Gastric Cancer
Conditions
Keywords
1st line treatment for Gastric Cancer, Cetuximab, Capecitabine, Xeloda, Cisplatin, Progression-free survival
Brief summary
The primary objective of this study is to demonstrate that addition of cetuximab to 1st-line treatment with capecitabine (Xeloda, X) and cisplatin (P) \[XP\] chemotherapy regimen has a clinically relevant benefit for subjects with advanced gastric adenocarcinoma including gastroesophageal junction (GEJ) adenocarcinoma, in terms of progression free survival (PFS). Secondary objectives are to assess cetuximab plus XP versus XP alone with respect to overall survival, overall tumor response, quality of life (QoL) and safety.
Interventions
DRUGCetuximab
Single first dose of cetuximab 400 milligram per square meter (mg/m\^2) will be administered intravenously over 120 minutes followed by weekly intravenous infusion of cetuximab 250 mg/m\^2 over 60 minutes in each 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.
DRUGCapecitabine
Capecitabine 1000 mg/m\^2 will be administered orally twice daily from evening of Day 1 to morning of Day 15 for every 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.
DRUGCisplatin
Cisplatin 80 mg/m\^2 will be administered intravenously with infusion over 1 to 4 hours on Day 1 of each 3-week treatment cycle, until documented disease progression, unacceptable toxicity, or withdrawal of consent.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent before any study-related activities are carried out * Age greater than or equal to (\>=) 18 years * Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (Adenocarcinoma of the gastroesophageal junction \[AEG\] Types I-III according to Siewert classification) * Archived tumor material sample for at least subsequent standardized Epidermal Growth Factor Receptor (EGFR) expression assessment * Unresectable advanced (M0) or unresectable metastatic (M1) disease * At least one radiographically documented measurable lesion in a previously non-irradiated area according to response evaluation criteria in solid tumors (RECIST). The primary tumor site is to be considered as a non-measurable lesion only * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Estimated life expectancy greater than (\>) 12 weeks * Medically accepted contraception (if the risk of conception exists) * Glomerular filtration rate (GFR) \>= 60 milliliter per minute (mL/min) The GFR is based on the Cockcroft-Gault formula for creatinine clearance * Aspartate-aminotransferase (ASAT) less than or equal to (=\<) 2.5 \* upper limit of normal (ULN) and alanine-aminotransferase (ALAT) =\< 2.5 \*ULN * Bilirubin =\< 3 \* ULN * Absolute neutrophil count (ANC) \>= 1.5 \* 10\^9 per liter * Platelets \>= 100 \* 10\^9 per liter * Hemoglobin \>=10 gram per deciliter (g/dL) (without transfusions) * Sodium and potassium within normal limits or =\< 10 percent above or below (supplementation permitted)
Exclusion criteria
* Prior chemotherapy, however, previous (neo-)adjuvant (radio-) chemotherapy allowed if finished \> 1 year prior to start of study treatment and no more than 300 mg/m\^2 cisplatin has been administered * Prior treatment with an antibody or molecule targeting EGFR and/or Vascular Endothelial Growth Factor Receptor (VEGFR) related signaling pathways * Brain metastasis and/or leptomeningeal disease (known or suspected) * Radiotherapy (except localized radiotherapy for pain relief), major surgery or any investigational drug within 30 days before the start of study treatment * Concurrent chronic systemic immune or hormone therapy not indicated in this study protocol (except for physiologic replacement) * Clinically relevant coronary artery disease (New York Heart Association \[NYHA\] functional angina classification III/IV), congestive heart failure (NYHA III/IV), clinically relevant cardiomyopathy, history of myocardial infarction in the 12 months before study Screening, or high risk of uncontrolled arrhythmia * Active Hepatitis B or C * Chronic diarrhea or short bowel syndrome * Presence of any contra-indication to treatment with cetuximab, capecitabine and cisplatin including: * Known hypersensitivity to capecitabine, fluorouracil, cisplatin, cetuximab or to any of the excipients of these drugs * Known dihydropyrimidine dehydrogenase (DPD) deficiency * Hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption * Current treatment with sorivudine or chemically related analogues, such as brivudine * Symptomatic peripheral neuropathy National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade \>= 2 and/or ototoxicity NCI CTCAE Grade \>= 2, except if due to trauma or mechanical impairment due to tumor mass * Pregnancy or lactation period * Concurrent treatment with a non-permitted drug * Treatment in another clinical study within 30 days prior to study screening * Previous malignancy other than gastric cancer within 5 years prior to study screening, except for basal cell cancer of the skin or pre-invasive cancer of the cervix * Medical or psychological conditions that would not permit the subject to complete the study or sign informed consent * Legal incapacity or limited legal capacity * Significant disease which, in the Investigator's opinion, would exclude the subject from the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Time: Independent Review Committee (IRC) Assessments | Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012) | The PFS time is defined as the duration from randomization to either first observation of progressive disease (PD) or occurrence of death due to any cause within 60 days of the last tumor assessment or randomization. Participants without event are censored on the date of last tumor assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Time from randomization to death or last day known to be alive, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date, (31 Mar 2012) | The OS time is defined as the time from randomization to death or last day known to be alive. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier. |
| Best Overall Response (BOR) Rate: Independent Review Committee (IRC) Assessments | Every 6 weeks until progression, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date, (31 Mar 2012) | The BOR rate is defined as the percentage of participants having achieved complete response (CR) or partial response (PR) as the best overall response, based on radiological assessments (based on response evaluation criteria in solid tumors \[RECIST\] Version 1.0) from the IRC. |
| Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Baseline, Week 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012) | Mean global health status and social functioning scores (EORTC QLQ-C30) against time for each treatment group. Scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation. Higher scores indicate a better QoL. |
| Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Baseline, Week 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012) | EQ-5D questionnaire is a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 single items are combined to obtain a single index score that is health utility index (HUI) score reflecting subject's preferences for different health states. The lowest possible score is -0.59 and the highest is 1.00, higher scores on the EQ-5D represent a better QoL. |
| Safety - Number of Participants With Adverse Events (AEs) | Time from first dose up to Day 30 after last dose of study treatment, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012) | An Adverse Event (AE) is defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to Baseline during a clinical study with an investigational medicinal product (IMP), regardless of causal relationship and even if no IMP has been administered. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Chile, China, Czechia, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Poland, Portugal, Romania, Russia, South Korea, Spain, Taiwan, United Kingdom
Participant flow
Recruitment details
First/last participant (informed consent): June 2008/December 2010. Clinical data cut-off: 31 March 2012 Study completion 17 February 2013.
Pre-assignment details
Enrolled: 1,191 screened for eligibility; 287 excluded (mainly non-fulfillment of inclusion or exclusion criteria). 904 participants randomized.
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab Plus Capecitabine Plus Cisplatin Cetuximab weekly (initial dose 400 milligram per square meter \[mg/m\^2\] followed by 250 mg/m\^2 intravenous infusion), cisplatin (3-week cycle, 80 mg/m\^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m\^2 orally twice daily for 14 days ) until documented disease progression, unacceptable toxicity, or withdrawal of consent. | 455 |
| Capecitabine Plus Cisplatin Cisplatin (3-week cycle, 80 mg/m\^2 intravenous infusion on Day 1) and capecitabine (3-week cycle, 1000 mg/m\^2 orally twice daily for 14 days) until documented disease progression, unacceptable toxicity, or withdrawal of consent. | 449 |
| Total | 904 |
Baseline characteristics
| Characteristic | Cetuximab Plus Capecitabine Plus Cisplatin | Capecitabine Plus Cisplatin | Total |
|---|---|---|---|
| Age, Continuous | 58.0 years STANDARD_DEVIATION 11.16 | 58.5 years STANDARD_DEVIATION 10.83 | 58.3 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 116 Participants | 115 Participants | 231 Participants |
| Sex: Female, Male Male | 339 Participants | 334 Participants | 673 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 441 / 446 | 429 / 436 |
| serious Total, serious adverse events | 239 / 446 | 194 / 436 |
Outcome results
Primary
Progression-free Survival (PFS) Time: Independent Review Committee (IRC) Assessments
The PFS time is defined as the duration from randomization to either first observation of progressive disease (PD) or occurrence of death due to any cause within 60 days of the last tumor assessment or randomization. Participants without event are censored on the date of last tumor assessment.
Time frame: Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012)
Population: Intent-to-treat (ITT) population included all participants who were randomized to trial treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab Plus Capecitabine Plus Cisplatin | Progression-free Survival (PFS) Time: Independent Review Committee (IRC) Assessments | 4.4 months |
| Capecitabine Plus Cisplatin | Progression-free Survival (PFS) Time: Independent Review Committee (IRC) Assessments | 5.6 months |
Comparison: Primary efficacy analysis: To test equality of progression free survival time between treatment groups, applying the two-sided stratified log-rank test (randomization strata: disease stage, previous oesophagectomy/gastrectomy and prior(neo-) adjuvant(radio) chemotherapy, α=5%).p-value: 0.315895% CI: [0.92, 1.292]Stratified log rank
Secondary
Best Overall Response (BOR) Rate: Independent Review Committee (IRC) Assessments
The BOR rate is defined as the percentage of participants having achieved complete response (CR) or partial response (PR) as the best overall response, based on radiological assessments (based on response evaluation criteria in solid tumors \[RECIST\] Version 1.0) from the IRC.
Time frame: Every 6 weeks until progression, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date, (31 Mar 2012)
Population: ITT population included all participants who were randomized to trial treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab Plus Capecitabine Plus Cisplatin | Best Overall Response (BOR) Rate: Independent Review Committee (IRC) Assessments | 29.9 percentage of participants |
| Capecitabine Plus Cisplatin | Best Overall Response (BOR) Rate: Independent Review Committee (IRC) Assessments | 29.2 percentage of participants |
Comparison: The best overall response rate was compared with the Cochran-Mantel-Haenszel test (strata: disease stage, previous oesophagectomy/gastrectomy and prior(neo-) adjuvant(radio) chemotherapy, two-sided with α=5%).p-value: 0.769695% CI: [0.7844, 1.3882]Cochran-Mantel-Haenszel
Secondary
Overall Survival (OS)
The OS time is defined as the time from randomization to death or last day known to be alive. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier.
Time frame: Time from randomization to death or last day known to be alive, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date, (31 Mar 2012)
Population: ITT population included all participants who were randomized to trial treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab Plus Capecitabine Plus Cisplatin | Overall Survival (OS) | 9.4 months |
| Capecitabine Plus Cisplatin | Overall Survival (OS) | 10.7 months |
Comparison: To test equality of OS time between treatment groups, applying the two-sided stratified log-rank test (randomization strata: disease stage, previous oesophagectomy/gastrectomy and prior (neo-) adjuvant(radio) chemotherapy, α=5%)p-value: 0.954795% CI: [0.866, 1.165]Stratified log rank
Secondary
Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Mean global health status and social functioning scores (EORTC QLQ-C30) against time for each treatment group. Scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation. Higher scores indicate a better QoL.
Time frame: Baseline, Week 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012)
Population: Analysis population included participants who had at least one evaluable EORTC QLQ-C30 questionnaire and were also included in the ITT population. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Baseline | 74.36 units on a scale | Standard Deviation 27.077 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 36 | 65.06 units on a scale | Standard Deviation 22.629 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 6 | 68.94 units on a scale | Standard Deviation 28.885 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 12 | 60.17 units on a scale | Standard Deviation 20.796 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 12 | 71.48 units on a scale | Standard Deviation 26.547 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 42 | 59.29 units on a scale | Standard Deviation 21.558 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 18 | 71.22 units on a scale | Standard Deviation 25.317 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 24 | 62.46 units on a scale | Standard Deviation 22.978 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 24 | 74.20 units on a scale | Standard Deviation 26.143 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 48 | 63.39 units on a scale | Standard Deviation 21.317 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 30 | 78.51 units on a scale | Standard Deviation 24.766 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 6 | 59.00 units on a scale | Standard Deviation 21.879 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 36 | 76.28 units on a scale | Standard Deviation 21.73 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 54 | 60.63 units on a scale | Standard Deviation 16.198 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 42 | 68.57 units on a scale | Standard Deviation 27.348 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 30 | 63.65 units on a scale | Standard Deviation 21.722 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status at Week 48 | 80.36 units on a scale | Standard Deviation 22.705 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 60 | 62.50 units on a scale | Standard Deviation 13.918 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 54 | 74.71 units on a scale | Standard Deviation 27.682 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 18 | 60.45 units on a scale | Standard Deviation 20.015 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 60 | 78.33 units on a scale | Standard Deviation 23.632 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Baseline | 57.49 units on a scale | Standard Deviation 22.168 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 60 | 68.06 units on a scale | Standard Deviation 32.144 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Baseline | 57.19 units on a scale | Standard Deviation 22.124 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 6 | 61.80 units on a scale | Standard Deviation 22.089 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 12 | 63.35 units on a scale | Standard Deviation 22.077 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 18 | 61.83 units on a scale | Standard Deviation 21.499 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 24 | 63.61 units on a scale | Standard Deviation 19.477 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 30 | 64.11 units on a scale | Standard Deviation 19.757 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 36 | 57.72 units on a scale | Standard Deviation 21.602 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 42 | 62.64 units on a scale | Standard Deviation 22.005 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 48 | 66.67 units on a scale | Standard Deviation 19.395 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 54 | 66.67 units on a scale | Standard Deviation 14.651 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Global health status: Week 60 | 61.81 units on a scale | Standard Deviation 17.21 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Baseline | 76.52 units on a scale | Standard Deviation 26.601 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 6 | 75.70 units on a scale | Standard Deviation 27.415 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 12 | 75.65 units on a scale | Standard Deviation 27.691 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 18 | 75.51 units on a scale | Standard Deviation 25.612 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 24 | 78.26 units on a scale | Standard Deviation 27.633 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 30 | 76.67 units on a scale | Standard Deviation 24.962 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 36 | 73.58 units on a scale | Standard Deviation 22.353 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 42 | 78.16 units on a scale | Standard Deviation 22.318 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status at Week 48 | 78.00 units on a scale | Standard Deviation 23.432 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Social functioning status: Week 54 | 80.56 units on a scale | Standard Deviation 27.371 |
Secondary
Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire
EQ-5D questionnaire is a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D defines health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 single items are combined to obtain a single index score that is health utility index (HUI) score reflecting subject's preferences for different health states. The lowest possible score is -0.59 and the highest is 1.00, higher scores on the EQ-5D represent a better QoL.
Time frame: Baseline, Week 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012)
Population: Analysis population included participants who had at least one evaluable EuroQoL EQ-5D questionnaire and were also included in the ITT population. 'N' (number of participants analyzed) signifies participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 18 | 0.742 units on a scale | Standard Deviation 0.251 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 36 | 0.710 units on a scale | Standard Deviation 0.311 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 12 | 0.752 units on a scale | Standard Deviation 0.239 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 42 | 0.722 units on a scale | Standard Deviation 0.209 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 24 | 0.733 units on a scale | Standard Deviation 0.3 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 48 | 0.719 units on a scale | Standard Deviation 0.227 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 6 | 0.739 units on a scale | Standard Deviation 0.276 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 54 | 0.733 units on a scale | Standard Deviation 0.275 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 30 | 0.737 units on a scale | Standard Deviation 0.301 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 60 | 0.760 units on a scale | Standard Deviation 0.322 |
| Cetuximab Plus Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Baseline | 0.743 units on a scale | Standard Deviation 0.24 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 60 | 0.742 units on a scale | Standard Deviation 0.17 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Baseline | 0.749 units on a scale | Standard Deviation 0.235 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 6 | 0.769 units on a scale | Standard Deviation 0.254 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 12 | 0.775 units on a scale | Standard Deviation 0.246 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 18 | 0.755 units on a scale | Standard Deviation 0.235 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 24 | 0.761 units on a scale | Standard Deviation 0.265 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 30 | 0.790 units on a scale | Standard Deviation 0.23 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 36 | 0.711 units on a scale | Standard Deviation 0.309 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 42 | 0.689 units on a scale | Standard Deviation 0.307 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 48 | 0.770 units on a scale | Standard Deviation 0.216 |
| Capecitabine Plus Cisplatin | Quality of Life (QoL) Assessed by EuroQol 5Dimensions (EQ-5D) Questionnaire | Week 54 | 0.730 units on a scale | Standard Deviation 0.191 |
Secondary
Safety - Number of Participants With Adverse Events (AEs)
An Adverse Event (AE) is defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to Baseline during a clinical study with an investigational medicinal product (IMP), regardless of causal relationship and even if no IMP has been administered.
Time frame: Time from first dose up to Day 30 after last dose of study treatment, reported between day of first participant randomized, that is, 30 Jun 2008 until cut-off date (31 Mar 2012)
Population: The safety population included all participants who received at least one dose of any trial treatment that is, cetuximab, cisplatin, or capecitabine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab Plus Capecitabine Plus Cisplatin | Safety - Number of Participants With Adverse Events (AEs) | 446 participants |
| Capecitabine Plus Cisplatin | Safety - Number of Participants With Adverse Events (AEs) | 432 participants |