A Study of Avastin (Bevacizumab) in Combination With Chemotherapy in Patients With Endocrine Tumors of the Gastrointestinal Tract.
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT00448136
Collaborator
(none)
83
27
2
52
3.1
0.1
Study Details
Study Description
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
- 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
83 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open Label Study to Evaluate the Effect of Avastin in Association With Chemotherapy on Progression-free Survival in Patients With Progressive Advanced/Metastatic Well-differentiated Digestive Endocrine Tumors of the Gastrointestinal Tract
Study Start Date
:
Jul 1, 2007
Actual Primary Completion Date
:
Nov 1, 2011
Actual Study Completion Date
:
Nov 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1
|
Drug: bevacizumab [Avastin]
7.5mg/kg iv on day 1 every 3 weeks
Drug: 5 FU
400mg/m2/day iv on days 1-5 every 6 weeks
Drug: Streptozotocin
500mg/m2/day iv on days 1-5 every 6 weeks
|
| Experimental: 2
|
Drug: bevacizumab [Avastin]
7.5mg/kg iv on day 1 every 3 weeks
Drug: Xeloda
1000mg/m2 po bid on days 1-14 every 3 weeks
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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.
- 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts 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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Angers | France | 49933 | ||
| 2 | Bordeaux | France | 33075 | ||
| 3 | Boulogne Billancourt | France | 92104 | ||
| 4 | Caen | France | 14033 | ||
| 5 | Chambray Les Tours | France | 37171 | ||
| 6 | Clichy | France | 92118 | ||
| 7 | Creteil | France | 94010 | ||
| 8 | Dijon | France | 21079 | ||
| 9 | Lille | France | 59020 | ||
| 10 | Lyon | France | 69437 | ||
| 11 | Marseille | France | 13273 | ||
| 12 | Marseille | France | 13285 | ||
| 13 | Marseille | France | 13385 | ||
| 14 | Montpellier | France | 34298 | ||
| 15 | Nantes | France | 44093 | ||
| 16 | Nice | France | 06189 | ||
| 17 | Paris | France | 75571 | ||
| 18 | Paris | France | 75651 | ||
| 19 | Paris | France | 75908 | ||
| 20 | Paris | France | 75970 | ||
| 21 | Poitiers | France | 86021 | ||
| 22 | Reims | France | 51092 | ||
| 23 | Rouen | France | 76031 | ||
| 24 | Saint Brieuc | France | 22015 | ||
| 25 | Strasbourg | France | 67091 | ||
| 26 | Toulouse | France | 31059 | ||
| 27 | Villejuif | France | 94805 |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00448136
Other Study ID Numbers:
- ML20383
First Posted:
Mar 16, 2007
Last Update Posted:
Jan 22, 2015
Last Verified:
Jan 1, 2015
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Bevacizumab + 5-fluorouracil (5-FU) + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | Cycles 1-5 (42-day cycles): Participants received bevacizumab 7.5 milligrams per kilogram (mg/kg) intravenously (IV) on Days 1 and 22; 5-FU 400 mg per square meter per day (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. | Cycles 1-9 (21-day cycles): Participants received bevacizumab 7.5 mg/kg IV on Day 1; capecitabine 1000 mg/m^2, tablets, orally (PO), twice daily (BID) on Days 1 through 14. Days 15-21 were a rest period. This 21-day cycle was repeated at least 8 times. |
| Period Title: Overall Study | ||
| STARTED | 34 | 49 |
| COMPLETED | 30 | 41 |
| NOT COMPLETED | 4 | 8 |
Baseline Characteristics
| Arm/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | Total of all reporting groups |
| Overall Participants | 34 | 49 | 83 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
55.93
(10.63)
|
61.64
(9.20)
|
59.29
(10.15)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
12
35.3%
|
23
46.9%
|
35
42.2%
|
| Male |
22
64.7%
|
26
53.1%
|
48
57.8%
|
Outcome Measures
| Title | Progression-Free Survival (PFS) - Percentage of Participants With an Event |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 34 | 49 |
| Number [percentage of participants] |
52.9
155.6%
|
53.1
108.4%
|
| Title | Percentage of Participants With a Response by Best Overall Response |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. Data were missing from centralized review for 1 participant. |
| Arm/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 34 | 49 |
| PR (Investigator) |
55.9
164.4%
|
18.4
37.6%
|
| PR (Centralized review) |
51.5
151.5%
|
12.5
25.5%
|
| SD (Investigator) |
44.1
129.7%
|
69.4
141.6%
|
| SD (Centralized review) |
48.5
142.6%
|
81.3
165.9%
|
| PD (Investigator) |
0
0%
|
8.2
16.7%
|
| PD (Centralized review) |
0
0%
|
0
0%
|
| Not evaluable (Investigator) |
0
0%
|
4.1
8.4%
|
| Not evaluable (Centralized review) |
0
0%
|
6.3
12.9%
|
| Title | Duration of Overall Response (OR) - Percentage of Participants With an Event |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population; only participants with a response of CR or PR were included in the analysis. |
| Arm/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 19 | 9 |
| Number [percentage of participants] |
42.1
123.8%
|
22.2
45.3%
|
| Title | PFS - Time to Event |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 34 | 49 |
| Median (95% Confidence Interval) [months] |
23.7
|
23.4
|
| Title | PFS - Percentage of Participants Estimated to be Progression Free at 12 and 24 Months |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 34 | 49 |
| 12 months |
76
223.5%
|
65
132.7%
|
| 24 months |
50
147.1%
|
48
98%
|
| Title | Duration of OR - Time to Event |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population; only participants with a response of CR or PR were included in the analysis. |
| Arm/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 19 | 9 |
| Median (95% Confidence Interval) [months] |
NA
|
NA
|
| Title | Duration of OR - Percentage of Participants With Sustained Response at 12 and 24 Months |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 19 | 9 |
| 12 months |
74
217.6%
|
70
142.9%
|
| 24 months |
55
161.8%
|
NA
NaN
|
| Title | Duration of Overall Disease Control (ODC) - Percentage of Participants With an Event |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 34 | 43 |
| Number [percentage of participants] |
52.9
155.6%
|
46.5
94.9%
|
| Title | Duration of ODC - Time to Event |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population; only participants with a response (CR, PR, or SD) were included in the analysis. |
| Arm/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 34 | 43 |
| Median (95% Confidence Interval) [months] |
22.3
|
23.4
|
| Title | Duration of ODC - Percentage of Participants Maintaining Disease Control at 12 and 24 Months |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population; only participants with a response (CR, PR, or SD) were included in the analysis. |
| Arm/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 34 | 43 |
| 12 months |
68
200%
|
72
146.9%
|
| 24 months |
42
123.5%
|
NA
NaN
|
| Title | Overall Survival (OS) - Percentage of Participants With an Event |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 34 | 49 |
| Number [percentage of participants] |
14.7
43.2%
|
16.3
33.3%
|
| Title | OS - Time to Event |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population |
| Arm/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 34 | 49 |
| Median (95% Confidence Interval) [months] |
NA
|
NA
|
| Title | OS - Percentage of Participants Surviving at 12 and 24 Months |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. |
| Arm/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 34 | 49 |
| 12 months |
94
276.5%
|
88
179.6%
|
| 24 months |
88
258.8%
|
85
173.5%
|
| Title | Global Health Status as Assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 29 | 40 |
| Baseline (n=29,40) |
65.23
(23.89)
|
65.42
(20.02)
|
| 3 months (n=20,32) |
65.83
(19.48)
|
57.03
(22.41)
|
| 6 months (n=20,24) |
60.00
(21.90)
|
66.32
(21.35)
|
| 12 months (n=13,14) |
66.03
(17.83)
|
72.62
(19.46)
|
| End of treatment (n=13,23) |
64.74
(23.36)
|
57.97
(28.48)
|
| Title | Percentage of Participants With Change From Baseline in Global Health Status by EORTC QLQ-C30 Improvement Category |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 20 | 29 |
| 3 months, Very much worsening (n=20,29) |
10.0
29.4%
|
17.2
35.1%
|
| 3 months, Moderate worsening (n=20,29) |
10.0
29.4%
|
24.1
49.2%
|
| 3 months, Little worsening (n=20,29) |
10.0
29.4%
|
17.2
35.1%
|
| 3 months, No change (n=20,29) |
40.0
117.6%
|
24.1
49.2%
|
| 3 months, Little improving (n=20,29) |
5.0
14.7%
|
3.4
6.9%
|
| 3 months, Moderate Improving (n=20,29) |
15.0
44.1%
|
3.4
6.9%
|
| 3 months, Very much improving (n=20,29) |
10.0
29.4%
|
10.3
21%
|
| 6 months, Very much worsening (n=20,22) |
15.0
44.1%
|
22.7
46.3%
|
| 6 months, Moderate worsening (n=20,22) |
10.0
29.4%
|
18.2
37.1%
|
| 6 months, Little worsening (n=20,22) |
5.0
14.7%
|
0
0%
|
| 6 months, No change (n=20,22) |
35.0
102.9%
|
31.8
64.9%
|
| 6 months, Little improving (n=20,22) |
10.0
29.4%
|
13.6
27.8%
|
| 6 months, Moderate Improving (n=20,22) |
15.0
44.1%
|
0
0%
|
| 6 months, Very much improving (n=20,22) |
10.0
29.4%
|
13.6
27.8%
|
| 12 months, Very much worsening (n=12,13) |
8.3
24.4%
|
0
0%
|
| 12 months, Moderate worsening (n=12,13) |
8.3
24.4%
|
15.4
31.4%
|
| 12 months - Little worsening (n=12,13) |
33.3
97.9%
|
15.4
31.4%
|
| 12 months, No change (n=12,13) |
25.0
73.5%
|
38.5
78.6%
|
| 12 months, Little improving (n=12,13) |
8.3
24.4%
|
7.7
15.7%
|
| 12 months, Moderate Improving (n=12,13) |
16.7
49.1%
|
15.4
31.4%
|
| 12 months, Very much improving (n=12,13) |
0
0%
|
7.7
15.7%
|
| End of treatment, Very much worsening (n=13,20) |
15.4
45.3%
|
15.0
30.6%
|
| End of treatment, Moderate worsening (n=13,20) |
30.8
90.6%
|
5.0
10.2%
|
| End of treatment, Little worsening (n=13,20) |
0
0%
|
10.0
20.4%
|
| End of treatment, No change (n=13,20) |
15.4
45.3%
|
45.0
91.8%
|
| End of treatment, Little improving (n=13,20) |
15.4
45.3%
|
10.0
20.4%
|
| End of treatment, Moderate Improving (n=13,20) |
15.4
45.3%
|
5.0
10.2%
|
| End of treatment, Very much improving (n=13,20) |
7.7
22.6%
|
10.0
20.4%
|
| Title | EORTC QLQ-C30 Functional and Symptom Scale Scores |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 30 | 43 |
| Physical functioning, Baseline (n=30,43) |
90.44
(13.30)
|
87.71
(14.88)
|
| Physical functioning, 3 months (n=22,33) |
89.32
(12.77)
|
75.35
(24.07)
|
| Physical functioning, 6 months (n=21,24) |
81.98
(19.75)
|
82.50
(18.21)
|
| Physical functioning, End of Treatment (n=13,24) |
82.82
(20.21)
|
79.44
(19.85)
|
| Role functioning, Baseline (n=30,43) |
82.22
(27.31)
|
83.33
(25.46)
|
| Role functioning, 3 months (n=22,33) |
85.61
(21.39)
|
62.12
(33.66)
|
| Role functioning, 6 months (n=21,24) |
75.40
(29.16)
|
70.83
(28.34)
|
| Role functioning, End of Treatment (n=13,24) |
78.21
(32.90)
|
72.92
(29.00)
|
| Emotional functioning, Baseline (n=30,42) |
71.94
(28.32)
|
71.89
(20.50)
|
| Emotional functioning, 3 months (n=21,33) |
81.48
(20.53)
|
76.01
(24.27)
|
| Emotional functioning, 6 months (n=21,24) |
72.62
(28.28)
|
76.04
(26.27)
|
| Emotional functioning, End of Treatment (n=13,24) |
77.56
(23.17)
|
73.61
(24.04)
|
| Cognitive functioning, Baseline (n=30,42) |
86.67
(18.26)
|
87.30
(16.38)
|
| Cognitive functioning, 3 months (n=22,33) |
89.39
(15.04)
|
83.84
(21.03)
|
| Cognitive functioning, 6 months (n=21,24) |
83.33
(21.08)
|
82.64
(18.04)
|
| Cognitive functioning, End of Treatment (n=13,24) |
83.33
(22.57)
|
81.94
(25.97)
|
| Social functioning, Baseline (n=30,41) |
86.11
(21.48)
|
87.40
(20.34)
|
| Social functioning, 3 months (n=22,33) |
89.39
(17.48)
|
75.76
(27.35)
|
| Social functioning, 6 months (n=21,24) |
81.75
(26.30)
|
83.33
(21.42)
|
| Social functioning, End of Treatment (n=13,24) |
84.62
(24.96)
|
81.94
(21.93)
|
| Fatigue, Baseline (n=30,42) |
26.30
(23.61)
|
27.25
(21.70)
|
| Fatigue, 3 months (n=21,33) |
27.78
(23.70)
|
43.10
(31.76)
|
| Fatigue, 6 months (n=20,24) |
36.67
(29.09)
|
37.96
(23.61)
|
| Fatigue, End of Treatment (n=13,24) |
34.19
(28.85)
|
34.49
(32.93)
|
| Nausea and vomiting, Baseline (n=30,42) |
6.67
(14.91)
|
2.78
(7.29)
|
| Nausea and vomiting, 3 months (n=22,33) |
10.61
(14.13)
|
9.60
(16.15)
|
| Nausea and vomiting, 6 months (n=21,24) |
8.73
(17.97)
|
7.64
(12.98)
|
| Nausea and vomiting, End of Treatment (n=13,24) |
10.26
(19.88)
|
6.25
(14.59)
|
| Pain, Baseline (n=30,43) |
14.44
(19.44)
|
21.71
(27.83)
|
| Pain, 3 months (n=22,33) |
12.88
(18.50)
|
18.18
(25.47)
|
| Pain, 6 months (n=21,24) |
23.02
(31.83)
|
17.36
(19.95)
|
| Pain, End of Treatment (n=13,24) |
20.51
(28.18)
|
26.39
(32.94)
|
| Dyspnea, Baseline (n=30,43) |
16.67
(25.89)
|
16.28
(25.59)
|
| Dyspnea, 3 months (n=21,33) |
12.70
(19.65)
|
30.30
(32.66)
|
| Dyspnea, 6 months (n=21,23) |
19.05
(24.88)
|
23.19
(29.19)
|
| Dyspnea, End of Treatment (n=13,24) |
20.51
(28.99)
|
23.61
(30.26)
|
| Insomnia, Baseline (n=30,43) |
24.44
(27.59)
|
24.03
(24.48)
|
| Insomnia, 3 months (n=21,33) |
20.63
(22.30)
|
27.27
(30.57)
|
| Insomnia, 6 months (n=21,24) |
33.33
(34.96)
|
29.17
(30.00)
|
| Insomnia, End of Treatment (n=13,24) |
23.08
(25.04)
|
30.56
(33.93)
|
| Appetite loss, Baseline (n=29,42) |
12.64
(16.46)
|
8.73
(20.90)
|
| Appetite loss, 3 months (n=22,33) |
7.58
(14.30)
|
20.20
(24.92)
|
| Appetite loss, 6 months (n=21,24) |
15.87
(27.12)
|
25.00
(26.47)
|
| Appetite loss, End of Treatment (n=13,24) |
12.82
(28.99)
|
25.00
(32.97)
|
| Constipation, Baseline (n=27,40) |
4.94
(15.20)
|
10.00
(21.62)
|
| Constipation, 3 months (n=21,33) |
15.87
(27.12)
|
7.07
(18.18)
|
| Constipation, 6 months (n=21,23) |
17.46
(27.12)
|
11.59
(21.58)
|
| Constipation, End of Treatment (n=13,24) |
12.82
(21.68)
|
13.89
(25.85)
|
| Diarrhea, Baseline (n=30,41) |
13.33
(24.13)
|
37.40
(31.79)
|
| Diarrhea, 3 months (n=22,32) |
9.09
(21.04)
|
45.83
(34.65)
|
| Diarrhea, 6 months (n=21,23) |
6.35
(17.06)
|
43.48
(30.87)
|
| Diarrhea, End of Treatment (n=12,22) |
2.78
(9.62)
|
28.79
(31.36)
|
| Financial difficulties, Baseline (n=30,413) |
14.44
(25.80)
|
8.13
(17.92)
|
| Financial difficulties, 3 months (n=22,33) |
9.09
(15.19)
|
6.06
(15.49)
|
| Financial difficulties, 6 months (n=21,23) |
15.87
(24.99)
|
2.90
(9.60)
|
| Financial difficulties, End of treatment (n=13,24) |
17.95
(25.88)
|
4.17
(14.95)
|
Adverse Events
| Time Frame | Adverse events (AEs) were collected from the date of first dose of study medication until 28 days after the last dose of study medication. Related serious AEs and AEs of special interest (AESIs) were recorded during follow-up. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All participants who received at least 1 dose of study treatment were included in the safety population. A separate analysis of nonserious AEs was not performed, therefore the AEs presented in the other nonserious AE table include all AEs reported during the study, not just nonserious events. | |||
| Arm/Group Title | Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine | ||
| Arm/Group Description | 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. | Cycles 1-9 (21-Day cycle): Participants received bevacizumab 7.5 mg/kg IV on Day 1; capecitabine 2000 mg/m^2 tablets PO in a divided dose every 12 hours within 30 minutes following a meal, on Days 1 through 14. Days 15-21 were a rest period. This 21-day cycle was repeated at least 8 times. | ||
All Cause Mortality |
||||
| Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/34 (32.4%) | 13/49 (26.5%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile neutropenia | 0/34 (0%) | 1/49 (2%) | ||
| Cardiac disorders | ||||
| Cardiac failure | 0/34 (0%) | 1/49 (2%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/34 (0%) | 2/49 (4.1%) | ||
| Abdominal pain upper | 2/34 (5.9%) | 0/49 (0%) | ||
| Intestinal obstruction | 0/34 (0%) | 2/49 (4.1%) | ||
| Diarrhea | 0/34 (0%) | 1/49 (2%) | ||
| Gastrointestinal hemorrhage | 2/34 (5.9%) | 0/49 (0%) | ||
| Gastrointestinal perforation | 0/34 (0%) | 1/49 (2%) | ||
| General disorders | ||||
| Pyrexia | 3/34 (8.8%) | 0/49 (0%) | ||
| General physical health deterioration | 0/34 (0%) | 2/49 (4.1%) | ||
| Influenza like illness | 1/34 (2.9%) | 0/49 (0%) | ||
| Hemorrhage | 1/34 (2.9%) | 1/49 (2%) | ||
| Hepatobiliary disorders | ||||
| Jaundice | 1/34 (2.9%) | 0/49 (0%) | ||
| Immune system disorders | ||||
| Anaphylactic shock | 0/34 (0%) | 1/49 (2%) | ||
| Infections and infestations | ||||
| Post-procedural sepsis | 1/34 (2.9%) | 0/49 (0%) | ||
| Respiratory tract infection | 0/34 (0%) | 1/49 (2%) | ||
| Peritonitis | 0/34 (0%) | 1/49 (2%) | ||
| Injury, poisoning and procedural complications | ||||
| Chest injury | 0/34 (0%) | 1/49 (2%) | ||
| Wound | 0/34 (0%) | 1/49 (2%) | ||
| Metabolism and nutrition disorders | ||||
| Hypoglycaemia | 2/34 (5.9%) | 0/49 (0%) | ||
| Decreased appetite | 0/34 (0%) | 1/49 (2%) | ||
| Nervous system disorders | ||||
| Cerebrovascular accident | 1/34 (2.9%) | 0/49 (0%) | ||
| Cerebral ischaemia | 0/34 (0%) | 1/49 (2%) | ||
| Cerebral infarction | 0/34 (0%) | 1/49 (2%) | ||
| Hemorrhagic stroke | 0/34 (0%) | 1/49 (2%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pleural effusion | 1/34 (2.9%) | 0/49 (0%) | ||
| Pulmonary embolism | 1/34 (2.9%) | 0/49 (0%) | ||
| Vascular disorders | ||||
| Thrombotic microangiopathy | 1/34 (2.9%) | 0/49 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Bevacizumab + 5-FU + Streptozocin | Bevacizumab + Capecitabine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 34/34 (100%) | 49/49 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 4/34 (11.8%) | 7/49 (14.3%) | ||
| Neutropenia | 2/34 (5.9%) | 8/49 (16.3%) | ||
| Thrombocytopenia | 3/34 (8.8%) | 6/49 (12.2%) | ||
| Leukopenia | 1/34 (2.9%) | 5/49 (10.2%) | ||
| Lymphopenia | 2/34 (5.9%) | 4/49 (8.2%) | ||
| Febrile neutropenia | 0/34 (0%) | 1/49 (2%) | ||
| Cardiac disorders | ||||
| Tachycardia | 1/34 (2.9%) | 1/49 (2%) | ||
| Aortic valve incompetence | 0/34 (0%) | 1/49 (2%) | ||
| Cardiac disorder | 0/34 (0%) | 1/49 (2%) | ||
| Cardiac flutter | 0/34 (0%) | 1/49 (2%) | ||
| Cardiomyopathy | 0/34 (0%) | 1/49 (2%) | ||
| Non-obstructive cardiomyopathy | 0/34 (0%) | 1/49 (2%) | ||
| Palpitations | 0/34 (0%) | 1/49 (2%) | ||
| Sinus bradycardia | 0/34 (0%) | 1/49 (2%) | ||
| Ventricular extrasystoles | 0/34 (0%) | 1/49 (2%) | ||
| Ear and labyrinth disorders | ||||
| Hypoacusis | 1/34 (2.9%) | 1/49 (2%) | ||
| Tinnitus | 0/34 (0%) | 2/49 (4.1%) | ||
| Vertigo positional | 1/34 (2.9%) | 0/49 (0%) | ||
| Eye disorders | ||||
| Visual acuity reduced | 2/34 (5.9%) | 0/49 (0%) | ||
| Visual impairment | 1/34 (2.9%) | 1/49 (2%) | ||
| Conjunctivitis allergic | 1/34 (2.9%) | 0/49 (0%) | ||
| Dry eye | 0/34 (0%) | 1/49 (2%) | ||
| Eyelid oedema | 0/34 (0%) | 1/49 (2%) | ||
| Vision blurred | 0/34 (0%) | 1/49 (2%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 24/34 (70.6%) | 24/49 (49%) | ||
| Diarrhoea | 12/34 (35.3%) | 32/49 (65.3%) | ||
| Constipation | 19/34 (55.9%) | 9/49 (18.4%) | ||
| Abdominal pain | 13/34 (38.2%) | 12/49 (24.5%) | ||
| Abdominal pain upper | 11/34 (32.4%) | 11/49 (22.4%) | ||
| Vomiting | 11/34 (32.4%) | 7/49 (14.3%) | ||
| Haemorrhoids | 4/34 (11.8%) | 5/49 (10.2%) | ||
| Dry mouth | 4/34 (11.8%) | 4/49 (8.2%) | ||
| Aphthous stomatitis | 3/34 (8.8%) | 4/49 (8.2%) | ||
| Gastrooesophageal reflux disease | 5/34 (14.7%) | 2/49 (4.1%) | ||
| Stomatitis | 3/34 (8.8%) | 3/49 (6.1%) | ||
| Dyspepsia | 2/34 (5.9%) | 3/49 (6.1%) | ||
| Flatulence | 2/34 (5.9%) | 2/49 (4.1%) | ||
| Anal fissure | 1/34 (2.9%) | 2/49 (4.1%) | ||
| Intestinal obstruction | 0/34 (0%) | 3/49 (6.1%) | ||
| Proctalgia | 0/34 (0%) | 3/49 (6.1%) | ||
| Toothache | 0/34 (0%) | 3/49 (6.1%) | ||
| Abdominal distension | 1/34 (2.9%) | 1/49 (2%) | ||
| Abdominal pain lower | 1/34 (2.9%) | 1/49 (2%) | ||
| Anorectal discomfort | 0/34 (0%) | 2/49 (4.1%) | ||
| Dysphagia | 0/34 (0%) | 2/49 (4.1%) | ||
| Gingival bleeding | 1/34 (2.9%) | 1/49 (2%) | ||
| Loose tooth | 1/34 (2.9%) | 1/49 (2%) | ||
| Abdominal discomfort | 0/34 (0%) | 2/49 (4.1%) | ||
| Abdominal rigidity | 0/34 (0%) | 1/49 (2%) | ||
| Faeces discoloured | 0/34 (0%) | 1/49 (2%) | ||
| Gastritis | 1/34 (2.9%) | 0/49 (0%) | ||
| Gastrointestinal motility disorder | 0/34 (0%) | 1/49 (2%) | ||
| Lip swelling | 0/34 (0%) | 1/49 (2%) | ||
| Proctitis | 0/34 (0%) | 1/49 (2%) | ||
| Salivary hypersecretion | 1/34 (2.9%) | 0/49 (0%) | ||
| Steatorrhoea | 1/34 (2.9%) | 0/49 (0%) | ||
| Tongue discolouration | 0/34 (0%) | 1/49 (2%) | ||
| Tongue haematoma | 1/34 (2.9%) | 0/49 (0%) | ||
| Varices oesophageal | 0/34 (0%) | 1/49 (2%) | ||
| General disorders | ||||
| Asthenia | 23/34 (67.6%) | 28/49 (57.1%) | ||
| Mucosal inflammation | 14/34 (41.2%) | 17/49 (34.7%) | ||
| Oedema peripheral | 4/34 (11.8%) | 9/49 (18.4%) | ||
| Pyrexia | 8/34 (23.5%) | 4/49 (8.2%) | ||
| Fatigue | 4/34 (11.8%) | 5/49 (10.2%) | ||
| Xerosis | 1/34 (2.9%) | 3/49 (6.1%) | ||
| Chest pain | 1/34 (2.9%) | 2/49 (4.1%) | ||
| Chills | 3/34 (8.8%) | 0/49 (0%) | ||
| General physical health deterioration | 0/34 (0%) | 3/49 (6.1%) | ||
| Influenza like illness | 3/34 (8.8%) | 0/49 (0%) | ||
| Malaise | 0/34 (0%) | 2/49 (4.1%) | ||
| Oedema | 2/34 (5.9%) | 0/49 (0%) | ||
| Catheter site haematoma | 1/34 (2.9%) | 0/49 (0%) | ||
| Catheter site pain | 1/34 (2.9%) | 0/49 (0%) | ||
| Drug intolerance | 0/34 (0%) | 1/49 (2%) | ||
| Face oedema | 0/34 (0%) | 1/49 (2%) | ||
| Implant site inflammation | 0/34 (0%) | 1/49 (2%) | ||
| Injection site pain | 0/34 (0%) | 1/49 (2%) | ||
| Mucosal dryness | 0/34 (0%) | 1/49 (2%) | ||
| Pain | 1/34 (2.9%) | 0/49 (0%) | ||
| Hepatobiliary disorders | ||||
| Portal hypertension | 2/34 (5.9%) | 1/49 (2%) | ||
| Cytolytic hepatitis | 2/34 (5.9%) | 0/49 (0%) | ||
| Biliary colic | 0/34 (0%) | 1/49 (2%) | ||
| Cholestasis | 0/34 (0%) | 1/49 (2%) | ||
| Hepatic pain | 0/34 (0%) | 1/49 (2%) | ||
| Jaundice | 1/34 (2.9%) | 0/49 (0%) | ||
| Immune system disorders | ||||
| Anaphylactic shock | 0/34 (0%) | 1/49 (2%) | ||
| Infections and infestations | ||||
| Nasopharyngitis | 4/34 (11.8%) | 4/49 (8.2%) | ||
| Bronchitis | 3/34 (8.8%) | 3/49 (6.1%) | ||
| Gastroenteritis | 2/34 (5.9%) | 4/49 (8.2%) | ||
| Pharyngitis | 2/34 (5.9%) | 4/49 (8.2%) | ||
| Urinary tract infection | 2/34 (5.9%) | 4/49 (8.2%) | ||
| Sinusitis | 2/34 (5.9%) | 2/49 (4.1%) | ||
| Tonsillitis | 3/34 (8.8%) | 1/49 (2%) | ||
| Cystitis | 1/34 (2.9%) | 2/49 (4.1%) | ||
| Herpes simplex | 1/34 (2.9%) | 2/49 (4.1%) | ||
| Infection | 1/34 (2.9%) | 2/49 (4.1%) | ||
| Oral herpes | 2/34 (5.9%) | 1/49 (2%) | ||
| Tooth abscess | 1/34 (2.9%) | 2/49 (4.1%) | ||
| Injection site infection | 1/34 (2.9%) | 1/49 (2%) | ||
| Rhinitis | 0/34 (0%) | 2/49 (4.1%) | ||
| Tooth infection | 0/34 (0%) | 2/49 (4.1%) | ||
| Candidiasis | 0/34 (0%) | 1/49 (2%) | ||
| Cholecystitis infective | 1/34 (2.9%) | 0/49 (0%) | ||
| Chronic sinusitis | 0/34 (0%) | 1/49 (2%) | ||
| Erysipelas | 0/34 (0%) | 1/49 (2%) | ||
| Folliculitis | 0/34 (0%) | 1/49 (2%) | ||
| Fungal infection | 0/34 (0%) | 1/49 (2%) | ||
| Gastroenteritis escherichia coli | 0/34 (0%) | 1/49 (2%) | ||
| Gastroenteritis viral | 0/34 (0%) | 1/49 (2%) | ||
| Herpes zoster ophthalmic | 0/34 (0%) | 1/49 (2%) | ||
| Hordeolum | 1/34 (2.9%) | 0/49 (0%) | ||
| Infected cyst | 1/34 (2.9%) | 0/49 (0%) | ||
| Laryngitis | 0/34 (0%) | 1/49 (2%) | ||
| Oral candidiasis | 0/34 (0%) | 1/49 (2%) | ||
| Post procedural sepsis | 1/34 (2.9%) | 0/49 (0%) | ||
| Respiratory tract infection | 0/34 (0%) | 1/49 (2%) | ||
| Staphylococcal infection | 0/34 (0%) | 1/49 (2%) | ||
| Tracheobronchitis | 1/34 (2.9%) | 0/49 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Wound | 0/34 (0%) | 2/49 (4.1%) | ||
| Ankle fracture | 1/34 (2.9%) | 0/49 (0%) | ||
| Bite | 0/34 (0%) | 1/49 (2%) | ||
| Burn of internal organs | 0/34 (0%) | 1/49 (2%) | ||
| Chest injury | 0/34 (0%) | 1/49 (2%) | ||
| Contusion | 1/34 (2.9%) | 0/49 (0%) | ||
| Fall | 0/34 (0%) | 1/49 (2%) | ||
| Fibula fracture | 0/34 (0%) | 1/49 (2%) | ||
| Frostbite | 1/34 (2.9%) | 0/49 (0%) | ||
| Iatrogenic injury | 0/34 (0%) | 1/49 (2%) | ||
| Limb injury | 1/34 (2.9%) | 0/49 (0%) | ||
| Multiple fractures | 0/34 (0%) | 1/49 (2%) | ||
| Muscle strain | 0/34 (0%) | 1/49 (2%) | ||
| Radiation mucositis | 1/34 (2.9%) | 0/49 (0%) | ||
| Rib fracture | 1/34 (2.9%) | 1/49 (2%) | ||
| Investigations | ||||
| Weight decreased | 4/34 (11.8%) | 5/49 (10.2%) | ||
| Blood bilirubin abnormal | 0/34 (0%) | 2/49 (4.1%) | ||
| Activated partial thromboplastin time prolonged | 1/34 (2.9%) | 0/49 (0%) | ||
| Alanine aminotransferase abnormal | 1/34 (2.9%) | 0/49 (0%) | ||
| Alanine aminotransferase increased | 1/34 (2.9%) | 0/49 (0%) | ||
| Aspartate aminotransferase increased | 1/34 (2.9%) | 0/49 (0%) | ||
| Blood creatinine decreased | 1/34 (2.9%) | 0/49 (0%) | ||
| Blood creatinine increased | 1/34 (2.9%) | 0/49 (0%) | ||
| Cardiac murmur | 0/34 (0%) | 1/49 (2%) | ||
| Creatinine renal clearance decreased | 1/34 (2.9%) | 0/49 (0%) | ||
| Gamma-glutamyltransferase abnormal | 1/34 (2.9%) | 0/49 (0%) | ||
| Gamma-glutamyltransferase increased | 1/34 (2.9%) | 0/49 (0%) | ||
| Haemoglobin | 0/34 (0%) | 1/49 (2%) | ||
| Lipase increased | 1/34 (2.9%) | 0/49 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 5/34 (14.7%) | 6/49 (12.2%) | ||
| Hyperglycaemia | 3/34 (8.8%) | 4/49 (8.2%) | ||
| Anorexia | 2/34 (5.9%) | 2/49 (4.1%) | ||
| Hypokalaemia | 0/34 (0%) | 4/49 (8.2%) | ||
| Gout | 1/34 (2.9%) | 2/49 (4.1%) | ||
| Hypocalcaemia | 0/34 (0%) | 3/49 (6.1%) | ||
| Hypoglycaemia | 3/34 (8.8%) | 0/49 (0%) | ||
| Vitamin D deficiency | 2/34 (5.9%) | 0/49 (0%) | ||
| Dehydration | 0/34 (0%) | 1/49 (2%) | ||
| Diabetes mellitus inadequate control | 1/34 (2.9%) | 0/49 (0%) | ||
| Food intolerance | 0/34 (0%) | 1/49 (2%) | ||
| Hyperkalaemia | 0/34 (0%) | 1/49 (2%) | ||
| Hypertriglyceridaemia | 0/34 (0%) | 1/49 (2%) | ||
| Hypoglycaemic unconsciousness | 1/34 (2.9%) | 0/49 (0%) | ||
| Hyposideraemia | 1/34 (2.9%) | 0/49 (0%) | ||
| Iron deficiency | 0/34 (0%) | 1/49 (2%) | ||
| Malnutrition | 1/34 (2.9%) | 0/49 (0%) | ||
| Vitamin K deficiency | 0/34 (0%) | 1/49 (2%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 8/34 (23.5%) | 6/49 (12.2%) | ||
| Back pain | 6/34 (17.6%) | 4/49 (8.2%) | ||
| Musculoskeletal pain | 3/34 (8.8%) | 3/49 (6.1%) | ||
| Neck pain | 2/34 (5.9%) | 4/49 (8.2%) | ||
| Myalgia | 4/34 (11.8%) | 0/49 (0%) | ||
| Pain in extremity | 2/34 (5.9%) | 2/49 (4.1%) | ||
| Flank pain | 1/34 (2.9%) | 2/49 (4.1%) | ||
| Bone pain | 0/34 (0%) | 2/49 (4.1%) | ||
| Tendon disorder | 1/34 (2.9%) | 1/49 (2%) | ||
| Haemarthrosis | 1/34 (2.9%) | 0/49 (0%) | ||
| Muscle fatigue | 0/34 (0%) | 1/49 (2%) | ||
| Muscle spasms | 0/34 (0%) | 1/49 (2%) | ||
| Musculoskeletal chest pain | 0/34 (0%) | 1/49 (2%) | ||
| Osteoarthritis | 1/34 (2.9%) | 0/49 (0%) | ||
| Pain in jaw | 1/34 (2.9%) | 0/49 (0%) | ||
| Rheumatoid arthritis | 0/34 (0%) | 1/49 (2%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Neoplasm progression | 1/34 (2.9%) | 0/49 (0%) | ||
| Pyogenic granuloma | 0/34 (0%) | 1/49 (2%) | ||
| Skin papilloma | 1/34 (2.9%) | 0/49 (0%) | ||
| Nervous system disorders | ||||
| Headache | 13/34 (38.2%) | 14/49 (28.6%) | ||
| Paraesthesia | 4/34 (11.8%) | 4/49 (8.2%) | ||
| Dizziness | 3/34 (8.8%) | 4/49 (8.2%) | ||
| Dysgeusia | 0/34 (0%) | 4/49 (8.2%) | ||
| Dysaesthesia | 1/34 (2.9%) | 1/49 (2%) | ||
| Migraine | 0/34 (0%) | 2/49 (4.1%) | ||
| Neuropathy peripheral | 1/34 (2.9%) | 1/49 (2%) | ||
| Sciatica | 1/34 (2.9%) | 1/49 (2%) | ||
| Ageusia | 0/34 (0%) | 1/49 (2%) | ||
| Amnesia | 1/34 (2.9%) | 0/49 (0%) | ||
| Balance disorder | 0/34 (0%) | 1/49 (2%) | ||
| Burning sensation | 1/34 (2.9%) | 0/49 (0%) | ||
| Epilepsy | 1/34 (2.9%) | 0/49 (0%) | ||
| Hypokinesia | 1/34 (2.9%) | 0/49 (0%) | ||
| Loss of consciousness | 1/34 (2.9%) | 0/49 (0%) | ||
| Parkinson's disease | 0/34 (0%) | 1/49 (2%) | ||
| Presyncope | 0/34 (0%) | 1/49 (2%) | ||
| Sensory disturbance | 1/34 (2.9%) | 0/49 (0%) | ||
| Transient ischaemic attack | 1/34 (2.9%) | 0/49 (0%) | ||
| Tremor | 0/34 (0%) | 1/49 (2%) | ||
| Psychiatric disorders | ||||
| Anxiety | 6/34 (17.6%) | 6/49 (12.2%) | ||
| Insomnia | 4/34 (11.8%) | 5/49 (10.2%) | ||
| Depression | 1/34 (2.9%) | 3/49 (6.1%) | ||
| Confusional state | 0/34 (0%) | 3/49 (6.1%) | ||
| Sleep disorder | 0/34 (0%) | 2/49 (4.1%) | ||
| Stress | 0/34 (0%) | 1/49 (2%) | ||
| Renal and urinary disorders | ||||
| Glycosuria | 0/34 (0%) | 3/49 (6.1%) | ||
| Dysuria | 1/34 (2.9%) | 1/49 (2%) | ||
| Renal failure | 2/34 (5.9%) | 0/49 (0%) | ||
| Albuminuria | 0/34 (0%) | 1/49 (2%) | ||
| Leukocyturia | 0/34 (0%) | 1/49 (2%) | ||
| Polyuria | 0/34 (0%) | 1/49 (2%) | ||
| Urinary incontinence | 0/34 (0%) | 1/49 (2%) | ||
| Reproductive system and breast disorders | ||||
| Epididymitis | 0/34 (0%) | 1/49 (2%) | ||
| Erosive balanitis | 0/34 (0%) | 1/49 (2%) | ||
| Metrorrhagia | 0/34 (0%) | 1/49 (2%) | ||
| Testicular pain | 0/34 (0%) | 1/49 (2%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 3/34 (8.8%) | 5/49 (10.2%) | ||
| Dyspnoea | 2/34 (5.9%) | 2/49 (4.1%) | ||
| Rhinorrhoea | 2/34 (5.9%) | 2/49 (4.1%) | ||
| Dysphonia | 1/34 (2.9%) | 2/49 (4.1%) | ||
| Dyspnoea extertional | 1/34 (2.9%) | 2/49 (4.1%) | ||
| Pleural effusion | 1/34 (2.9%) | 1/49 (2%) | ||
| Nasal dryness | 1/34 (2.9%) | 0/49 (0%) | ||
| Pneumonia aspiration | 0/34 (0%) | 1/49 (2%) | ||
| Sleep apnoea syndrome | 0/34 (0%) | 1/49 (2%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Palmar-plantar erythrodysaesthesia syndrome | 6/34 (17.6%) | 31/49 (63.3%) | ||
| Pruritus | 5/34 (14.7%) | 7/49 (14.3%) | ||
| Dry skin | 3/34 (8.8%) | 8/49 (16.3%) | ||
| Erythema | 3/34 (8.8%) | 4/49 (8.2%) | ||
| Rash | 3/34 (8.8%) | 1/49 (2%) | ||
| Alopecia | 2/34 (5.9%) | 1/49 (2%) | ||
| Acne | 1/34 (2.9%) | 1/49 (2%) | ||
| Angioedema | 1/34 (2.9%) | 1/49 (2%) | ||
| Hyperkeratosis palmaris and plantaris | 1/34 (2.9%) | 1/49 (2%) | ||
| Petechiae | 0/34 (0%) | 2/49 (4.1%) | ||
| Pigmentation disorder | 0/34 (0%) | 2/49 (4.1%) | ||
| Skin hyperpigmentation | 0/34 (0%) | 2/49 (4.1%) | ||
| Skin lesion | 1/34 (2.9%) | 1/49 (2%) | ||
| Urticaria | 1/34 (2.9%) | 1/49 (2%) | ||
| Dermatitis | 0/34 (0%) | 1/49 (2%) | ||
| Dyshidrosis | 0/34 (0%) | 1/49 (2%) | ||
| Nail discomfort | 0/34 (0%) | 1/49 (2%) | ||
| Nail disorder | 0/34 (0%) | 1/49 (2%) | ||
| Nail toxicity | 0/34 (0%) | 1/49 (2%) | ||
| Night sweats | 0/34 (0%) | 1/49 (2%) | ||
| Onychoclasis | 0/34 (0%) | 1/49 (2%) | ||
| Photosensitivity reaction | 0/34 (0%) | 1/49 (2%) | ||
| Purpura | 0/34 (0%) | 1/49 (2%) | ||
| Skin chapped | 0/34 (0%) | 1/49 (2%) | ||
| Skin discolouration | 1/34 (2.9%) | 0/49 (0%) | ||
| Skin fissures | 0/34 (0%) | 1/49 (2%) | ||
| Skin reaction | 1/34 (2.9%) | 0/49 (0%) | ||
| Skin toxicity | 0/34 (0%) | 1/49 (2%) | ||
| Spider naevus | 0/34 (0%) | 1/49 (2%) | ||
| Vascular disorders | ||||
| Flushing | 2/34 (5.9%) | 9/49 (18.4%) | ||
| Hot flush | 3/34 (8.8%) | 1/49 (2%) | ||
| Hypotension | 0/34 (0%) | 2/49 (4.1%) | ||
| Haematoma | 0/34 (0%) | 1/49 (2%) | ||
| Varicose vein | 1/34 (2.9%) | 0/49 (0%) | ||
| Vein discolouration | 0/34 (0%) | 1/49 (2%) | ||
| Venous insufficiency | 0/34 (0%) | 1/49 (2%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request the Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
| Name/Title | Medical Communications |
|---|---|
| Organization | Hoffmann-LaRoche |
| Phone | 800-821-8590 |
| genentech@druginfo.com |
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00448136
Other Study ID Numbers:
- ML20383
First Posted:
Mar 16, 2007
Last Update Posted:
Jan 22, 2015
Last Verified:
Jan 1, 2015