Neoplasms
Conditions
Brief summary
This 2 arm study will assess the efficacy and safety of two systemic treatments including Avastin in patients with previously-untreated progressive locally advanced/metastatic well-differentiated digestive endocrine tumors. Patients with duodeno-pancreatic tumors (arm 1) will be treated with 5FU/streptozotocin iv (5FU 400mg/m2/d D1 to D5;streptozotocin 500mg/m2/d/iv D1 to D5;D1=D42) every 6 weeks, plus Avastin 7.5mg/kg iv every 3 weeks. Patients with gastrointestinal tract tumors (arm 2) will be treated with Xeloda 1000mg/m2 po bid D1 to D14 plus Avastin 7.5mg/kg iv D1=D21 every 3 weeks. The patients will be treated with chemotherapy for a minimum of 6 months, unless there is tumor progression and/or unacceptable toxicity. The anticipated time on study treatment is until disease progression or unacceptable toxicity, and the target sample size is \<100 individuals.
Interventions
DRUGbevacizumab [Avastin]
7.5mg/kg iv on day 1 every 3 weeks
DRUG5 FU
400mg/m2/day iv on days 1-5 every 6 weeks
DRUGStreptozotocin
500mg/m2/day iv on days 1-5 every 6 weeks
DRUGXeloda
1000mg/m2 po bid on days 1-14 every 3 weeks
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult patients, \>=18 years of age; * well-differentiated gastrointestinal tract endocrine tumors, or duodeno-pancreatic endocrine tumors; * no previous anti-cancer therapy, other than surgery; * progressive metastatic disease; * \>=1 measurable lesion.
Exclusion criteria
* abnormal cardiac function, with history of ischemic heart disease in past 6 months and/or abnormal 12 lead ECG; * patients with known bleeding disorders; * unstable systemic disease; * chronic daily treatment with high-dose aspirin, NSAIDs or corticosteroids; * previous history of malignancy (other than successfully treated basal and squamous cell cancer of the skin, and/or in situ cancer of the cervix).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) - Percentage of Participants With an Event | Screening, every 3 months during treatment, every 6 months during follow-up to 2 years | PFS is defined as the interval between the date of start of treatment and the date of evaluation by the investigator of progressive disease or death from any cause. The progression was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) using medical imaging during the treatment period and by the investigators (confirmed by medical imaging) during the follow-up period. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of disease progression or death were censored at the date of the last visit or follow-up without progression. |
| PFS - Time to Event | Screening, every 3 months during treatment, every 6 months during follow-up to 2 years | PFS is defined as the interval between the date of start of treatment and the date of evaluation by the investigator of progressive disease or death from any cause. The progression was assessed according to RECIST using medical imaging during the treatment period and by the investigators (confirmed by medical imaging) during the follow-up period. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of disease progression or death were censored at the date of the last visit or follow-up without progression. Median PFS was estimated using the Kaplan-Meier method. |
| PFS - Percentage of Participants Estimated to be Progression Free at 12 and 24 Months | Screening, every 3 months during treatment, every 6 months during follow-up to 2 years | PFS is defined as the interval between the date of start of treatment and the date of evaluation by the investigator of progressive disease or death from any cause. The progression was assessed according to RECIST using medical imaging during the treatment period and by the investigators (confirmed by medical imaging) during the follow-up period. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of disease progression or death were censored at the date of the last visit or follow-up without progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of OR - Percentage of Participants With Sustained Response at 12 and 24 Months | Screening, every 3 months during treatment, every 6 months during follow-up to 2 years | Duration of OR was determined only for those participants with an overall response of CR or PR and was defined as the time interval between the response (CR or PR) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression. |
| Duration of Overall Disease Control (ODC) - Percentage of Participants With an Event | Screening, every 3 months during treatment, every 6 months during follow-up to 2 years | Determined only for those participants with overall disease control (CR, PR or SD per RECIST) and was defined as the time interval between the first occurrence of disease control (CR, PR or SD) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression. |
| Duration of ODC - Time to Event | Screening, every 3 months during treatment, every 6 months during follow-up to 2 years | Determined only for those participants with overall control disease (CR, PR, or SD per RECIST) and was defined as the time interval between the first occurrence of disease control (CR, PR or SD) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression. Median time to event was estimated using the Kaplan-Meier method. |
| Duration of ODC - Percentage of Participants Maintaining Disease Control at 12 and 24 Months | Screening, every 3 months during treatment, every 6 months during follow-up to 2 years | Duration of ODC was determined only for those participants with overall control disease (CR, PR, or SD per RECIST) and was defined as the time interval between the first occurrence of disease control (CR, PR, or SD) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression. |
| Overall Survival (OS) - Percentage of Participants With an Event | Screening, Day 1 of every cycle during treatment, every 6 months during follow-up to 2 years | OS was defined as the time from the first treatment administration to death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation. Data for participants who were alive at the end of the study were censored at the date of last visit. |
| Percentage of Participants With a Response by Best Overall Response | Screening, every 3 months during treatment, every 6 months during follow-up to 2 years | Best overall response defined as best response recorded during the study as defined according to RECIST; performed by the investigator and by centralized review. Complete response (CR): complete disappearance of all target lesions and non-target disease. All lesions, both target and non-target, must have decreased to normal (short axis, less than \[\<\]10 millimeters \[mm\]). No new lesions. Partial response (PR): greater than or equal to (≥)30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter (LD) was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease (SD): not qualifying for CR, PR, or Progressive Disease (PD). PD: at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. |
| OS - Percentage of Participants Surviving at 12 and 24 Months | Screening, Day 1 of every cycle during treatment, every 6 months during follow-up to 2 years | OS was defined as the time from the first treatment administration to death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation. Data for participants who were alive at the end of the study were censored at the date of last visit. |
| Global Health Status as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) | Screening, every 3 months during treatment | EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale \[1 'very poor' to 7 'Excellent'\]). Scores were averaged and transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms. |
| Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | Screening, every 3 months during treatment | EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale \[1 'very poor' to 7 'Excellent'\]). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms. Changes from baseline were categorized as follows: Very much worsening (less than \[\<\]-20); Moderate worsening (greater than or equal to \[≥\]-20 to \<-10); Little worsening (≥-10 to \<-5); No change (≥-5 to less than or equal to \[≤\]5); Little improvement (\>5 to ≤10); Moderate improvement (\>10 to ≤20); and Very much improved (\>20). |
| EORTC QLQ-C30 Functional and Symptom Scale Scores | Screening, every 3 months during treatment | EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale \[1 'very poor' to 7 'Excellent'\]). Scores averaged, transformed to 0-100 scale; for functional scores, a higher score represents a better level of functioning. For symptom scale scores a higher level represents a more severe level of symptoms. |
| OS - Time to Event | Screening, Day 1 of every cycle during treatment, every 6 months during follow-up to 2 years | OS was defined as the time from the first treatment administration to death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation. Data for participants who were alive at the end of the study were censored at the date of last visit. Median OS was estimated using the Kaplan-Meier method. |
| Duration of Overall Response (OR) - Percentage of Participants With an Event | Screening, every 3 months during treatment, every 6 months during follow-up to 2 years | Determined only for those participants with an overall response (CR or PR) and was defined as the time interval between the response (CR or PR) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression. |
| Duration of OR - Time to Event | Screening, every 3 months during treatment, every 6 months during follow-up to 2 years | Determined only for those participants with an overall response (CR or PR) and was defined as the time interval between the response (CR or PR) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression. Median duration of OR was estimated using the Kaplan-Meier method. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab + 5-FU + Streptozocin Cycles 1-5 (42-day cycles): Participants received bevacizumab 7.5 mg/kg IV on Days 1 and 22; 5-FU 400 mg/m\^2/day IV on Days 1 through 5; and streptozocin 500 mg/m\^2/day IV on Days 1 through 5. Days 5-21 and 23-42 were rest periods. This 42-day cycle was repeated at least 4 times. | 34 |
| Bevacizumab + Capecitabine Cycles 1-9 (21-day cycles): Participants received bevacizumab 7.5 mg/kg IV on Day 1; capecitabine 1000 mg/m\^2, tablets, PO, BID on Days 1 through 14. Days 15-21 were a rest period. This 21-day cycle was repeated at least 8 times. | 49 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 8 |
| Overall Study | Investigator's decision (progression) | 1 | 0 |
Baseline characteristics
| Characteristic | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine | Total |
|---|---|---|---|
| Age, Continuous | 55.93 years STANDARD_DEVIATION 10.63 | 61.64 years STANDARD_DEVIATION 9.2 | 59.29 years STANDARD_DEVIATION 10.15 |
| Sex: Female, Male Female | 12 Participants | 23 Participants | 35 Participants |
| Sex: Female, Male Male | 22 Participants | 26 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 34 / 34 | 49 / 49 |
| serious Total, serious adverse events | 11 / 34 | 13 / 49 |
Outcome results
Primary
PFS - Percentage of Participants Estimated to be Progression Free at 12 and 24 Months
PFS is defined as the interval between the date of start of treatment and the date of evaluation by the investigator of progressive disease or death from any cause. The progression was assessed according to RECIST using medical imaging during the treatment period and by the investigators (confirmed by medical imaging) during the follow-up period. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of disease progression or death were censored at the date of the last visit or follow-up without progression.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + 5-FU + Streptozocin | PFS - Percentage of Participants Estimated to be Progression Free at 12 and 24 Months | 12 months | 76 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | PFS - Percentage of Participants Estimated to be Progression Free at 12 and 24 Months | 24 months | 50 percentage of participants |
| Bevacizumab + Capecitabine | PFS - Percentage of Participants Estimated to be Progression Free at 12 and 24 Months | 12 months | 65 percentage of participants |
| Bevacizumab + Capecitabine | PFS - Percentage of Participants Estimated to be Progression Free at 12 and 24 Months | 24 months | 48 percentage of participants |
Primary
PFS - Time to Event
PFS is defined as the interval between the date of start of treatment and the date of evaluation by the investigator of progressive disease or death from any cause. The progression was assessed according to RECIST using medical imaging during the treatment period and by the investigators (confirmed by medical imaging) during the follow-up period. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of disease progression or death were censored at the date of the last visit or follow-up without progression. Median PFS was estimated using the Kaplan-Meier method.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + 5-FU + Streptozocin | PFS - Time to Event | 23.7 months |
| Bevacizumab + Capecitabine | PFS - Time to Event | 23.4 months |
Primary
Progression-Free Survival (PFS) - Percentage of Participants With an Event
PFS is defined as the interval between the date of start of treatment and the date of evaluation by the investigator of progressive disease or death from any cause. The progression was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) using medical imaging during the treatment period and by the investigators (confirmed by medical imaging) during the follow-up period. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of disease progression or death were censored at the date of the last visit or follow-up without progression.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + 5-FU + Streptozocin | Progression-Free Survival (PFS) - Percentage of Participants With an Event | 52.9 percentage of participants |
| Bevacizumab + Capecitabine | Progression-Free Survival (PFS) - Percentage of Participants With an Event | 53.1 percentage of participants |
Secondary
Duration of ODC - Percentage of Participants Maintaining Disease Control at 12 and 24 Months
Duration of ODC was determined only for those participants with overall control disease (CR, PR, or SD per RECIST) and was defined as the time interval between the first occurrence of disease control (CR, PR, or SD) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Population: ITT population; only participants with a response (CR, PR, or SD) were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + 5-FU + Streptozocin | Duration of ODC - Percentage of Participants Maintaining Disease Control at 12 and 24 Months | 12 months | 68 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Duration of ODC - Percentage of Participants Maintaining Disease Control at 12 and 24 Months | 24 months | 42 percentage of participants |
| Bevacizumab + Capecitabine | Duration of ODC - Percentage of Participants Maintaining Disease Control at 12 and 24 Months | 12 months | 72 percentage of participants |
| Bevacizumab + Capecitabine | Duration of ODC - Percentage of Participants Maintaining Disease Control at 12 and 24 Months | 24 months | NA percentage of participants |
Secondary
Duration of ODC - Time to Event
Determined only for those participants with overall control disease (CR, PR, or SD per RECIST) and was defined as the time interval between the first occurrence of disease control (CR, PR or SD) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression. Median time to event was estimated using the Kaplan-Meier method.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Population: ITT population; only participants with a response (CR, PR, or SD) were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + 5-FU + Streptozocin | Duration of ODC - Time to Event | 22.3 months |
| Bevacizumab + Capecitabine | Duration of ODC - Time to Event | 23.4 months |
Secondary
Duration of OR - Percentage of Participants With Sustained Response at 12 and 24 Months
Duration of OR was determined only for those participants with an overall response of CR or PR and was defined as the time interval between the response (CR or PR) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + 5-FU + Streptozocin | Duration of OR - Percentage of Participants With Sustained Response at 12 and 24 Months | 12 months | 74 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Duration of OR - Percentage of Participants With Sustained Response at 12 and 24 Months | 24 months | 55 percentage of participants |
| Bevacizumab + Capecitabine | Duration of OR - Percentage of Participants With Sustained Response at 12 and 24 Months | 12 months | 70 percentage of participants |
| Bevacizumab + Capecitabine | Duration of OR - Percentage of Participants With Sustained Response at 12 and 24 Months | 24 months | NA percentage of participants |
Secondary
Duration of OR - Time to Event
Determined only for those participants with an overall response (CR or PR) and was defined as the time interval between the response (CR or PR) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression. Median duration of OR was estimated using the Kaplan-Meier method.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Population: ITT population; only participants with a response of CR or PR were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + 5-FU + Streptozocin | Duration of OR - Time to Event | NA months |
| Bevacizumab + Capecitabine | Duration of OR - Time to Event | NA months |
Secondary
Duration of Overall Disease Control (ODC) - Percentage of Participants With an Event
Determined only for those participants with overall disease control (CR, PR or SD per RECIST) and was defined as the time interval between the first occurrence of disease control (CR, PR or SD) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + 5-FU + Streptozocin | Duration of Overall Disease Control (ODC) - Percentage of Participants With an Event | 52.9 percentage of participants |
| Bevacizumab + Capecitabine | Duration of Overall Disease Control (ODC) - Percentage of Participants With an Event | 46.5 percentage of participants |
Secondary
Duration of Overall Response (OR) - Percentage of Participants With an Event
Determined only for those participants with an overall response (CR or PR) and was defined as the time interval between the response (CR or PR) and the date of progression or death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation without progression. Data for participants who completed the study without an event of progression or death were censored at the data of last visit or follow-up without progression.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Population: ITT population; only participants with a response of CR or PR were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + 5-FU + Streptozocin | Duration of Overall Response (OR) - Percentage of Participants With an Event | 42.1 percentage of participants |
| Bevacizumab + Capecitabine | Duration of Overall Response (OR) - Percentage of Participants With an Event | 22.2 percentage of participants |
Secondary
EORTC QLQ-C30 Functional and Symptom Scale Scores
EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale \[1 'very poor' to 7 'Excellent'\]). Scores averaged, transformed to 0-100 scale; for functional scores, a higher score represents a better level of functioning. For symptom scale scores a higher level represents a more severe level of symptoms.
Time frame: Screening, every 3 months during treatment
Population: ITT population; only participants who completed the questionnaire at baseline and who had at least 1 post-baseline assessment were included in the analysis. n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Physical functioning, Baseline (n=30,43) | 90.44 units on a scale | Standard Deviation 13.3 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Physical functioning, 3 months (n=22,33) | 89.32 units on a scale | Standard Deviation 12.77 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Physical functioning, 6 months (n=21,24) | 81.98 units on a scale | Standard Deviation 19.75 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Physical functioning, End of Treatment (n=13,24) | 82.82 units on a scale | Standard Deviation 20.21 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Role functioning, Baseline (n=30,43) | 82.22 units on a scale | Standard Deviation 27.31 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Role functioning, 3 months (n=22,33) | 85.61 units on a scale | Standard Deviation 21.39 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Role functioning, 6 months (n=21,24) | 75.40 units on a scale | Standard Deviation 29.16 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Role functioning, End of Treatment (n=13,24) | 78.21 units on a scale | Standard Deviation 32.9 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Emotional functioning, Baseline (n=30,42) | 71.94 units on a scale | Standard Deviation 28.32 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Emotional functioning, 3 months (n=21,33) | 81.48 units on a scale | Standard Deviation 20.53 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Emotional functioning, 6 months (n=21,24) | 72.62 units on a scale | Standard Deviation 28.28 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Emotional functioning, End of Treatment (n=13,24) | 77.56 units on a scale | Standard Deviation 23.17 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Cognitive functioning, Baseline (n=30,42) | 86.67 units on a scale | Standard Deviation 18.26 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Cognitive functioning, 3 months (n=22,33) | 89.39 units on a scale | Standard Deviation 15.04 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Cognitive functioning, 6 months (n=21,24) | 83.33 units on a scale | Standard Deviation 21.08 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Cognitive functioning, End of Treatment (n=13,24) | 83.33 units on a scale | Standard Deviation 22.57 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Social functioning, Baseline (n=30,41) | 86.11 units on a scale | Standard Deviation 21.48 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Social functioning, 3 months (n=22,33) | 89.39 units on a scale | Standard Deviation 17.48 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Social functioning, 6 months (n=21,24) | 81.75 units on a scale | Standard Deviation 26.3 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Social functioning, End of Treatment (n=13,24) | 84.62 units on a scale | Standard Deviation 24.96 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Fatigue, Baseline (n=30,42) | 26.30 units on a scale | Standard Deviation 23.61 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Fatigue, 3 months (n=21,33) | 27.78 units on a scale | Standard Deviation 23.7 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Fatigue, 6 months (n=20,24) | 36.67 units on a scale | Standard Deviation 29.09 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Fatigue, End of Treatment (n=13,24) | 34.19 units on a scale | Standard Deviation 28.85 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Nausea and vomiting, Baseline (n=30,42) | 6.67 units on a scale | Standard Deviation 14.91 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Nausea and vomiting, 3 months (n=22,33) | 10.61 units on a scale | Standard Deviation 14.13 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Nausea and vomiting, 6 months (n=21,24) | 8.73 units on a scale | Standard Deviation 17.97 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Nausea and vomiting, End of Treatment (n=13,24) | 10.26 units on a scale | Standard Deviation 19.88 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Pain, Baseline (n=30,43) | 14.44 units on a scale | Standard Deviation 19.44 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Pain, 3 months (n=22,33) | 12.88 units on a scale | Standard Deviation 18.5 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Pain, 6 months (n=21,24) | 23.02 units on a scale | Standard Deviation 31.83 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Pain, End of Treatment (n=13,24) | 20.51 units on a scale | Standard Deviation 28.18 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Dyspnea, Baseline (n=30,43) | 16.67 units on a scale | Standard Deviation 25.89 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Dyspnea, 3 months (n=21,33) | 12.70 units on a scale | Standard Deviation 19.65 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Dyspnea, 6 months (n=21,23) | 19.05 units on a scale | Standard Deviation 24.88 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Dyspnea, End of Treatment (n=13,24) | 20.51 units on a scale | Standard Deviation 28.99 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Insomnia, Baseline (n=30,43) | 24.44 units on a scale | Standard Deviation 27.59 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Insomnia, 3 months (n=21,33) | 20.63 units on a scale | Standard Deviation 22.3 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Insomnia, 6 months (n=21,24) | 33.33 units on a scale | Standard Deviation 34.96 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Insomnia, End of Treatment (n=13,24) | 23.08 units on a scale | Standard Deviation 25.04 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Appetite loss, Baseline (n=29,42) | 12.64 units on a scale | Standard Deviation 16.46 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Appetite loss, 3 months (n=22,33) | 7.58 units on a scale | Standard Deviation 14.3 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Appetite loss, 6 months (n=21,24) | 15.87 units on a scale | Standard Deviation 27.12 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Appetite loss, End of Treatment (n=13,24) | 12.82 units on a scale | Standard Deviation 28.99 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Constipation, Baseline (n=27,40) | 4.94 units on a scale | Standard Deviation 15.2 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Constipation, 3 months (n=21,33) | 15.87 units on a scale | Standard Deviation 27.12 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Constipation, 6 months (n=21,23) | 17.46 units on a scale | Standard Deviation 27.12 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Constipation, End of Treatment (n=13,24) | 12.82 units on a scale | Standard Deviation 21.68 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Diarrhea, Baseline (n=30,41) | 13.33 units on a scale | Standard Deviation 24.13 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Diarrhea, 3 months (n=22,32) | 9.09 units on a scale | Standard Deviation 21.04 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Diarrhea, 6 months (n=21,23) | 6.35 units on a scale | Standard Deviation 17.06 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Diarrhea, End of Treatment (n=12,22) | 2.78 units on a scale | Standard Deviation 9.62 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Financial difficulties, Baseline (n=30,413) | 14.44 units on a scale | Standard Deviation 25.8 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Financial difficulties, 3 months (n=22,33) | 9.09 units on a scale | Standard Deviation 15.19 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Financial difficulties, 6 months (n=21,23) | 15.87 units on a scale | Standard Deviation 24.99 |
| Bevacizumab + 5-FU + Streptozocin | EORTC QLQ-C30 Functional and Symptom Scale Scores | Financial difficulties, End of treatment (n=13,24) | 17.95 units on a scale | Standard Deviation 25.88 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Financial difficulties, Baseline (n=30,413) | 8.13 units on a scale | Standard Deviation 17.92 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Physical functioning, Baseline (n=30,43) | 87.71 units on a scale | Standard Deviation 14.88 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Pain, Baseline (n=30,43) | 21.71 units on a scale | Standard Deviation 27.83 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Physical functioning, 3 months (n=22,33) | 75.35 units on a scale | Standard Deviation 24.07 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Appetite loss, 6 months (n=21,24) | 25.00 units on a scale | Standard Deviation 26.47 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Physical functioning, 6 months (n=21,24) | 82.50 units on a scale | Standard Deviation 18.21 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Pain, 3 months (n=22,33) | 18.18 units on a scale | Standard Deviation 25.47 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Physical functioning, End of Treatment (n=13,24) | 79.44 units on a scale | Standard Deviation 19.85 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Diarrhea, 3 months (n=22,32) | 45.83 units on a scale | Standard Deviation 34.65 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Role functioning, Baseline (n=30,43) | 83.33 units on a scale | Standard Deviation 25.46 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Pain, 6 months (n=21,24) | 17.36 units on a scale | Standard Deviation 19.95 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Role functioning, 3 months (n=22,33) | 62.12 units on a scale | Standard Deviation 33.66 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Appetite loss, End of Treatment (n=13,24) | 25.00 units on a scale | Standard Deviation 32.97 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Role functioning, 6 months (n=21,24) | 70.83 units on a scale | Standard Deviation 28.34 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Pain, End of Treatment (n=13,24) | 26.39 units on a scale | Standard Deviation 32.94 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Role functioning, End of Treatment (n=13,24) | 72.92 units on a scale | Standard Deviation 29 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Financial difficulties, 6 months (n=21,23) | 2.90 units on a scale | Standard Deviation 9.6 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Emotional functioning, Baseline (n=30,42) | 71.89 units on a scale | Standard Deviation 20.5 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Dyspnea, Baseline (n=30,43) | 16.28 units on a scale | Standard Deviation 25.59 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Emotional functioning, 3 months (n=21,33) | 76.01 units on a scale | Standard Deviation 24.27 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Constipation, Baseline (n=27,40) | 10.00 units on a scale | Standard Deviation 21.62 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Emotional functioning, 6 months (n=21,24) | 76.04 units on a scale | Standard Deviation 26.27 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Dyspnea, 3 months (n=21,33) | 30.30 units on a scale | Standard Deviation 32.66 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Emotional functioning, End of Treatment (n=13,24) | 73.61 units on a scale | Standard Deviation 24.04 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Diarrhea, 6 months (n=21,23) | 43.48 units on a scale | Standard Deviation 30.87 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Cognitive functioning, Baseline (n=30,42) | 87.30 units on a scale | Standard Deviation 16.38 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Dyspnea, 6 months (n=21,23) | 23.19 units on a scale | Standard Deviation 29.19 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Social functioning, Baseline (n=30,41) | 87.40 units on a scale | Standard Deviation 20.34 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Cognitive functioning, 3 months (n=22,33) | 83.84 units on a scale | Standard Deviation 21.03 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Constipation, 3 months (n=21,33) | 7.07 units on a scale | Standard Deviation 18.18 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Cognitive functioning, 6 months (n=21,24) | 82.64 units on a scale | Standard Deviation 18.04 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Dyspnea, End of Treatment (n=13,24) | 23.61 units on a scale | Standard Deviation 30.26 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Cognitive functioning, End of Treatment (n=13,24) | 81.94 units on a scale | Standard Deviation 25.97 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Financial difficulties, 3 months (n=22,33) | 6.06 units on a scale | Standard Deviation 15.49 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Insomnia, Baseline (n=30,43) | 24.03 units on a scale | Standard Deviation 24.48 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Social functioning, 3 months (n=22,33) | 75.76 units on a scale | Standard Deviation 27.35 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Constipation, 6 months (n=21,23) | 11.59 units on a scale | Standard Deviation 21.58 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Social functioning, 6 months (n=21,24) | 83.33 units on a scale | Standard Deviation 21.42 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Insomnia, 3 months (n=21,33) | 27.27 units on a scale | Standard Deviation 30.57 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Social functioning, End of Treatment (n=13,24) | 81.94 units on a scale | Standard Deviation 21.93 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Diarrhea, End of Treatment (n=12,22) | 28.79 units on a scale | Standard Deviation 31.36 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Fatigue, Baseline (n=30,42) | 27.25 units on a scale | Standard Deviation 21.7 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Insomnia, 6 months (n=21,24) | 29.17 units on a scale | Standard Deviation 30 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Fatigue, 3 months (n=21,33) | 43.10 units on a scale | Standard Deviation 31.76 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Constipation, End of Treatment (n=13,24) | 13.89 units on a scale | Standard Deviation 25.85 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Fatigue, 6 months (n=20,24) | 37.96 units on a scale | Standard Deviation 23.61 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Insomnia, End of Treatment (n=13,24) | 30.56 units on a scale | Standard Deviation 33.93 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Fatigue, End of Treatment (n=13,24) | 34.49 units on a scale | Standard Deviation 32.93 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Financial difficulties, End of treatment (n=13,24) | 4.17 units on a scale | Standard Deviation 14.95 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Nausea and vomiting, Baseline (n=30,42) | 2.78 units on a scale | Standard Deviation 7.29 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Appetite loss, Baseline (n=29,42) | 8.73 units on a scale | Standard Deviation 20.9 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Nausea and vomiting, 3 months (n=22,33) | 9.60 units on a scale | Standard Deviation 16.15 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Diarrhea, Baseline (n=30,41) | 37.40 units on a scale | Standard Deviation 31.79 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Nausea and vomiting, 6 months (n=21,24) | 7.64 units on a scale | Standard Deviation 12.98 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Appetite loss, 3 months (n=22,33) | 20.20 units on a scale | Standard Deviation 24.92 |
| Bevacizumab + Capecitabine | EORTC QLQ-C30 Functional and Symptom Scale Scores | Nausea and vomiting, End of Treatment (n=13,24) | 6.25 units on a scale | Standard Deviation 14.59 |
Secondary
Global Health Status as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30)
EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale \[1 'very poor' to 7 'Excellent'\]). Scores were averaged and transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.
Time frame: Screening, every 3 months during treatment
Population: ITT population; only participants who completed the questionnaire at baseline and who had at least 1 post-baseline assessment were included in the analysis. Number (n) equals (=) the number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bevacizumab + 5-FU + Streptozocin | Global Health Status as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) | 3 months (n=20,32) | 65.83 units on a scale | Standard Deviation 19.48 |
| Bevacizumab + 5-FU + Streptozocin | Global Health Status as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) | 12 months (n=13,14) | 66.03 units on a scale | Standard Deviation 17.83 |
| Bevacizumab + 5-FU + Streptozocin | Global Health Status as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) | 6 months (n=20,24) | 60.00 units on a scale | Standard Deviation 21.9 |
| Bevacizumab + 5-FU + Streptozocin | Global Health Status as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) | End of treatment (n=13,23) | 64.74 units on a scale | Standard Deviation 23.36 |
| Bevacizumab + 5-FU + Streptozocin | Global Health Status as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) | Baseline (n=29,40) | 65.23 units on a scale | Standard Deviation 23.89 |
| Bevacizumab + Capecitabine | Global Health Status as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) | End of treatment (n=13,23) | 57.97 units on a scale | Standard Deviation 28.48 |
| Bevacizumab + Capecitabine | Global Health Status as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) | Baseline (n=29,40) | 65.42 units on a scale | Standard Deviation 20.02 |
| Bevacizumab + Capecitabine | Global Health Status as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) | 3 months (n=20,32) | 57.03 units on a scale | Standard Deviation 22.41 |
| Bevacizumab + Capecitabine | Global Health Status as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) | 6 months (n=20,24) | 66.32 units on a scale | Standard Deviation 21.35 |
| Bevacizumab + Capecitabine | Global Health Status as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) | 12 months (n=13,14) | 72.62 units on a scale | Standard Deviation 19.46 |
Secondary
OS - Percentage of Participants Surviving at 12 and 24 Months
OS was defined as the time from the first treatment administration to death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation. Data for participants who were alive at the end of the study were censored at the date of last visit.
Time frame: Screening, Day 1 of every cycle during treatment, every 6 months during follow-up to 2 years
Population: ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + 5-FU + Streptozocin | OS - Percentage of Participants Surviving at 12 and 24 Months | 12 months | 94 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | OS - Percentage of Participants Surviving at 12 and 24 Months | 24 months | 88 percentage of participants |
| Bevacizumab + Capecitabine | OS - Percentage of Participants Surviving at 12 and 24 Months | 12 months | 88 percentage of participants |
| Bevacizumab + Capecitabine | OS - Percentage of Participants Surviving at 12 and 24 Months | 24 months | 85 percentage of participants |
Secondary
OS - Time to Event
OS was defined as the time from the first treatment administration to death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation. Data for participants who were alive at the end of the study were censored at the date of last visit. Median OS was estimated using the Kaplan-Meier method.
Time frame: Screening, Day 1 of every cycle during treatment, every 6 months during follow-up to 2 years
Population: ITT population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab + 5-FU + Streptozocin | OS - Time to Event | NA months |
| Bevacizumab + Capecitabine | OS - Time to Event | NA months |
Secondary
Overall Survival (OS) - Percentage of Participants With an Event
OS was defined as the time from the first treatment administration to death from any cause. Data for participants who were lost to follow-up were censored at the date of last evaluation. Data for participants who were alive at the end of the study were censored at the date of last visit.
Time frame: Screening, Day 1 of every cycle during treatment, every 6 months during follow-up to 2 years
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bevacizumab + 5-FU + Streptozocin | Overall Survival (OS) - Percentage of Participants With an Event | 14.7 percentage of participants |
| Bevacizumab + Capecitabine | Overall Survival (OS) - Percentage of Participants With an Event | 16.3 percentage of participants |
Secondary
Percentage of Participants With a Response by Best Overall Response
Best overall response defined as best response recorded during the study as defined according to RECIST; performed by the investigator and by centralized review. Complete response (CR): complete disappearance of all target lesions and non-target disease. All lesions, both target and non-target, must have decreased to normal (short axis, less than \[\<\]10 millimeters \[mm\]). No new lesions. Partial response (PR): greater than or equal to (≥)30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter (LD) was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. Stable disease (SD): not qualifying for CR, PR, or Progressive Disease (PD). PD: at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.
Time frame: Screening, every 3 months during treatment, every 6 months during follow-up to 2 years
Population: ITT population. Data were missing from centralized review for 1 participant.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With a Response by Best Overall Response | PR (Investigator) | 55.9 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With a Response by Best Overall Response | PR (Centralized review) | 51.5 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With a Response by Best Overall Response | SD (Investigator) | 44.1 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With a Response by Best Overall Response | SD (Centralized review) | 48.5 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With a Response by Best Overall Response | PD (Investigator) | 0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With a Response by Best Overall Response | PD (Centralized review) | 0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With a Response by Best Overall Response | Not evaluable (Investigator) | 0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With a Response by Best Overall Response | Not evaluable (Centralized review) | 0 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With a Response by Best Overall Response | Not evaluable (Centralized review) | 6.3 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With a Response by Best Overall Response | PR (Investigator) | 18.4 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With a Response by Best Overall Response | PD (Investigator) | 8.2 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With a Response by Best Overall Response | PR (Centralized review) | 12.5 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With a Response by Best Overall Response | Not evaluable (Investigator) | 4.1 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With a Response by Best Overall Response | SD (Investigator) | 69.4 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With a Response by Best Overall Response | PD (Centralized review) | 0 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With a Response by Best Overall Response | SD (Centralized review) | 81.3 percentage of participants |
Secondary
Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category
EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale \[1 'very poor' to 7 'Excellent'\]). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms. Changes from baseline were categorized as follows: Very much worsening (less than \[\<\]-20); Moderate worsening (greater than or equal to \[≥\]-20 to \<-10); Little worsening (≥-10 to \<-5); No change (≥-5 to less than or equal to \[≤\]5); Little improvement (\>5 to ≤10); Moderate improvement (\>10 to ≤20); and Very much improved (\>20).
Time frame: Screening, every 3 months during treatment
Population: ITT population; only participants who completed the questionnaire at baseline and who had at least 1 post-baseline assessment were included in the analysis. n=number of participants assessed for the specified parameter at a given visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 12 months, Very much worsening (n=12,13) | 8.3 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 3 months, Little improving (n=20,29) | 5.0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 12 months, Moderate worsening (n=12,13) | 8.3 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 6 months, Moderate worsening (n=20,22) | 10.0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 12 months - Little worsening (n=12,13) | 33.3 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 3 months, Moderate worsening (n=20,29) | 10.0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 12 months, No change (n=12,13) | 25.0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 6 months, Little worsening (n=20,22) | 5.0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 12 months, Little improving (n=12,13) | 8.3 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 3 months, Moderate Improving (n=20,29) | 15.0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 12 months, Moderate Improving (n=12,13) | 16.7 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 6 months, No change (n=20,22) | 35.0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 12 months, Very much improving (n=12,13) | 0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 3 months, No change (n=20,29) | 40.0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | End of treatment, Very much worsening (n=13,20) | 15.4 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 6 months, Little improving (n=20,22) | 10.0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | End of treatment, Moderate worsening (n=13,20) | 30.8 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 3 months, Very much improving (n=20,29) | 10.0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | End of treatment, Little worsening (n=13,20) | 0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 6 months, Moderate Improving (n=20,22) | 15.0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | End of treatment, No change (n=13,20) | 15.4 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 3 months, Little worsening (n=20,29) | 10.0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | End of treatment, Little improving (n=13,20) | 15.4 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 6 months, Very much improving (n=20,22) | 10.0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | End of treatment, Moderate Improving (n=13,20) | 15.4 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 6 months, Very much worsening (n=20,22) | 15.0 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | End of treatment, Very much improving (n=13,20) | 7.7 percentage of participants |
| Bevacizumab + 5-FU + Streptozocin | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 3 months, Very much worsening (n=20,29) | 10.0 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | End of treatment, Very much improving (n=13,20) | 10.0 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 3 months, Very much worsening (n=20,29) | 17.2 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 3 months, Moderate worsening (n=20,29) | 24.1 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 3 months, Little worsening (n=20,29) | 17.2 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 3 months, No change (n=20,29) | 24.1 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 3 months, Little improving (n=20,29) | 3.4 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 3 months, Moderate Improving (n=20,29) | 3.4 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 3 months, Very much improving (n=20,29) | 10.3 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 6 months, Very much worsening (n=20,22) | 22.7 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 6 months, Moderate worsening (n=20,22) | 18.2 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 6 months, Little worsening (n=20,22) | 0 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 6 months, No change (n=20,22) | 31.8 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 6 months, Little improving (n=20,22) | 13.6 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 6 months, Moderate Improving (n=20,22) | 0 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 6 months, Very much improving (n=20,22) | 13.6 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 12 months, Very much worsening (n=12,13) | 0 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 12 months, Moderate worsening (n=12,13) | 15.4 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 12 months - Little worsening (n=12,13) | 15.4 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 12 months, No change (n=12,13) | 38.5 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 12 months, Little improving (n=12,13) | 7.7 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 12 months, Moderate Improving (n=12,13) | 15.4 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | 12 months, Very much improving (n=12,13) | 7.7 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | End of treatment, Very much worsening (n=13,20) | 15.0 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | End of treatment, Moderate worsening (n=13,20) | 5.0 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | End of treatment, Little worsening (n=13,20) | 10.0 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | End of treatment, No change (n=13,20) | 45.0 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | End of treatment, Little improving (n=13,20) | 10.0 percentage of participants |
| Bevacizumab + Capecitabine | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category | End of treatment, Moderate Improving (n=13,20) | 5.0 percentage of participants |