A Study of Avastin (Bevacizumab) Added to a Chemotherapeutic Regimen in Patients With Metastatic Pancreatic Cancer
Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT01214720
Collaborator
(none)
607
101
1
39
6
0.2
Study Details
Study Description
Brief Summary
This study will evaluate efficacy, safety and tolerability of Avastin versus placebo added to a chemotherapeutic regimen in patients with metastatic pancreatic cancer. The anticipated time of study treatment is until confirmed evidence of disease progression, and the target sample size is 500+ individuals.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
607 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind Study of the Effect of Avastin Plus Gemcitabine and Erlotinib Compared With Placebo Plus Gemcitabine and Erlotinib on Overall Survival in Patients With Metastatic Pancreatic Cancer
Study Start Date
:
Jul 1, 2005
Actual Primary Completion Date
:
Oct 1, 2008
Actual Study Completion Date
:
Oct 1, 2008
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1
|
Drug: bevacizumab [Avastin]
Intervenous repeating dose
|
Outcome Measures
Primary Outcome Measures
- Duration of Overall Survival - Percentage of Participants With an Event [Randomization, Weeks 1-8 of Cycle 1, Weeks 1-3 of consecutive cycles, 28 days and 3 months after lst treatment, and every 3 months for up to 18 months from last participant randomized]
Duration of overall survival (OS) was defined as the time between date of randomization and date of death due to any cause. Participants without an event were censored at the date last known to be alive. Participants who were randomized but not exposed to study drug and had no further follow up were censored at the date of randomization.
- Duration of Overall Survival - Time to Event [Randomization, Weeks 1-8 of Cycle 1, Weeks 1-3 of consecutive cycles, 28 days and 3 months after lst treatment, and every 3 months for up to 18 months from last participant randomized]
Duration of OS was defined as the time between date of randomization and date of death due to any cause. Participants without an event were censored at the date last known to be alive. Participants who were randomized but not exposed to study drug and had no further follow up were censored at the date of randomization. Median duration of survival was estimated using the Kaplan-Meier method.
Secondary Outcome Measures
- Clinical Benefit Response (CBR) [Randomization, Weeks 1-8 of Cycle 1, Weeks 1-3 of consecutive cycles, 28 days and 3 months after lst treatment, and every 3 months for up to 18 months from last participant randomized]
- Progression-Free Survival (PFS) - Percentage of Participants With an Event [Screening, Weeks 8, 16, 24, 32, 40, and every 12 weeks thereafter or until confirmed evidence of disease progression]
PFS was defined as the time between the date of randomization and the date of documented progressive disease (PD) defined according to modified Response Evaluation Criteria in Solid Tumors (RECIST) evaluation, or date of death due to any cause. PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum (LD) recorded since the treatment started. Participants without an event were censored at the date of last follow up for progression, or date of last available tumor assessment if no further follow up assessment for progression was performed. Participants who were randomized but not exposed to study drug and had no further follow up were censored at the date of randomization.
- Progression-Free Survival (PFS) - Time to Event [Screening, Weeks 8, 16, 24, 32, 40, and every 12 weeks thereafter or until confirmed evidence of disease progression]
PFS was defined as the time between the date of randomization and the date of documented PD (per RECIST), or date of death due to any cause. Data for participants without an event were censored at the date of last follow up for progression, or date of last available tumor assessment if no further follow up assessment for progression was performed. Participants who were randomized but not exposed to study drug and had no further follow up were censored at the date of randomization. Median PFS was estimated using the Kaplan-Meier method.
- Percentage of Participants With Complete Response (CR), Partial Response (PR), or Stable Disease (SD) at First Postbaseline Tumor Assessment [Baseline and Week 8]
Percentage of participants with CR, PR, or SD according to modified RECIST evaluation at the first postbaseline tumor assessment. CR equaled (=) complete disappearance of all target lesions and non-target disease, with normalization of tumor marker level. PR is greater than or equal to (≥) a 30% decrease of the sum of the LD of all target lesions as referenced to the baseline sum LD of all target lesions. Persistence of one or more non-target lesions(s) and/or maintenance of tumor marker level above normal limits. SD=neither sufficient shrinkage of target lesions to qualify for PR nor sufficient increase to qualify for PD with persistence of one or more non-target lesions(s) and/or maintenance of tumor marker level above normal limits.
- Bevacizumab Concentration in the Presence of Gemcitabine and Erlotinib [Weeks 1, 3, 5, 7, and 9]
Blood samples were collected from a subgroup of participants, in selected centers for the determination of bevacizumab serum concentration before the first bevacizumab/placebo exposure (Week 1) and at Weeks 3, 5, 7, and 9. Each time blood samples were collected just (preferably within 1 hour) before the start of the study treatment.
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;
-
metastatic pancreatic cancer (adenocarcinoma);
-
good liver, kidney, and bone marrow function.
Exclusion Criteria:
-
previous systemic treatment for metastatic pancreatic cancer;
-
pregnant or lactating females;
-
fertile men, or women of childbearing potential, not using adequate contraception;
-
major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start;
-
current or recent treatment (within 30 days prior to starting study treatment) with another investigational drug, or participation in another investigational study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Adelaide | Australia | 5011 | ||
| 2 | Camperdown | Australia | 2050 | ||
| 3 | Footscray | Australia | 3011 | ||
| 4 | Heidelberg | Australia | 3084 | ||
| 5 | Kurralta Park | Australia | 5037 | ||
| 6 | Melbourne | Australia | 3002 | ||
| 7 | Melbourne | Australia | 3128 | ||
| 8 | St. Leonards | Australia | 2065 | ||
| 9 | Sydney | Australia | 2031 | ||
| 10 | Sydney | Australia | 2217 | ||
| 11 | Graz | Austria | 8036 | ||
| 12 | Innsbruck | Austria | 6020 | ||
| 13 | Salzburg | Austria | 5020 | ||
| 14 | Wien | Austria | 1090 | ||
| 15 | Antwerpen | Belgium | 2020 | ||
| 16 | Bruxelles | Belgium | 1070 | ||
| 17 | Bruxelles | Belgium | 1200 | ||
| 18 | Leuven | Belgium | 3000 | ||
| 19 | Wilrijk | Belgium | 2610 | ||
| 20 | Edmonton | Alberta | Canada | T6G 1Z2 | |
| 21 | Vancouver | British Columbia | Canada | V5Z 4E6 | |
| 22 | Ottawa | Ontario | Canada | K1H 8L6 | |
| 23 | Toronto | Ontario | Canada | M5G 2M9 | |
| 24 | Montreal | Quebec | Canada | H2W 1S6 | |
| 25 | Quebec City | Quebec | Canada | G1R 2J6 | |
| 26 | Beijing | China | 100036 | ||
| 27 | Beijing | China | 100071 | ||
| 28 | Shanghai | China | 200433 | ||
| 29 | Brno | Czech Republic | 656 53 | ||
| 30 | Hradec Kralove | Czech Republic | 500 05 | ||
| 31 | Helsinki | Finland | 00029 | ||
| 32 | Besancon | France | 25030 | ||
| 33 | Bordeaux | France | 33000 | ||
| 34 | Boulogne-billancourt | France | 92104 | ||
| 35 | Clichy | France | 92118 | ||
| 36 | Limoges | France | 87042 | ||
| 37 | Marseille | France | 13273 | ||
| 38 | Paris | France | 75674 | ||
| 39 | Paris | France | 75679 | ||
| 40 | Rouen | France | 76031 | ||
| 41 | Saint Herblain | France | 44805 | ||
| 42 | Strasbourg | France | 67091 | ||
| 43 | Berlin | Germany | 13353 | ||
| 44 | Bochum | Germany | 44892 | ||
| 45 | Bonn | Germany | 53127 | ||
| 46 | Halle | Germany | 06120 | ||
| 47 | Hamburg | Germany | 20249 | ||
| 48 | Heidelberg | Germany | 69120 | ||
| 49 | Leipzig | Germany | 04103 | ||
| 50 | Magdeburg | Germany | 39130 | ||
| 51 | Mainz | Germany | 55101 | ||
| 52 | Muenchen | Germany | 81377 | ||
| 53 | Mönchengladbach | Germany | 41061 | ||
| 54 | Trier | Germany | 54290 | ||
| 55 | Kfar Saba | Israel | 44281 | ||
| 56 | Petach Tikva | Israel | 49100 | ||
| 57 | Rehovot | Israel | 76100 | ||
| 58 | Tel Aviv | Israel | 6423906 | ||
| 59 | Bergamo | Italy | 24128 | ||
| 60 | Bologna | Italy | 40138 | ||
| 61 | Brescia | Italy | 25124 | ||
| 62 | Chieti | Italy | 66100 | ||
| 63 | Genova | Italy | 16132 | ||
| 64 | Napoli | Italy | 80131 | ||
| 65 | Orbassano | Italy | 10043 | ||
| 66 | Parma | Italy | 43100 | ||
| 67 | San Giovanni Rotondo | Italy | 71013 | ||
| 68 | Amsterdam | Netherlands | 1105 AZ | ||
| 69 | Auckland | New Zealand | 1009 | ||
| 70 | Christchurch | New Zealand | |||
| 71 | Lima | Peru | 11 | ||
| 72 | Lima | Peru | 18 | ||
| 73 | Gliwice | Poland | 44-101 | ||
| 74 | Lublin | Poland | 20-081 | ||
| 75 | Szczecin | Poland | 71-730 | ||
| 76 | Wroclaw | Poland | 53-413 | ||
| 77 | Singapore | Singapore | 119228 | ||
| 78 | Singapore | Singapore | 169610 | ||
| 79 | Cape Town | South Africa | 7506 | ||
| 80 | Pretoria | South Africa | 0001 | ||
| 81 | Alicante | Spain | 03010 | ||
| 82 | Barcelona | Spain | 08035 | ||
| 83 | Barcelona | Spain | 08036 | ||
| 84 | Barcelona | Spain | 08041 | ||
| 85 | Barcelona | Spain | 08907 | ||
| 86 | Cordoba | Spain | 14004 | ||
| 87 | Elche | Spain | 03203 | ||
| 88 | Madrid | Spain | 28040 | ||
| 89 | Santander | Spain | 39008 | ||
| 90 | Valencia | Spain | 46009 | ||
| 91 | Valencia | Spain | 46010 | ||
| 92 | Stockholm | Sweden | 11883 | ||
| 93 | Kueishan | Taiwan | 333 | ||
| 94 | Taipei | Taiwan | 00112 | ||
| 95 | Glasgow | United Kingdom | G11 6NT | ||
| 96 | Leicester | United Kingdom | LE1 5WW | ||
| 97 | London | United Kingdom | SW3 6JJ | ||
| 98 | Manchester | United Kingdom | M20 4BX | ||
| 99 | Northwood | United Kingdom | HA6 2RN | ||
| 100 | Sutton | United Kingdom | SM2 5PT | ||
| 101 | Truro | United Kingdom | TR1 3LJ |
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:
NCT01214720
Other Study ID Numbers:
- BO17706
First Posted:
Oct 5, 2010
Last Update Posted:
Aug 13, 2014
Last Verified:
Jul 1, 2014
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Bevacizumab + Gemcitabine + Erlotinib | Placebo + Gemcitabine + Erlotinib |
|---|---|---|
| Arm/Group Description | Cycle 1 (8-week cycle): Participants received bevacizumab 5 milligrams per kilogram (mg/kg) intravenously (IV) on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg per square meter (mg/m^2) IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, orally (PO), once daily (QD) for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. | Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. |
| Period Title: Overall Study | ||
| STARTED | 306 | 301 |
| COMPLETED | 221 | 233 |
| NOT COMPLETED | 85 | 68 |
Baseline Characteristics
| Arm/Group Title | Bevacizumab + Gemcitabine + Erlotinib | Placebo + Gemcitabine + Erlotinib | Total |
|---|---|---|---|
| Arm/Group Description | Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. | Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. | Total of all reporting groups |
| Overall Participants | 306 | 301 | 607 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
61.5
(10.36)
|
61.0
(10.03)
|
61.2
(10.19)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
132
43.1%
|
113
37.5%
|
245
40.4%
|
| Male |
174
56.9%
|
188
62.5%
|
362
59.6%
|
Outcome Measures
| Title | Duration of Overall Survival - Percentage of Participants With an Event |
|---|---|
| Description | Duration of overall survival (OS) was defined as the time between date of randomization and date of death due to any cause. Participants without an event were censored at the date last known to be alive. Participants who were randomized but not exposed to study drug and had no further follow up were censored at the date of randomization. |
| Time Frame | Randomization, Weeks 1-8 of Cycle 1, Weeks 1-3 of consecutive cycles, 28 days and 3 months after lst treatment, and every 3 months for up to 18 months from last participant randomized |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. |
| Arm/Group Title | Bevacizumab + Gemcitabine + Erlotinib | Placebo + Gemcitabine + Erlotinib |
|---|---|---|
| Arm/Group Description | Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. | Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. |
| Measure Participants | 306 | 301 |
| Number [percentage of participants] |
72.2
23.6%
|
77.4
25.7%
|
| Title | Clinical Benefit Response (CBR) |
|---|---|
| Description | |
| Time Frame | Randomization, Weeks 1-8 of Cycle 1, Weeks 1-3 of consecutive cycles, 28 days and 3 months after lst treatment, and every 3 months for up to 18 months from last participant randomized |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis of the CBR was dependent on the calculation of analgesic therapy (AT); this calculation relies on established conversion factors for different morphine derivatives (MD). Many MD utilized by participants do not have well-established conversion factors, yielding uninterpretable results. Therefore, CBR was not analyzed in this study. |
| Arm/Group Title | Bevacizumab + Gemcitabine + Erlotinib | Placebo + Gemcitabine + Erlotinib |
|---|---|---|
| Arm/Group Description | Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. | Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. |
| Measure Participants | 0 | 0 |
| Title | Progression-Free Survival (PFS) - Percentage of Participants With an Event |
|---|---|
| Description | PFS was defined as the time between the date of randomization and the date of documented progressive disease (PD) defined according to modified Response Evaluation Criteria in Solid Tumors (RECIST) evaluation, or date of death due to any cause. PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum (LD) recorded since the treatment started. Participants without an event were censored at the date of last follow up for progression, or date of last available tumor assessment if no further follow up assessment for progression was performed. Participants who were randomized but not exposed to study drug and had no further follow up were censored at the date of randomization. |
| Time Frame | Screening, Weeks 8, 16, 24, 32, 40, and every 12 weeks thereafter or until confirmed evidence of disease progression |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population. |
| Arm/Group Title | Bevacizumab + Gemcitabine + Erlotinib | Placebo + Gemcitabine + Erlotinib |
|---|---|---|
| Arm/Group Description | Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. | Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. |
| Measure Participants | 306 | 301 |
| Number [percentage of participants] |
84.0
27.5%
|
92.4
30.7%
|
| Title | Progression-Free Survival (PFS) - Time to Event |
|---|---|
| Description | PFS was defined as the time between the date of randomization and the date of documented PD (per RECIST), or date of death due to any cause. Data for participants without an event were censored at the date of last follow up for progression, or date of last available tumor assessment if no further follow up assessment for progression was performed. Participants who were randomized but not exposed to study drug and had no further follow up were censored at the date of randomization. Median PFS was estimated using the Kaplan-Meier method. |
| Time Frame | Screening, Weeks 8, 16, 24, 32, 40, and every 12 weeks thereafter or until confirmed evidence of disease progression |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population |
| Arm/Group Title | Bevacizumab + Gemcitabine + Erlotinib | Placebo + Gemcitabine + Erlotinib |
|---|---|---|
| Arm/Group Description | Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. | Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. |
| Measure Participants | 306 | 301 |
| Median (95% Confidence Interval) [months] |
4.6
|
3.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bevacizumab + Gemcitabine + Erlotinib, Placebo + Gemcitabine + Erlotinib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.73 | |
| Confidence Interval |
(2-Sided) 95% 0.61 to 0.86 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Complete Response (CR), Partial Response (PR), or Stable Disease (SD) at First Postbaseline Tumor Assessment |
|---|---|
| Description | Percentage of participants with CR, PR, or SD according to modified RECIST evaluation at the first postbaseline tumor assessment. CR equaled (=) complete disappearance of all target lesions and non-target disease, with normalization of tumor marker level. PR is greater than or equal to (≥) a 30% decrease of the sum of the LD of all target lesions as referenced to the baseline sum LD of all target lesions. Persistence of one or more non-target lesions(s) and/or maintenance of tumor marker level above normal limits. SD=neither sufficient shrinkage of target lesions to qualify for PR nor sufficient increase to qualify for PD with persistence of one or more non-target lesions(s) and/or maintenance of tumor marker level above normal limits. |
| Time Frame | Baseline and Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. |
| Arm/Group Title | Bevacizumab + Gemcitabine + Erlotinib | Placebo + Gemcitabine + Erlotinib |
|---|---|---|
| Arm/Group Description | Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. | Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. |
| Measure Participants | 306 | 301 |
| Number (95% Confidence Interval) [percentage of participants] |
62.1
20.3%
|
58.5
19.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bevacizumab + Gemcitabine + Erlotinib, Placebo + Gemcitabine + Erlotinib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3621 |
| Comments | ||
| Method | Chi-squared | |
| Comments | Approximate 95% confidence interval (CI) for difference of two rates using Hauck-Anderson method. | |
| Method of Estimation | Estimation Parameter | Difference in Response Rates |
| Estimated Value | 3.62 | |
| Confidence Interval |
(2-Sided) 95% -4.3 to 11.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Duration of Overall Survival - Time to Event |
|---|---|
| Description | Duration of OS was defined as the time between date of randomization and date of death due to any cause. Participants without an event were censored at the date last known to be alive. Participants who were randomized but not exposed to study drug and had no further follow up were censored at the date of randomization. Median duration of survival was estimated using the Kaplan-Meier method. |
| Time Frame | Randomization, Weeks 1-8 of Cycle 1, Weeks 1-3 of consecutive cycles, 28 days and 3 months after lst treatment, and every 3 months for up to 18 months from last participant randomized |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. |
| Arm/Group Title | Bevacizumab + Gemcitabine + Erlotinib | Placebo + Gemcitabine + Erlotinib |
|---|---|---|
| Arm/Group Description | Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. | Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. |
| Measure Participants | 306 | 301 |
| Median (95% Confidence Interval) [months] |
7.1
|
6.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Bevacizumab + Gemcitabine + Erlotinib, Placebo + Gemcitabine + Erlotinib |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2087 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.89 | |
| Confidence Interval |
() 95% 0.74 to 1.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Bevacizumab Concentration in the Presence of Gemcitabine and Erlotinib |
|---|---|
| Description | Blood samples were collected from a subgroup of participants, in selected centers for the determination of bevacizumab serum concentration before the first bevacizumab/placebo exposure (Week 1) and at Weeks 3, 5, 7, and 9. Each time blood samples were collected just (preferably within 1 hour) before the start of the study treatment. |
| Time Frame | Weeks 1, 3, 5, 7, and 9 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. Number (n) = number of participants assessed at a specific visit. |
| Arm/Group Title | Bevacizumab + Gemcitabine + Erlotinib |
|---|---|
| Arm/Group Description | Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. |
| Measure Participants | 78 |
| Week 1 (n=4) |
0.52
(14.98)
|
| Week 3 (n=78) |
27.09
(18.23)
|
| Week 5 (n=73) |
35.23
(24.88)
|
| Week 7 (n=72) |
41.19
(19.68)
|
| Week 9 (n=61) |
44.60
(22.57)
|
Adverse Events
| Time Frame | Adverse Events (AEs) were reported from Day 1 (or prior to Day 1 for serious AEs [SAEs] related to study specific procedures) until 28 days after last dose. Related nonserious SAEs occurring up to 6 months after last dose of study drug were reported. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Related SAEs: reported indefinitely; related AEs: followed to return to baseline/stabilizing or causal relationship changed. Unrelated, mild/moderate AEs: followed for 28 days after last dose. Severe, life-threatening/related AEs: followed to resolution, causal relationship changed or death. | |||
| Arm/Group Title | Bevacizumab + Gemcitabine + Erlotinib | Placebo + Gemcitabine + Erlotinib | ||
| Arm/Group Description | Cycle 1 (8-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received bevacizumab 5 mg/kg IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. | Cycle 1 (8-week cycle): Participants received placebo IV on Days 1, 15, 29, and 43 (followed by 1 week off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, 15, 22, 29, 36, and 43 (followed by 1 week off); and erlotinib 100 mg tablets/capsules, PO, QD for 8 weeks. Cycles 2 and beyond (4-week cycle): Participants received placebo IV on Days 1 and 15 (followed by 2 weeks off); gemcitabine 1000 mg/m^2 IV on Days 1, 8, and 15 (followed by 1 week off); and erlotinib 100 mg tablets/capsules PO QD. Participants continued on treatment until disease progression, unacceptable toxicity, or participant withdrawal. | ||
All Cause Mortality |
||||
| Bevacizumab + Gemcitabine + Erlotinib | Placebo + Gemcitabine + Erlotinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Bevacizumab + Gemcitabine + Erlotinib | Placebo + Gemcitabine + Erlotinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 139/297 (46.8%) | 119/286 (41.6%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 5/297 (1.7%) | 3/286 (1%) | ||
| Febrile neutropenia | 1/297 (0.3%) | 2/286 (0.7%) | ||
| Haemolytic uraemic syndrome | 2/297 (0.7%) | 1/286 (0.3%) | ||
| Neutropenia | 2/297 (0.7%) | 0/286 (0%) | ||
| Thrombocytopenia | 1/297 (0.3%) | 1/286 (0.3%) | ||
| Acquired haemophilia with anti FVIII, XI, or XIII | 1/297 (0.3%) | 0/286 (0%) | ||
| Hypercoagulation | 0/297 (0%) | 1/286 (0.3%) | ||
| Pancytopenia | 1/297 (0.3%) | 0/286 (0%) | ||
| Splenic infarction | 0/297 (0%) | 1/286 (0.3%) | ||
| Cardiac disorders | ||||
| Myocardial infarction | 4/297 (1.3%) | 1/286 (0.3%) | ||
| Cardiac failure | 1/297 (0.3%) | 1/286 (0.3%) | ||
| Acute coronary syndrome | 1/297 (0.3%) | 0/286 (0%) | ||
| Angina pectoris | 1/297 (0.3%) | 0/286 (0%) | ||
| Left ventricular failure | 0/297 (0%) | 1/286 (0.3%) | ||
| Myocardial ischaemia | 1/297 (0.3%) | 0/286 (0%) | ||
| Pericarditis | 0/297 (0%) | 1/286 (0.3%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 5/297 (1.7%) | 2/286 (0.7%) | ||
| Gastrointestinal haemorrhage | 3/297 (1%) | 4/286 (1.4%) | ||
| Nausea | 3/297 (1%) | 4/286 (1.4%) | ||
| Diarrhoea | 2/297 (0.7%) | 4/286 (1.4%) | ||
| Intestinal obstruction | 3/297 (1%) | 3/286 (1%) | ||
| Upper gastrointestinal haemorrhage | 4/297 (1.3%) | 2/286 (0.7%) | ||
| Rectal haemorrhage | 1/297 (0.3%) | 2/286 (0.7%) | ||
| Abdominal pain upper | 1/297 (0.3%) | 1/286 (0.3%) | ||
| Constipation | 1/297 (0.3%) | 1/286 (0.3%) | ||
| Gastric haemorrhage | 2/297 (0.7%) | 0/286 (0%) | ||
| Gastrointestinal perforation | 1/297 (0.3%) | 1/286 (0.3%) | ||
| Gastrointestinal ulcer haemorrhage | 2/297 (0.7%) | 0/286 (0%) | ||
| Haematemesis | 2/297 (0.7%) | 0/286 (0%) | ||
| Ileus | 1/297 (0.3%) | 1/286 (0.3%) | ||
| Ileus paralytic | 2/297 (0.7%) | 0/286 (0%) | ||
| Peritonitis | 2/297 (0.7%) | 0/286 (0%) | ||
| Small intestinal haemorrhage | 0/297 (0%) | 2/286 (0.7%) | ||
| Anal fistula | 1/297 (0.3%) | 0/286 (0%) | ||
| Anal ulcer | 1/297 (0.3%) | 0/286 (0%) | ||
| Ascites | 0/297 (0%) | 1/286 (0.3%) | ||
| Duodenal perforation | 1/297 (0.3%) | 0/286 (0%) | ||
| Duodenal ulcer haemorrhage | 0/297 (0%) | 1/286 (0.3%) | ||
| Dysphagia | 0/297 (0%) | 1/286 (0.3%) | ||
| Faeces discoloured | 0/297 (0%) | 1/286 (0.3%) | ||
| Gastric perforation | 0/297 (0%) | 1/286 (0.3%) | ||
| Gastric ulcer haemorrhage | 0/297 (0%) | 1/286 (0.3%) | ||
| Gastric ulcer perforation | 0/297 (0%) | 1/286 (0.3%) | ||
| Haematochezia | 0/297 (0%) | 1/286 (0.3%) | ||
| Intestinal mass | 1/297 (0.3%) | 0/286 (0%) | ||
| Melaena | 1/297 (0.3%) | 0/286 (0%) | ||
| Pancreatitis acute | 1/297 (0.3%) | 0/286 (0%) | ||
| Peptic ulcer haemorrhage | 0/297 (0%) | 1/286 (0.3%) | ||
| Peritoneal haemorrhage | 1/297 (0.3%) | 0/286 (0%) | ||
| Sigmoiditis | 1/297 (0.3%) | 0/286 (0%) | ||
| Subileus | 0/297 (0%) | 1/286 (0.3%) | ||
| Vomiting | 8/297 (2.7%) | 4/286 (1.4%) | ||
| Intestinal infarction | 0/297 (0%) | 1/286 (0.3%) | ||
| Intestinal perforation | 1/297 (0.3%) | 0/286 (0%) | ||
| Malabsorption | 0/297 (0%) | 1/286 (0.3%) | ||
| Intra-abdominal haematoma | 1/297 (0.3%) | 0/286 (0%) | ||
| General disorders | ||||
| Pyrexia | 16/297 (5.4%) | 11/286 (3.8%) | ||
| General physical health deterioration | 1/297 (0.3%) | 3/286 (1%) | ||
| Asthenia | 1/297 (0.3%) | 2/286 (0.7%) | ||
| Oedema peripheral | 0/297 (0%) | 2/286 (0.7%) | ||
| Death | 0/297 (0%) | 1/286 (0.3%) | ||
| Oedema | 1/297 (0.3%) | 0/286 (0%) | ||
| Sudden death | 1/297 (0.3%) | 0/286 (0%) | ||
| Fatigue | 1/297 (0.3%) | 0/286 (0%) | ||
| Hepatobiliary disorders | ||||
| Cholangitis | 4/297 (1.3%) | 4/286 (1.4%) | ||
| Hepatic function abnormal | 2/297 (0.7%) | 1/286 (0.3%) | ||
| Jaundice | 3/297 (1%) | 0/286 (0%) | ||
| Biliary dilatation | 1/297 (0.3%) | 0/286 (0%) | ||
| Cholangitis acute | 0/297 (0%) | 1/286 (0.3%) | ||
| Cholestasis | 1/297 (0.3%) | 0/286 (0%) | ||
| Gallbladder perforation | 0/297 (0%) | 1/286 (0.3%) | ||
| Hyperbilirubinaemia | 1/297 (0.3%) | 0/286 (0%) | ||
| Jaundice cholestatic | 1/297 (0.3%) | 0/286 (0%) | ||
| Infections and infestations | ||||
| Sepsis | 8/297 (2.7%) | 6/286 (2.1%) | ||
| Pneumonia | 9/297 (3%) | 2/286 (0.7%) | ||
| Abdominal abscess | 2/297 (0.7%) | 1/286 (0.3%) | ||
| Bronchitis | 0/297 (0%) | 3/286 (1%) | ||
| Septic Shock | 0/297 (0%) | 3/286 (1%) | ||
| Bacterial sepsis | 2/297 (0.7%) | 0/286 (0%) | ||
| Biliary tract infection | 0/297 (0%) | 2/286 (0.7%) | ||
| Escherichia sepsis | 2/297 (0.7%) | 0/286 (0%) | ||
| Lower respiratory tract infection | 0/297 (0%) | 2/286 (0.7%) | ||
| Subcutaneous abscess | 2/297 (0.7%) | 0/286 (0%) | ||
| Abscess | 1/297 (0.3%) | 0/286 (0%) | ||
| Bacterial infection | 1/297 (0.3%) | 0/286 (0%) | ||
| Biliary sepsis | 0/297 (0%) | 1/286 (0.3%) | ||
| Cellulitis | 1/297 (0.3%) | 0/286 (0%) | ||
| Central line infection | 0/297 (0%) | 2/286 (0.7%) | ||
| Disseminated cytomegaloviral infection | 0/297 (0%) | 1/286 (0.3%) | ||
| Diverticulitis | 1/297 (0.3%) | 0/286 (0%) | ||
| Infected insect bite | 0/297 (0%) | 1/286 (0.3%) | ||
| Infection | 1/297 (0.3%) | 0/286 (0%) | ||
| Laryngitis | 1/297 (0.3%) | 0/286 (0%) | ||
| Osteomyelitis | 0/297 (0%) | 1/286 (0.3%) | ||
| Peritonitis bacterial | 0/297 (0%) | 1/286 (0.3%) | ||
| Pilonidal cyst | 1/297 (0.3%) | 0/286 (0%) | ||
| Pneumocystis jiroveci pneumonia | 0/297 (0%) | 1/286 (0.3%) | ||
| Pneumonia klebsiella | 0/297 (0%) | 1/286 (0.3%) | ||
| Renal cyst infection | 0/297 (0%) | 1/286 (0.3%) | ||
| Upper respiratory tract infection | 0/297 (0%) | 1/286 (0.3%) | ||
| Wound infection | 1/297 (0.3%) | 0/286 (0%) | ||
| Perianal abcess | 1/297 (0.3%) | 0/286 (0%) | ||
| Gastroenteritis | 1/297 (0.3%) | 0/286 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Overdose | 1/297 (0.3%) | 1/286 (0.3%) | ||
| Stent occlusion | 1/297 (0.3%) | 1/286 (0.3%) | ||
| Femoral neck fracture | 1/297 (0.3%) | 0/286 (0%) | ||
| Head injury | 0/297 (0%) | 1/286 (0.3%) | ||
| Hepatic haematoma | 0/297 (0%) | 1/286 (0.3%) | ||
| Thoracic vertebral fracture | 1/297 (0.3%) | 0/286 (0%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 1/297 (0.3%) | 0/286 (0%) | ||
| Aspartate aminotransferase increased | 1/297 (0.3%) | 0/286 (0%) | ||
| Blood creatinine increased | 1/297 (0.3%) | 0/286 (0%) | ||
| Blood potassium decreased | 1/297 (0.3%) | 0/286 (0%) | ||
| C-reactive protein increased | 1/297 (0.3%) | 0/286 (0%) | ||
| Haemoglobin decreased | 0/297 (0%) | 1/286 (0.3%) | ||
| Hepatic enzyme increased | 1/297 (0.3%) | 0/286 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 3/297 (1%) | 3/286 (1%) | ||
| Anorexia | 0/297 (0%) | 3/286 (1%) | ||
| Hyperglycaemia | 2/297 (0.7%) | 1/286 (0.3%) | ||
| Diabetes mellitus | 0/297 (0%) | 2/286 (0.7%) | ||
| Diabetes mellitus inadequate control | 2/297 (0.7%) | 0/286 (0%) | ||
| Cachexia | 1/297 (0.3%) | 0/286 (0%) | ||
| Type 1 diabetes mellitus | 0/297 (0%) | 1/286 (0.3%) | ||
| Failure to thrive | 1/297 (0.3%) | 0/286 (0%) | ||
| Hyperkalaemia | 1/297 (0.3%) | 0/286 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Pain in extremity | 1/297 (0.3%) | 0/286 (0%) | ||
| Hypercreatinaemia | 1/297 (0.3%) | 0/286 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Endometrial cancer | 1/297 (0.3%) | 0/286 (0%) | ||
| Lymphangiosis carcinomatosa | 0/297 (0%) | 1/286 (0.3%) | ||
| Tumour haemorrhage | 1/297 (0.3%) | 0/286 (0%) | ||
| Nervous system disorders | ||||
| Cerebrovascular accident | 2/297 (0.7%) | 3/286 (1%) | ||
| Cerebral infarction | 1/297 (0.3%) | 1/286 (0.3%) | ||
| Syncope | 1/297 (0.3%) | 1/286 (0.3%) | ||
| Cerebral artery embolism | 1/297 (0.3%) | 0/286 (0%) | ||
| Dizziness | 0/297 (0%) | 1/286 (0.3%) | ||
| Ischaemic stroke | 0/297 (0%) | 1/286 (0.3%) | ||
| Lacunar infarction | 0/297 (0%) | 1/286 (0.3%) | ||
| Neurological symptom | 0/297 (0%) | 1/286 (0.3%) | ||
| Transient ischaemic attack | 0/297 (0%) | 1/286 (0.3%) | ||
| Psychiatric disorders | ||||
| Anxiety | 0/297 (0%) | 1/286 (0.3%) | ||
| Depression | 1/297 (0.3%) | 0/286 (0%) | ||
| Renal and urinary disorders | ||||
| Renal failure | 2/297 (0.7%) | 0/286 (0%) | ||
| Renal impairment | 2/297 (0.7%) | 0/286 (0%) | ||
| Anuria | 0/297 (0%) | 1/286 (0.3%) | ||
| Nephrolithiasis | 0/297 (0%) | 1/286 (0.3%) | ||
| Proteinuria | 1/297 (0.3%) | 0/286 (0%) | ||
| Renal colic | 2/297 (0.7%) | 0/286 (0%) | ||
| Renal failure acute | 0/297 (0%) | 1/286 (0.3%) | ||
| Reproductive system and breast disorders | ||||
| Oedema genital | 1/297 (0.3%) | 0/286 (0%) | ||
| Vaginal haemorrhage | 1/297 (0.3%) | 0/286 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pulmonary embolism | 9/297 (3%) | 12/286 (4.2%) | ||
| Dyspnoea | 3/297 (1%) | 3/286 (1%) | ||
| Respiratory failure | 2/297 (0.7%) | 2/286 (0.7%) | ||
| Interstitial lung disease | 2/297 (0.7%) | 1/286 (0.3%) | ||
| Acute respiratory distress syndrome | 1/297 (0.3%) | 1/286 (0.3%) | ||
| Epistaxis | 2/297 (0.7%) | 0/286 (0%) | ||
| Pleural effusion | 1/297 (0.3%) | 2/286 (0.7%) | ||
| Alveolitis | 1/297 (0.3%) | 0/286 (0%) | ||
| Chronic obstructive pulmonary disease | 0/297 (0%) | 1/286 (0.3%) | ||
| Lung disorder | 0/297 (0%) | 1/286 (0.3%) | ||
| Pneumonitis | 0/297 (0%) | 1/286 (0.3%) | ||
| Pneumothorax | 1/297 (0.3%) | 0/286 (0%) | ||
| Pulmonary Haemorrhage | 1/297 (0.3%) | 0/286 (0%) | ||
| Pulmonary oedema | 0/297 (0%) | 1/286 (0.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 2/297 (0.7%) | 0/286 (0%) | ||
| Blister | 1/297 (0.3%) | 0/286 (0%) | ||
| Eczema | 0/297 (0%) | 1/286 (0.3%) | ||
| Surgical and medical procedures | ||||
| Ileectomy | 1/297 (0.3%) | 0/286 (0%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 4/297 (1.3%) | 5/286 (1.7%) | ||
| Thrombosis | 1/297 (0.3%) | 2/286 (0.7%) | ||
| Aortic dissection | 0/297 (0%) | 1/286 (0.3%) | ||
| Cardiovascular insufficiency | 0/297 (0%) | 1/286 (0.3%) | ||
| Haemorrhage | 1/297 (0.3%) | 0/286 (0%) | ||
| Hypertension | 2/297 (0.7%) | 0/286 (0%) | ||
| Jugular vein thrombosis | 0/297 (0%) | 1/286 (0.3%) | ||
| Subclavian vein thrombosis | 1/297 (0.3%) | 0/286 (0%) | ||
| Vena cava thrombosis | 1/297 (0.3%) | 0/286 (0%) | ||
| Venous thrombosis | 1/297 (0.3%) | 0/286 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Bevacizumab + Gemcitabine + Erlotinib | Placebo + Gemcitabine + Erlotinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 290/297 (97.6%) | 276/286 (96.5%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 77/297 (25.9%) | 96/286 (33.6%) | ||
| Thrombocytopenia | 93/297 (31.3%) | 76/286 (26.6%) | ||
| Neutropenia | 87/297 (29.3%) | 75/286 (26.2%) | ||
| Leukopenia | 16/297 (5.4%) | 20/286 (7%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 145/297 (48.8%) | 144/286 (50.3%) | ||
| Nausea | 135/297 (45.5%) | 146/286 (51%) | ||
| Vomiting | 108/297 (36.4%) | 118/286 (41.3%) | ||
| Constipation | 79/297 (26.6%) | 65/286 (22.7%) | ||
| Abdominal pain | 46/297 (15.5%) | 39/286 (13.6%) | ||
| Abdominal pain upper | 33/297 (11.1%) | 29/286 (10.1%) | ||
| Stomatitis | 34/297 (11.4%) | 19/286 (6.6%) | ||
| Dyspepsia | 25/297 (8.4%) | 20/286 (7%) | ||
| Flatulence | 19/297 (6.4%) | 10/286 (3.5%) | ||
| General disorders | ||||
| Fatigue | 104/297 (35%) | 97/286 (33.9%) | ||
| Pyrexia | 94/297 (31.6%) | 99/286 (34.6%) | ||
| Oedema peripheral | 51/297 (17.2%) | 49/286 (17.1%) | ||
| Asthenia | 41/297 (13.8%) | 44/286 (15.4%) | ||
| Mucosal inflammation | 25/297 (8.4%) | 29/286 (10.1%) | ||
| Chills | 18/297 (6.1%) | 15/286 (5.2%) | ||
| Infections and infestations | ||||
| Urinary tract infection | 29/297 (9.8%) | 17/286 (5.9%) | ||
| Investigations | ||||
| Weight decreased | 15/297 (5.1%) | 21/286 (7.3%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 64/297 (21.5%) | 66/286 (23.1%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 21/297 (7.1%) | 22/286 (7.7%) | ||
| Pain in extremity | 20/297 (6.7%) | 9/286 (3.1%) | ||
| Nervous system disorders | ||||
| Headache | 39/297 (13.1%) | 24/286 (8.4%) | ||
| Dysgeusia | 35/297 (11.8%) | 26/286 (9.1%) | ||
| Dizziness | 20/297 (6.7%) | 23/286 (8%) | ||
| Psychiatric disorders | ||||
| Insomnia | 35/297 (11.8%) | 25/286 (8.7%) | ||
| Depression | 15/297 (5.1%) | 18/286 (6.3%) | ||
| Anxiety | 18/297 (6.1%) | 10/286 (3.5%) | ||
| Renal and urinary disorders | ||||
| Proteinuria | 15/297 (5.1%) | 4/286 (1.4%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Epistaxis | 89/297 (30%) | 32/286 (11.2%) | ||
| Dyspnoea | 31/297 (10.4%) | 26/286 (9.1%) | ||
| Cough | 24/297 (8.1%) | 24/286 (8.4%) | ||
| Pharyngolaryngeal pain | 16/297 (5.4%) | 7/286 (2.4%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 146/297 (49.2%) | 126/286 (44.1%) | ||
| Alopecia | 40/297 (13.5%) | 44/286 (15.4%) | ||
| Dry skin | 37/297 (12.5%) | 23/286 (8%) | ||
| Acne | 30/297 (10.1%) | 17/286 (5.9%) | ||
| Dermatitis acneiform | 25/297 (8.4%) | 19/286 (6.6%) | ||
| Pruritus | 22/297 (7.4%) | 18/286 (6.3%) | ||
| Vascular disorders | ||||
| Hypertension | 58/297 (19.5%) | 28/286 (9.8%) | ||
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 that 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:
NCT01214720
Other Study ID Numbers:
- BO17706
First Posted:
Oct 5, 2010
Last Update Posted:
Aug 13, 2014
Last Verified:
Jul 1, 2014