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A Study of Avastin (Bevacizumab) in Combination With Carboplatin-Based Chemotherapy in Patients With Advanced or Recurrent Non-Squamous Non-Small Cell Lung Cancer.

Primary Purpose

Non-Small Cell Lung Cancer

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
bevacizumab [Avastin]
bevacizumab [Avastin]
Carboplatin-based chemotherapy
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • adult patients, >=18 years of age;
  • locally advanced metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC);
  • >=1 measurable tumor lesion;
  • ECOG performance status 0-1.

Exclusion Criteria:

  • prior chemotherapy or treatment with another systemic anti-cancer agent;
  • evidence of CNS metastases;
  • history of grade 2 or higher hemoptysis;
  • evidence of tumor invading or abutting major blood vessels;
  • malignancies other than NSCLC within 5 years prior to randomization, other than adequately treated cancer in situ of cervix, basal or squamous cell skin cancer, localized prostate cancer or DCIS;
  • clinically significant cardiovascular disease;
  • current or recent use of aspirin (>325mg/day) or full dose anticoagulants or thrombolytic agents for therapeutic purposes.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

1

2

Arm Description

Outcomes

Primary Outcome Measures

Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level
Overall response was analyzed and correlated within dichotomized (low- and high-level) baseline plasma biomarker (basic fibroblast growth factor [bFGF], E-selection, intracellular adhesion molecule [ICAM], placental growth factor [PlGF], vascular endothelial growth factor A [VEGF A], vascular endothelial growth factor receptor [VEGFR]-1, and VEGFR-2) subgroups: low-level equals (=) less than or equal to (≤) median baseline level, high-level=greater than (>) median baseline level. Per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.0 CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR defined as greater than or equal to (≥)30 percent (%) decrease under baseline of the sum of the longest diameter (LD) of all target lesions. No unequivocal progression of non-target disease; no new lesions. Complete and partial responses must have been confirmed no less than 4 weeks after criteria for response were first met

Secondary Outcome Measures

Progression-Free Survival - Percentage of Participants With an Event
PFS was defined as the time between randomization and progressive disease (PD) according to RECIST criteria, or death due to any cause. PD was defined as 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. Disease progression was evaluated according to the RECIST using computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, X-ray, bone scans, or clinical examination. Participants without an event were censored at the date of last follow up for progression. Participants with no post baseline follow-up for progression were censored at the day of randomization.
Progression-Free Survival - Time to Event
PFS was defined as the time between randomization and disease progression or death due to any cause. Participants without an event were censored at the date of last follow up for progression. Participants with no post baseline follow-up for progression were censored at the day of randomization. Disease progression was evaluated according to the RECIST using CT scans, MRI scans, X-ray, bone scans, or clinical examination. Median PFS was estimated using the Kaplan-Meier method.
Percentage of Participants With Objective Response
Percentage of participants with CR or PR according to RECIST criteria. Per RECIST v1.0: CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as ≥30% decrease under baseline of the sum of the LD of all target lesions. No unequivocal progression of non-target disease. No new lesions. Complete and partial responses were confirmed no less than 4 weeks after the criteria for response were first met.
Percentage of Participants With Measurable Disease at Baseline Who Achieved CR, PR, or Stable Disease (SD) for at Least 6 Weeks
Percentage of participants with measurable disease at baseline who on assessment achieved CR, PR, or SD according to RECIST. Per RECIST v1.0: CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as ≥30% decrease under baseline of the sum of the LD of all target lesions. No unequivocal progression of non-target disease. No new lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since start of treatment. Complete and partial responses must have been confirmed no less than 4 weeks after the criteria for response were first met. For participants with SD, follow-up assessments must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks.
Duration of Response - Percentage of Participants With an Event
Duration of response is defined as time in months from the first documentation of objective tumor response (CR or PR) to objective tumor progression or death due to any cause. Participants without an event (documented progression or death) were censored at the date of last follow-up for progression. Duration of response was only calculated for participants who had a confirmed objective tumor response (CR or PR).
Duration of Response - Time to Event
The median time, in months, from the first documentation of objective tumor response (CR or PR) to objective tumor progression or death due to any cause. Participants without an event (documented progression or death) were censored at the date of last follow-up for progression. Duration of response was only calculated for participants who had a confirmed objective tumor response (CR or PR). Median Duration of Response was estimated using the Kaplan-Meier method.
Overall Survival - Percentage of Participants With an Event
Overall survival was defined as the time between randomization and death due to any cause. Participants without an event were censored at the last time they were known to be alive. Overall Survival was estimated using the Kaplan-Meier method.
Overall Survival - Time to Event
Overall survival was defined as the time between randomization and death due to any cause. Participants without an event were censored at the last time they were known to be alive. Overall Survival was estimated using the Kaplan-Meier method.

Full Information

First Posted
June 17, 2008
Last Updated
September 23, 2014
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT00700180
Brief Title
A Study of Avastin (Bevacizumab) in Combination With Carboplatin-Based Chemotherapy in Patients With Advanced or Recurrent Non-Squamous Non-Small Cell Lung Cancer.
Official Title
A Randomized, Open-label Study to Explore the Correlation of Biomarkers With Response Rate in Chemo-naive Patients With Advanced or Recurrent Non-squamous Non-small Cell Lung Cancer Who Receive Treatment With Avastin in Addition to Carboplatin-based Chemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
September 2008 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
September 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary
This study will explore the correlation of biomarkers with response rate, and the overall efficacy and safety, of Avastin in combination with carboplatin-based chemotherapy in patients with advanced or recurrent non-squamous non-small cell lung cancer. Patients will be randomized to one of 2 groups, to receive either Avastin 7.5mg/kg iv on day 1 of each 3 week cycle, or Avastin 15mg/kg iv on day 1 of each 3 week cycle; all patients will also receive treatment with carboplatin and either gemcitabine or paclitaxel for a maximum of 6 cycles. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
303 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Title
2
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
bevacizumab [Avastin]
Intervention Description
7.5mg/kg iv on day 1 of each 3 week cycle
Intervention Type
Drug
Intervention Name(s)
bevacizumab [Avastin]
Intervention Description
15mg/kg iv on day 1 of each 3 week cycle
Intervention Type
Drug
Intervention Name(s)
Carboplatin-based chemotherapy
Intervention Description
As prescribed
Primary Outcome Measure Information:
Title
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level
Description
Overall response was analyzed and correlated within dichotomized (low- and high-level) baseline plasma biomarker (basic fibroblast growth factor [bFGF], E-selection, intracellular adhesion molecule [ICAM], placental growth factor [PlGF], vascular endothelial growth factor A [VEGF A], vascular endothelial growth factor receptor [VEGFR]-1, and VEGFR-2) subgroups: low-level equals (=) less than or equal to (≤) median baseline level, high-level=greater than (>) median baseline level. Per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.0 CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR defined as greater than or equal to (≥)30 percent (%) decrease under baseline of the sum of the longest diameter (LD) of all target lesions. No unequivocal progression of non-target disease; no new lesions. Complete and partial responses must have been confirmed no less than 4 weeks after criteria for response were first met
Time Frame
Baseline, Day 21 of Cycles 2, 4, and 6 (Bv + chemo), Day 21 of Cycles 7, 8, 9, and 10 (Bv), Day 21 of every other cycle (Bv), and at disease progression.
Secondary Outcome Measure Information:
Title
Progression-Free Survival - Percentage of Participants With an Event
Description
PFS was defined as the time between randomization and progressive disease (PD) according to RECIST criteria, or death due to any cause. PD was defined as 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. Disease progression was evaluated according to the RECIST using computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, X-ray, bone scans, or clinical examination. Participants without an event were censored at the date of last follow up for progression. Participants with no post baseline follow-up for progression were censored at the day of randomization.
Time Frame
Baseline, Day 1, weekly to disease progression
Title
Progression-Free Survival - Time to Event
Description
PFS was defined as the time between randomization and disease progression or death due to any cause. Participants without an event were censored at the date of last follow up for progression. Participants with no post baseline follow-up for progression were censored at the day of randomization. Disease progression was evaluated according to the RECIST using CT scans, MRI scans, X-ray, bone scans, or clinical examination. Median PFS was estimated using the Kaplan-Meier method.
Time Frame
Baseline, Day 1, weekly to disease progression
Title
Percentage of Participants With Objective Response
Description
Percentage of participants with CR or PR according to RECIST criteria. Per RECIST v1.0: CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as ≥30% decrease under baseline of the sum of the LD of all target lesions. No unequivocal progression of non-target disease. No new lesions. Complete and partial responses were confirmed no less than 4 weeks after the criteria for response were first met.
Time Frame
Baseline, Day 21 of Cycles 2, 4, and 6, Day 21 of Cycles 7, 8, 9, and 10, Day 21 of every other cycle, and at disease progression
Title
Percentage of Participants With Measurable Disease at Baseline Who Achieved CR, PR, or Stable Disease (SD) for at Least 6 Weeks
Description
Percentage of participants with measurable disease at baseline who on assessment achieved CR, PR, or SD according to RECIST. Per RECIST v1.0: CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as ≥30% decrease under baseline of the sum of the LD of all target lesions. No unequivocal progression of non-target disease. No new lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since start of treatment. Complete and partial responses must have been confirmed no less than 4 weeks after the criteria for response were first met. For participants with SD, follow-up assessments must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks.
Time Frame
Baseline, Day 21 of Cycles 2, 4, and 6, Day 21 of Cycles 7, 8, 9, and 10, Day 21 of every other cycle, and at disease progression
Title
Duration of Response - Percentage of Participants With an Event
Description
Duration of response is defined as time in months from the first documentation of objective tumor response (CR or PR) to objective tumor progression or death due to any cause. Participants without an event (documented progression or death) were censored at the date of last follow-up for progression. Duration of response was only calculated for participants who had a confirmed objective tumor response (CR or PR).
Time Frame
Baseline, Day 21 of Cycles 2, 4, and 6, Day 21 of Cycles 7, 8, 9, and 10, Day 21 of every other cycle, and at disease progression
Title
Duration of Response - Time to Event
Description
The median time, in months, from the first documentation of objective tumor response (CR or PR) to objective tumor progression or death due to any cause. Participants without an event (documented progression or death) were censored at the date of last follow-up for progression. Duration of response was only calculated for participants who had a confirmed objective tumor response (CR or PR). Median Duration of Response was estimated using the Kaplan-Meier method.
Time Frame
Baseline, Day 21 of Cycles 2, 4, and 6 (Bv + chemo), Day 21 of Cycles 7, 8, 9, and 10 (Bv), Day 21 of every other cycle (Bv), and at disease progression.
Title
Overall Survival - Percentage of Participants With an Event
Description
Overall survival was defined as the time between randomization and death due to any cause. Participants without an event were censored at the last time they were known to be alive. Overall Survival was estimated using the Kaplan-Meier method.
Time Frame
Baseline, weekly to 28 days after last dose of study treatment, every 8 weeks thereafter to death due to any cause
Title
Overall Survival - Time to Event
Description
Overall survival was defined as the time between randomization and death due to any cause. Participants without an event were censored at the last time they were known to be alive. Overall Survival was estimated using the Kaplan-Meier method.
Time Frame
Baseline, weekly to death due to any cause, or to end of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: adult patients, >=18 years of age; locally advanced metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC); >=1 measurable tumor lesion; ECOG performance status 0-1. Exclusion Criteria: prior chemotherapy or treatment with another systemic anti-cancer agent; evidence of CNS metastases; history of grade 2 or higher hemoptysis; evidence of tumor invading or abutting major blood vessels; malignancies other than NSCLC within 5 years prior to randomization, other than adequately treated cancer in situ of cervix, basal or squamous cell skin cancer, localized prostate cancer or DCIS; clinically significant cardiovascular disease; current or recent use of aspirin (>325mg/day) or full dose anticoagulants or thrombolytic agents for therapeutic purposes.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
St. Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5041
Country
Australia
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5065
Country
Australia
City
Box Hill
State/Province
Victoria
ZIP/Postal Code
3128
Country
Australia
City
Fitzroy
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
City
Antwerpen
ZIP/Postal Code
2020
Country
Belgium
City
Liege
ZIP/Postal Code
4000
Country
Belgium
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G2M9
Country
Canada
City
Ostrava
ZIP/Postal Code
708 52
Country
Czech Republic
City
Praha
ZIP/Postal Code
180 01
Country
Czech Republic
City
Odense
ZIP/Postal Code
5000
Country
Denmark
City
Paris
ZIP/Postal Code
75970
Country
France
City
Rouen
ZIP/Postal Code
76031
Country
France
City
Bad Berka
ZIP/Postal Code
99437
Country
Germany
City
Grosshansdorf
ZIP/Postal Code
22927
Country
Germany
City
Hamburg
ZIP/Postal Code
21075
Country
Germany
City
Oldenburg
ZIP/Postal Code
26121
Country
Germany
City
Hong Kong
ZIP/Postal Code
852
Country
Hong Kong
City
Hong Kong
Country
Hong Kong
City
Budapest
ZIP/Postal Code
1529
Country
Hungary
City
Edeleny
ZIP/Postal Code
3780
Country
Hungary
City
Sopron
ZIP/Postal Code
9400
Country
Hungary
City
Szombathely
ZIP/Postal Code
9700
Country
Hungary
City
Torokbalint
ZIP/Postal Code
2045
Country
Hungary
City
Milano
ZIP/Postal Code
20162
Country
Italy
City
Milan
ZIP/Postal Code
20141
Country
Italy
City
Orbassano
ZIP/Postal Code
10043
Country
Italy
City
Roma
ZIP/Postal Code
00168
Country
Italy
City
Den Haag
ZIP/Postal Code
2504 LN
Country
Netherlands
City
Enschede
ZIP/Postal Code
7500 KA
Country
Netherlands
City
Hoorn
ZIP/Postal Code
1624 NP
Country
Netherlands
City
Nieuwegein
ZIP/Postal Code
3435 CM
Country
Netherlands
City
Rotterdam
ZIP/Postal Code
3075 EA
Country
Netherlands
City
Poznan
ZIP/Postal Code
60-569
Country
Poland
City
Warszawa
ZIP/Postal Code
02-781
Country
Poland
City
Zabrze
ZIP/Postal Code
41-843
Country
Poland
City
Arkhangelsk
ZIP/Postal Code
163045
Country
Russian Federation
City
Chelyabinsk
ZIP/Postal Code
454 087
Country
Russian Federation
City
Kazan
ZIP/Postal Code
420029
Country
Russian Federation
City
Kazan
ZIP/Postal Code
420111
Country
Russian Federation
City
Krasnodar
ZIP/Postal Code
350040
Country
Russian Federation
City
Krasnodar
ZIP/Postal Code
350086
Country
Russian Federation
City
Moscow
ZIP/Postal Code
105229
Country
Russian Federation
City
Moscow
ZIP/Postal Code
115478
Country
Russian Federation
City
Saint-Petersburg
ZIP/Postal Code
197758
Country
Russian Federation
City
St Petersburg
ZIP/Postal Code
197089
Country
Russian Federation
City
Barakaldo
State/Province
Vizcaya
ZIP/Postal Code
48903
Country
Spain
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
City
Valencia
ZIP/Postal Code
46009
Country
Spain
City
Valencia
ZIP/Postal Code
46010
Country
Spain
City
Changhua
ZIP/Postal Code
500
Country
Taiwan
City
Taichung
ZIP/Postal Code
402
Country
Taiwan
City
Taichung
ZIP/Postal Code
404
Country
Taiwan
City
Taichung
ZIP/Postal Code
407
Country
Taiwan
City
Taipei
ZIP/Postal Code
100
Country
Taiwan
City
Aberdeen
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
City
Chelmsford
ZIP/Postal Code
CM1 7ET
Country
United Kingdom
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

A Study of Avastin (Bevacizumab) in Combination With Carboplatin-Based Chemotherapy in Patients With Advanced or Recurrent Non-Squamous Non-Small Cell Lung Cancer.

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