ Receptors (FCγR) IIa/IIIa Polymorphisms | 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. | MITT analysis set included all the subjects who received study drug treatment. Subjects may fall into more than one category. | Posted | Number | Subjects | Baseline |
|
|
|
| Secondary | Overall Survival (OS) Related to Codon G13D | 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). | 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. | Posted | Median | 95% Confidence Interval | months | 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) |
|
|
|
| Secondary | Overall Survival (OS) Related to Killer Inhibitory Receptors 2DS4 (KIR2DS4) Functional Receptor (f/d) and Non-functional Receptor (NFR) | 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). | 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. | Posted | Median | 95% Confidence Interval | months | 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) |
|
|
|
| Secondary | Beta 2-microglobulin | MITT analysis set included all the subjects who received study drug treatment. Here "n" signifies number of evaluable subjects for each category, as specified. | Posted | Mean | Standard Deviation | microgram per milliliter (mcg/mL) | Baseline, Week 8 |
|
|
|
| 17 |
| 70 |
| 69 |
| 70 |
| Acute cholecystitis | Hepatobiliary disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Cholangitis | Hepatobiliary disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Liver failure | Hepatobiliary disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| General malaise | General disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Catheter point infection | Infections and infestations | MedDRA version 15.1. | Non-systematic Assessment |
|
| Listeria meningitis | Infections and infestations | MedDRA version 15.1. | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA version 15.1. | Non-systematic Assessment |
|
| Anal abscess | Infections and infestations | MedDRA version 15.1. | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 15.1. | Non-systematic Assessment |
|
| Disease progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 15.1. | Non-systematic Assessment |
|
| Heart failure | Cardiac disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Bowel obstruction | Gastrointestinal disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Acute renal failure | Renal and urinary disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Spontaneous hematoma | Blood and lymphatic system disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Pathologic fracture | Musculoskeletal and connective tissue disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Skin toxicity | Skin and subcutaneous tissue disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Catarrh | Respiratory, thoracic and mediastinal disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
| Jaundice | Hepatobiliary disorders | MedDRA version 15.1. | Non-systematic Assessment |
|
Not provided
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| Title | Measurements |
|---|---|
|
| AEs leading to death |
|
| Title | Measurements |
|---|---|
|
| FcγRIIIa: F/F |
|
| FcγRIIIa: F/V |
|