Gastric Cancer
Conditions
Brief summary
This 2 arm study will compare the efficacy and safety of bevacizumab in combination with capecitabine and cisplatin versus placebo in combination with capecitabine and cisplatin in participants who have not received prior chemotherapy for advanced or metastatic gastric cancer. Participants will be randomized to one of two treatment groups Bevacizumab + Capecitabine/Cisplatin (experimental arm) or Placebo + Capecitabine/Cisplatin (control arm).
Interventions
DRUGBevacizumab
7.5 mg/kg IV infusion on Day 1 of every 3-week cycle
DRUGPlacebo
Placebo matched to bevacizumab on Day 1 of every 3-week cycle
DRUGCapecitabine
1000 mg/m\^2 orally twice daily on Days 1-14 of every 3-week cycle
DRUGCisplatin
80 mg/m\^2 IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed adenocarcinoma of the stomach or gastro-oesophageal junction with inoperable, locally advanced or metastatic disease, not amenable to curative therapy * Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2 * Measurable disease or non-measurable but evaluable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST)
Exclusion criteria
* Previous chemotherapy for locally advanced or metastatic gastric cancer * Previous platinum or anti-angiogenic therapy * Radiotherapy within 28 days of randomization * Evidence of Central Nervous System (CNS) metastasis at baseline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Event (Death) | From randomization until death (up to 34 months) | Percentage of participants who died due to any cause was reported. As planned, ad hoc analysis was done for overall survival up to clinical cut-off date of 12 January 2012 (34 months), subsequent to the protocol-defined clinical cut-off date of 13 May 2011 (26 months). Overall survival was defined as the time between randomization and the date of death due to any cause. |
| Overall Survival | From randomization until death (up to 34 months) | Overall survival was defined as the time between randomization and the date of death due to any cause. Overall survival was estimated using Kaplan Meier method. Reported data included censored observations. Participants for whom no death was captured on the clinical database were censored at the most recent date they were known to be alive. As planned, ad hoc analysis was done for overall survival up to clinical clinical cut-off date of 12 January 2012 (34 months), subsequent to the protocol-defined clinical cut-off date of 13 May 2011 (26 months). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With PFS Events (Disease Progression/Death) During First-line Therapy | From randomization until disease progression or death (up to 26 months) | Progression of disease was defined as at least 20% increase in the sum of longest diameters of target lesions compared to the smallest sum of longest diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. PFS during first-line therapy was defined as the time between randomization and the date of first documented disease progression or death, whichever occurred first and only if it occurred no later than 28 days after last confirmed intake of any study medication and before the start of non-study antineoplastic treatment, according to RECIST. |
| PFS During First-line Therapy | From randomization until disease progression or death (up to 26 months) | PFS during first-line therapy was defined as time between randomization and date of first documented disease progression or death, whichever occurred first and only if it occurred no later than 28 days after last intake of any study medication and only if it occurred before start of non-study antineoplastic treatment, according to RECIST. Progression of disease was defined as at least 20% increase in sum of longest diameters of target lesions compared to smallest sum of longest diameters on-study & absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. PFS was estimated using Kaplan Meier method. Reported data included censored observations. Participants who neither progressed nor died in this interval, or who were lost to follow-up were censored at date of last tumor assessment/last follow-up within this time window. Participants for whom no post-baseline tumor assessments were available were censored at day of randomization. |
| Percentage of Participants With Disease Progression | From randomization until disease progression or death (up to 26 months) | Progression of disease was defined as at least 20% increase in the sum of longest diameters of target lesions compared to the smallest sum of longest diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. |
| Time to Progression | From randomization until disease progression or death (up to 26 months) | Time to progression was defined as the time between randomization and the first occurrence of disease progression. Progression of disease was defined as at least 20% increase in the sum of longest diameters of target lesions compared to the smallest sum of longest diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Time to progression was estimated using Kaplan Meier method. Reported data included censored observations. Participants who had not progressed at the time of study completion (including participants who had died before disease progression) or who were lost to follow-up were censored at the date of the last tumor assessment or last follow-up for progression of disease. Participants for whom no post-baseline tumor assessments were available were censored at day of randomization. |
| Percentage of Participants With Progression-Free Survival (PFS) Events (Disease Progression/Death) | From randomization until disease progression or death (up to 26 months) | Progression of disease was defined as at least 20 percent (%) increase in the sum of longest diameters of target lesions compared to the smallest sum of longest diameters on-study and absolute increase of at least 5 millimeters (mm), progression of existing non-target lesions, or presence of new lesions. PFS was defined as the time between randomization and the date of first documented disease progression or death, whichever occurred first, according to Response Evaluation Criteria In Solid Tumors (RECIST). |
| Duration of Response During First-Line Therapy | From randomization until disease progression or death (up to 26 months) | Duration of response during first-line therapy was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death (whichever occurs first) during first-line therapy. CR: disappearance of all target and non-TLs and normalization of tumor markers. Pathological lymph nodes must have short axis measures \<10 mm. PR: at least a 30 % decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of longest diameters. Duration of response was estimated using Kaplan Meier method. Reported data included censored observations. Participants who did not progress or die after they had had a confirmed response were censored at the date of their last tumor measurement or last follow-up for progression of disease during first line therapy. |
| Percentage of Participants With Disease Control During First-Line Therapy | From randomization until disease progression or death (up to 26 months) | Disease control was defined as stable disease(SD) for 6 weeks or longer, CR plus PR as assessed by RECIST criteria for participants with measurable disease.CR:disappearance of all TLs & normalization of tumor markers. Pathological lymph nodes must have short axis measures\<10 mm. PR:at least 30% decrease in sum of measures(longest diameter for tumor lesions and short axis measure for nodes)of TLs, taking as reference baseline sum of longest diameters.SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression taking as reference smallest sum of longest diameters on study. For participants without measurable disease, clinical benefit rate was defined as no clinical disease progression for \>/=6 weeks. Disease progression was defined as at least 20% increase in sum of diameters of TLs compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. |
| Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | From Cycle 1 until disease progression (up to 26 months) | EORTC QLQ-C30 included global health status (GHS)/quality of life (QOL), functional scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used a 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores were averaged and transformed to 0-100 scale; a higher score for Global Qol/functional scales=better level of QoL/functioning, or a higher score for symptom scale=greater degree of symptoms. |
| Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | From Cycle 1 until disease progression (up to 26 months) | The EORTC QLQ-STO22 is a gastric cancer quality of life questionnaire. There are 22 questions which comprise 5 scales (dysphagia, pain, reflux symptom, dietary restrictions, and anxiety) and 4 single items (dry mouth, hair loss, taste, body image). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms. |
| Percentage of Participants With Best Overall Response as Assessed by RECIST During First-Line Therapy | From randomization until disease progression or death (up to 26 months) | Best overall response during first-line therapy was defined as the occurrence of either a confirmed complete (CR) or a partial response (PR), as assessed by the RECIST criteria. CR: disappearance of all target and non-target lesions (TLs) and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (\<) 10 mm. PR: at least a 30 % decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of longest diameters. |
| Progression-Free Survival (PFS) | From randomization until disease progression or death (up to 26 months) | PFS was defined as the time between randomization and the date of first documented disease progression or death, whichever occurred first, according to RECIST. Progression of disease was defined as at least 20% increase in the sum of longest diameters of target lesions compared to the smallest sum of longest diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. PFS was estimated using Kaplan Meier method. Reported data included censored observations. Participants who had neither progressed nor died at the time of study completion or who were lost to follow-up were censored at the date of the last tumor assessment or last follow-up for progression of disease. Participants for whom no post-baseline tumor assessments were available were censored at day of randomization. |
Countries
China
Participant flow
Pre-assignment details
Study reported data up to clinical cut-off date 13 May 2011, as approximately half of the participants withdrew the study at clinical cut-off date. Ad hoc analysis was done for overall survival, with clinical cut-off date of 12 January 2012, subsequent to clinical cut-off date of 13 May 2011.
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab, Capecitabine and Cisplatin Participants received bevacizumab 7.5 mg/kg IV infusion on Day 1 of every 3-week cycle in combination with capecitabine 1000 mg/m\^2 orally twice daily (total daily dose 2000 mg/m\^2) on Days 1-14 of every 3-week cycle and cisplatin 80 mg/m\^2 IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles; until disease progression or unmanageable toxicity. | 100 |
| Placebo, Capecitabine and Cisplatin Participants received placebo matched to bevacizumab on Day 1 of every 3-week cycle in combination with capecitabine 1000 mg/m\^2 orally twice daily (total daily dose 2000 mg/m\^2) on Days 1-14 of every 3-week cycle and cisplatin 80 mg/m\^2 IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles; until disease progression or unmanageable toxicity. | 102 |
| Total | 202 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative/Other than specified | 5 | 4 |
| Overall Study | Adverse Event | 14 | 17 |
| Overall Study | Death | 2 | 3 |
| Overall Study | Failure to return | 11 | 11 |
| Overall Study | Insufficient therapeutic response | 53 | 55 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Randomized but not treated | 0 | 1 |
| Overall Study | Refused treatment/Did not cooperate | 12 | 10 |
Baseline characteristics
| Characteristic | Bevacizumab, Capecitabine and Cisplatin | Placebo, Capecitabine and Cisplatin | Total |
|---|---|---|---|
| Age, Continuous | 54.2 years STANDARD_DEVIATION 11.66 | 55.5 years STANDARD_DEVIATION 12.14 | 54.9 years STANDARD_DEVIATION 11.89 |
| Gender Female | 32 Participants | 28 Participants | 60 Participants |
| Gender Male | 68 Participants | 74 Participants | 142 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 94 / 100 | 95 / 101 |
| serious Total, serious adverse events | 19 / 100 | 21 / 101 |
Outcome results
Primary
Overall Survival
Overall survival was defined as the time between randomization and the date of death due to any cause. Overall survival was estimated using Kaplan Meier method. Reported data included censored observations. Participants for whom no death was captured on the clinical database were censored at the most recent date they were known to be alive. As planned, ad hoc analysis was done for overall survival up to clinical clinical cut-off date of 12 January 2012 (34 months), subsequent to the protocol-defined clinical cut-off date of 13 May 2011 (26 months).
Time frame: From randomization until death (up to 34 months)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab, Capecitabine and Cisplatin | Overall Survival | 10.5 months |
| Placebo, Capecitabine and Cisplatin | Overall Survival | 11.4 months |
p-value: 0.863695% CI: [0.75, 1.41]Log Rank
Primary
Percentage of Participants With Event (Death)
Percentage of participants who died due to any cause was reported. As planned, ad hoc analysis was done for overall survival up to clinical cut-off date of 12 January 2012 (34 months), subsequent to the protocol-defined clinical cut-off date of 13 May 2011 (26 months). Overall survival was defined as the time between randomization and the date of death due to any cause.
Time frame: From randomization until death (up to 34 months)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab, Capecitabine and Cisplatin | Percentage of Participants With Event (Death) | 77.0 percentage of participants |
| Placebo, Capecitabine and Cisplatin | Percentage of Participants With Event (Death) | 75.5 percentage of participants |
Secondary
Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time
The EORTC QLQ-STO22 is a gastric cancer quality of life questionnaire. There are 22 questions which comprise 5 scales (dysphagia, pain, reflux symptom, dietary restrictions, and anxiety) and 4 single items (dry mouth, hair loss, taste, body image). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms.
Time frame: From Cycle 1 until disease progression (up to 26 months)
Population: ITT population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Pain | -0.97 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Dry Mouth | -0.19 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Eating Restrictions | -0.30 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Taste | -0.44 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Reflux Symptoms | -0.27 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Body Image | 0.27 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Anxiety | -0.17 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Hair Loss | -0.35 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Dysphagia | -0.31 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Hair Loss | -0.61 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Dysphagia | -0.05 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Pain | -0.52 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Reflux Symptoms | -0.43 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Eating Restrictions | -0.36 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Anxiety | -0.73 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Dry Mouth | 0.68 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Taste | -0.66 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time | Body Image | 0.13 scores on scale |
Secondary
Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time
EORTC QLQ-C30 included global health status (GHS)/quality of life (QOL), functional scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used a 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores were averaged and transformed to 0-100 scale; a higher score for Global Qol/functional scales=better level of QoL/functioning, or a higher score for symptom scale=greater degree of symptoms.
Time frame: From Cycle 1 until disease progression (up to 26 months)
Population: ITT population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Cognitive Functioning | -0.51 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Pain | -0.55 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Physical Funtioning | -0.89 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Dyspnoea | -0.10 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Social Functioning | -0.27 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Insomnia | -0.57 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Emotional Functioning | -0.22 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Appetite Loss | -0.65 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Fatigue | -0.36 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Constipation | -0.14 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Role Functioning | -0.65 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Diarrhoea | -0.29 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Nausea and Vomiting | -0.82 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Financial Difficulties | 0.31 scores on scale |
| Bevacizumab, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | GHS/QOL | 1.24 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Financial Difficulties | 0.04 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | GHS/QOL | 0.73 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Physical Funtioning | -0.99 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Role Functioning | -0.37 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Emotional Functioning | 0.19 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Cognitive Functioning | -0.41 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Social Functioning | 0.08 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Fatigue | -0.27 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Nausea and Vomiting | -0.55 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Pain | -0.22 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Dyspnoea | -0.07 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Insomnia | 0.26 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Appetite Loss | -1.17 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Constipation | -0.02 scores on scale |
| Placebo, Capecitabine and Cisplatin | Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time | Diarrhoea | 0.00 scores on scale |
Secondary
Duration of Response During First-Line Therapy
Duration of response during first-line therapy was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death (whichever occurs first) during first-line therapy. CR: disappearance of all target and non-TLs and normalization of tumor markers. Pathological lymph nodes must have short axis measures \<10 mm. PR: at least a 30 % decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of longest diameters. Duration of response was estimated using Kaplan Meier method. Reported data included censored observations. Participants who did not progress or die after they had had a confirmed response were censored at the date of their last tumor measurement or last follow-up for progression of disease during first line therapy.
Time frame: From randomization until disease progression or death (up to 26 months)
Population: Measurable disease population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab, Capecitabine and Cisplatin | Duration of Response During First-Line Therapy | 7.2 months |
| Placebo, Capecitabine and Cisplatin | Duration of Response During First-Line Therapy | 5.8 months |
p-value: 0.046295% CI: [0.29, 1]Log Rank
Secondary
Percentage of Participants With Best Overall Response as Assessed by RECIST During First-Line Therapy
Best overall response during first-line therapy was defined as the occurrence of either a confirmed complete (CR) or a partial response (PR), as assessed by the RECIST criteria. CR: disappearance of all target and non-target lesions (TLs) and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (\<) 10 mm. PR: at least a 30 % decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of longest diameters.
Time frame: From randomization until disease progression or death (up to 26 months)
Population: Measurable disease population included all randomized participants who had measurable disease at baseline according to RECIST.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab, Capecitabine and Cisplatin | Percentage of Participants With Best Overall Response as Assessed by RECIST During First-Line Therapy | 40.7 percentage of participants |
| Placebo, Capecitabine and Cisplatin | Percentage of Participants With Best Overall Response as Assessed by RECIST During First-Line Therapy | 33.7 percentage of participants |
p-value: 0.34895% CI: [-8.3, 22.4]Chi-squared
Secondary
Percentage of Participants With Disease Control During First-Line Therapy
Disease control was defined as stable disease(SD) for 6 weeks or longer, CR plus PR as assessed by RECIST criteria for participants with measurable disease.CR:disappearance of all TLs & normalization of tumor markers. Pathological lymph nodes must have short axis measures\<10 mm. PR:at least 30% decrease in sum of measures(longest diameter for tumor lesions and short axis measure for nodes)of TLs, taking as reference baseline sum of longest diameters.SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression taking as reference smallest sum of longest diameters on study. For participants without measurable disease, clinical benefit rate was defined as no clinical disease progression for \>/=6 weeks. Disease progression was defined as at least 20% increase in sum of diameters of TLs compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
Time frame: From randomization until disease progression or death (up to 26 months)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab, Capecitabine and Cisplatin | Percentage of Participants With Disease Control During First-Line Therapy | 73.0 percentage of participants |
| Placebo, Capecitabine and Cisplatin | Percentage of Participants With Disease Control During First-Line Therapy | 72.5 percentage of participants |
p-value: 0.942695% CI: [-12.4, 13.3]Chi-squared
Secondary
Percentage of Participants With Disease Progression
Progression of disease was defined as at least 20% increase in the sum of longest diameters of target lesions compared to the smallest sum of longest diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
Time frame: From randomization until disease progression or death (up to 26 months)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab, Capecitabine and Cisplatin | Percentage of Participants With Disease Progression | 56.0 percentage of participants |
| Placebo, Capecitabine and Cisplatin | Percentage of Participants With Disease Progression | 53.9 percentage of participants |
Secondary
Percentage of Participants With PFS Events (Disease Progression/Death) During First-line Therapy
Progression of disease was defined as at least 20% increase in the sum of longest diameters of target lesions compared to the smallest sum of longest diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. PFS during first-line therapy was defined as the time between randomization and the date of first documented disease progression or death, whichever occurred first and only if it occurred no later than 28 days after last confirmed intake of any study medication and before the start of non-study antineoplastic treatment, according to RECIST.
Time frame: From randomization until disease progression or death (up to 26 months)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab, Capecitabine and Cisplatin | Percentage of Participants With PFS Events (Disease Progression/Death) During First-line Therapy | 51.0 percentage of participants |
| Placebo, Capecitabine and Cisplatin | Percentage of Participants With PFS Events (Disease Progression/Death) During First-line Therapy | 59.8 percentage of participants |
Secondary
Percentage of Participants With Progression-Free Survival (PFS) Events (Disease Progression/Death)
Progression of disease was defined as at least 20 percent (%) increase in the sum of longest diameters of target lesions compared to the smallest sum of longest diameters on-study and absolute increase of at least 5 millimeters (mm), progression of existing non-target lesions, or presence of new lesions. PFS was defined as the time between randomization and the date of first documented disease progression or death, whichever occurred first, according to Response Evaluation Criteria In Solid Tumors (RECIST).
Time frame: From randomization until disease progression or death (up to 26 months)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab, Capecitabine and Cisplatin | Percentage of Participants With Progression-Free Survival (PFS) Events (Disease Progression/Death) | 81.0 percentage of participants |
| Placebo, Capecitabine and Cisplatin | Percentage of Participants With Progression-Free Survival (PFS) Events (Disease Progression/Death) | 81.4 percentage of participants |
Secondary
PFS During First-line Therapy
PFS during first-line therapy was defined as time between randomization and date of first documented disease progression or death, whichever occurred first and only if it occurred no later than 28 days after last intake of any study medication and only if it occurred before start of non-study antineoplastic treatment, according to RECIST. Progression of disease was defined as at least 20% increase in sum of longest diameters of target lesions compared to smallest sum of longest diameters on-study & absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. PFS was estimated using Kaplan Meier method. Reported data included censored observations. Participants who neither progressed nor died in this interval, or who were lost to follow-up were censored at date of last tumor assessment/last follow-up within this time window. Participants for whom no post-baseline tumor assessments were available were censored at day of randomization.
Time frame: From randomization until disease progression or death (up to 26 months)
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab, Capecitabine and Cisplatin | PFS During First-line Therapy | 6.3 months |
| Placebo, Capecitabine and Cisplatin | PFS During First-line Therapy | 6.1 months |
p-value: 0.368595% CI: [0.58, 1.22]Log Rank
Secondary
Progression-Free Survival (PFS)
PFS was defined as the time between randomization and the date of first documented disease progression or death, whichever occurred first, according to RECIST. Progression of disease was defined as at least 20% increase in the sum of longest diameters of target lesions compared to the smallest sum of longest diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. PFS was estimated using Kaplan Meier method. Reported data included censored observations. Participants who had neither progressed nor died at the time of study completion or who were lost to follow-up were censored at the date of the last tumor assessment or last follow-up for progression of disease. Participants for whom no post-baseline tumor assessments were available were censored at day of randomization.
Time frame: From randomization until disease progression or death (up to 26 months)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab, Capecitabine and Cisplatin | Progression-Free Survival (PFS) | 6.3 months |
| Placebo, Capecitabine and Cisplatin | Progression-Free Survival (PFS) | 6.0 months |
p-value: 0.470995% CI: [0.66, 1.21]Log Rank
Secondary
Time to Progression
Time to progression was defined as the time between randomization and the first occurrence of disease progression. Progression of disease was defined as at least 20% increase in the sum of longest diameters of target lesions compared to the smallest sum of longest diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Time to progression was estimated using Kaplan Meier method. Reported data included censored observations. Participants who had not progressed at the time of study completion (including participants who had died before disease progression) or who were lost to follow-up were censored at the date of the last tumor assessment or last follow-up for progression of disease. Participants for whom no post-baseline tumor assessments were available were censored at day of randomization.
Time frame: From randomization until disease progression or death (up to 26 months)
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab, Capecitabine and Cisplatin | Time to Progression | 6.5 months |
| Placebo, Capecitabine and Cisplatin | Time to Progression | 7.0 months |
p-value: 0.858995% CI: [0.67, 1.41]Log Rank