Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00391092




Trial ID
NCT00391092
Ethics application status
Date submitted
20/10/2006
Date registered
20/10/2006
Date last updated
21/08/2015

Titles & IDs
Public title
A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab)/Docetaxel in Patients With HER2 Positive Metastatic Breast Cancer.
Scientific title
A Randomized, Open-label Study to Compare the Effect of First-line Treatment With Avastin in Combination With Herceptin/Docetaxel and Herceptin/Docetaxel Alone on Progression-free Survival in Patients With HER2 Positive Locally Recurrent or Metastatic Breast Cancer.
Secondary ID [1] 0 0
BO20231
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - bevacizumab [Avastin]
Treatment: Drugs - Docetaxel
Treatment: Drugs - Herceptin

Experimental: 1 -

Active Comparator: 2 -


Treatment: Drugs: bevacizumab [Avastin]
15mg/kg iv every 3 weeks

Treatment: Drugs: Docetaxel
100mg/m2 iv every 3 weeks

Treatment: Drugs: Herceptin
8mg/kg iv loading dose, followed by 6mg/kg iv every 3 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) - PFS was defined as the time from randomization to time of first documented disease progression (unequivocal progression of existing non-target lesions) or death, whichever occurred first as assessed by Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0). Progressive disease is defined using RECIST v1.0 as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started. Primary PFS variable was defined based on the investigators' assessments and the statistical conclusions on the primary efficacy endpoint were based on investigator assessed PFS. PFS was estimated using Kaplan-Meier methods.
Timepoint [1] 0 0
Every 9 weeks up to Week 36, thereafter every 12 weeks until disease progression (up to the clinical cutoff of 30 June 2011, up to 4.75 years)
Secondary outcome [1] 0 0
Overall Survival (OS) - OS was defined as the time from randomization to the date of death, regardless of the cause of death. OS was estimated using Kaplan-Meier methods.
Timepoint [1] 0 0
Every 9 weeks up to Week 36, thereafter every 12 weeks until disease progression (up to the clinical cutoff of 30 June 2011, up to 4.75 years)
Secondary outcome [2] 0 0
Percentage of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR) in Participants With Measurable Disease at Baseline - Best OR was assessed using RECIST v1.0 criteria. Participants were classified as responders if their best OR was either confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of the longest diameter [LD] of target lesions, taking as reference the baseline sum LD). Participants without any post-baseline assessments were regarded as non-responders. The 95% CI for the one sample binomial using Pearson-Clopper method.
Timepoint [2] 0 0
Every 9 weeks up to Week 36, thereafter every 12 weeks until disease progression (up to the clinical cutoff of 30 June 2011, up to 4.75 years)
Secondary outcome [3] 0 0
Duration of Response (DR) - DR was defined as the time when response (CR or PR per RECIST v1.0) was first documented to the date of disease progression per RECIST v1.0 (unequivocal progression of existing non-target lesions) or death. Progressive disease is defined using RECIST v1.0 as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started.
Timepoint [3] 0 0
Every 9 weeks up to Week 36, thereafter every 12 weeks until disease progression (up to the clinical cutoff of 30 June 2011, up to 4.75 years)
Secondary outcome [4] 0 0
Time to Treatment Failure (TTF) - TTF was defined as the time between randomization and date of disease progression (per RECIST v1.0; unequivocal progression of existing non-target lesions), death, or withdrawal of treatment due to adverse events, withdrawal of informed consent, insufficient therapeutic response, refusal of treatment/failure to co-operate, or failure to return, whichever occurred first. Progressive disease is defined using RECIST v1.0 as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started.
Timepoint [4] 0 0
Every 9 weeks up to Week 36, thereafter every 12 weeks until disease progression (up to the clinical cutoff of 30 June 2011, up to 4.75 years)
Secondary outcome [5] 0 0
Functional Assessment of Cancer Therapy - Generic (FACT-G) and Functional Assessment of Cancer Therapy - Breast (FACT-B) Subscale Scores - FACT-G is core questionnaire of Functional Assessment of Chronic Illness Therapy (FACIT) measurement system to evaluate quality of life (QoL) in cancer population. FACT-G consisted of 27 questions grouped in 4 domains of general Health-Related QoL (HRQoL): Physical Well-being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB) and Functional Well-Being (FWB); each ranged from 0 (not at all) to 4 (very much). FACT-G ranged between 0-108. Since questions could be reversed coded, as appropriate, before calculating FACT-G, 0 and 108 could be considered worst and best health states. FACT -B is used for assessment of HRQoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: 7 items for each physical, functional, social/family; all 3 ranged from 0-28, emotional (6 items) ranged from 0-24, and breast cancer subscale (9 items) ranged from 0-36. All single-item measures ranges from 0-144. High scale score represents a better QoL.
Timepoint [5] 0 0
Baseline, Cycles 3, 5, 11, and post progressive disease (PD; 14 to 28 days after disease progression [up to the clinical cutoff of 30 June 2011, up to 4.75 years])
Secondary outcome [6] 0 0
Change From Baseline for FACT-G and FACT-B - FACT-G is core questionnaire of Functional Assessment of Chronic Illness Therapy (FACIT) measurement system to evaluate quality of life (QoL) in cancer population. FACT-G consisted of 27 questions grouped in 4 domains of general Health-Related QoL (HRQoL): Physical Well-being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB) and Functional Well-Being (FWB); each ranged from 0 (not at all) to 4 (very much). FACT-G ranged between 0-108. Since questions could be reversed coded, as appropriate, before calculating FACT-G, 0 and 108 could be considered worst and best health states. FACT -B is used for assessment of HRQoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: 7 items for each physical, functional, social/family; all 3 ranged from 0-28, emotional (6 items) ranged from 0-24, and breast cancer subscale (9 items) ranged from 0-36. All single-item measures ranges from 0-144. High scale score represents a better QoL.
Timepoint [6] 0 0
Baseline, Cycles 3, 5, 11, and post PD (14 to 28 days after disease progression [up to the clinical cutoff of 30 June 2011, up to 4.75 years])

Eligibility
Key inclusion criteria
- adult patients, >=18 years of age;

- HER2 positive breast cancer with locally recurrent or metastatic lesions;

- eligible for chemotherapy;

- baseline LVEF >=50%.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- previous chemotherapy for metastatic or locally recurrent breast cancer;

- previous radiotherapy for metastatic breast cancer (except for metastatic bone pain
relief);

- other primary tumor within last 5 years, with the exception of basal or squamous skin
cancer, or in situ cancer of the cervix;

- clinically significant cardiovascular disease;

- chronic daily treatment with aspirin (>325mg/day) or clopidogrel (>75mg/day).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
- Lismore
Recruitment hospital [2] 0 0
- Newcastle
Recruitment hospital [3] 0 0
- Port Macquarie
Recruitment hospital [4] 0 0
- Wahroonga
Recruitment hospital [5] 0 0
- Wollongong
Recruitment hospital [6] 0 0
- Auchenflower
Recruitment hospital [7] 0 0
- Nambour
Recruitment hospital [8] 0 0
- Fitzroy
Recruitment hospital [9] 0 0
- Geelong
Recruitment hospital [10] 0 0
- Perth
Recruitment postcode(s) [1] 0 0
2480 - Lismore
Recruitment postcode(s) [2] 0 0
2298 - Newcastle
Recruitment postcode(s) [3] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [4] 0 0
2076 - Wahroonga
Recruitment postcode(s) [5] 0 0
2500 - Wollongong
Recruitment postcode(s) [6] 0 0
4066 - Auchenflower
Recruitment postcode(s) [7] 0 0
4560 - Nambour
Recruitment postcode(s) [8] 0 0
3065 - Fitzroy
Recruitment postcode(s) [9] 0 0
3220 - Geelong
Recruitment postcode(s) [10] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Argentina
State/province [2] 0 0
Cordoba
Country [3] 0 0
Argentina
State/province [3] 0 0
La Plata
Country [4] 0 0
Argentina
State/province [4] 0 0
Mar del Plata
Country [5] 0 0
Argentina
State/province [5] 0 0
Mendoza
Country [6] 0 0
Argentina
State/province [6] 0 0
Salta
Country [7] 0 0
Argentina
State/province [7] 0 0
San Martin
Country [8] 0 0
Argentina
State/province [8] 0 0
Santa Fe
Country [9] 0 0
Austria
State/province [9] 0 0
Graz
Country [10] 0 0
Austria
State/province [10] 0 0
Salzburg
Country [11] 0 0
Austria
State/province [11] 0 0
Vöcklabruck
Country [12] 0 0
Austria
State/province [12] 0 0
Wien
Country [13] 0 0
Bosnia and Herzegovina
State/province [13] 0 0
Banja Luka
Country [14] 0 0
Bosnia and Herzegovina
State/province [14] 0 0
Sarajevo
Country [15] 0 0
Bosnia and Herzegovina
State/province [15] 0 0
Tuzla
Country [16] 0 0
Brazil
State/province [16] 0 0
GO
Country [17] 0 0
Brazil
State/province [17] 0 0
RS
Country [18] 0 0
Brazil
State/province [18] 0 0
SC
Country [19] 0 0
Brazil
State/province [19] 0 0
SP
Country [20] 0 0
Canada
State/province [20] 0 0
Alberta
Country [21] 0 0
Canada
State/province [21] 0 0
British Columbia
Country [22] 0 0
Canada
State/province [22] 0 0
Nova Scotia
Country [23] 0 0
Canada
State/province [23] 0 0
Ontario
Country [24] 0 0
Canada
State/province [24] 0 0
Quebec
Country [25] 0 0
Canada
State/province [25] 0 0
Saskatchewan
Country [26] 0 0
Czech Republic
State/province [26] 0 0
Praha 2
Country [27] 0 0
Czech Republic
State/province [27] 0 0
Praha 5
Country [28] 0 0
France
State/province [28] 0 0
Avignon
Country [29] 0 0
France
State/province [29] 0 0
Besancon
Country [30] 0 0
France
State/province [30] 0 0
Bordeaux
Country [31] 0 0
France
State/province [31] 0 0
Caen
Country [32] 0 0
France
State/province [32] 0 0
Clermont Ferrand
Country [33] 0 0
France
State/province [33] 0 0
Dijon
Country [34] 0 0
France
State/province [34] 0 0
Lille
Country [35] 0 0
France
State/province [35] 0 0
Montpellier
Country [36] 0 0
France
State/province [36] 0 0
Villejuif
Country [37] 0 0
Italy
State/province [37] 0 0
Emilia-Romagna
Country [38] 0 0
Italy
State/province [38] 0 0
Friuli-Venezia Giulia
Country [39] 0 0
Italy
State/province [39] 0 0
Lombardia
Country [40] 0 0
Mexico
State/province [40] 0 0
Acapulco
Country [41] 0 0
Mexico
State/province [41] 0 0
Guadalajara
Country [42] 0 0
Mexico
State/province [42] 0 0
Merida
Country [43] 0 0
Mexico
State/province [43] 0 0
Monterrey
Country [44] 0 0
Mexico
State/province [44] 0 0
Torreon
Country [45] 0 0
Romania
State/province [45] 0 0
Bucharest
Country [46] 0 0
Romania
State/province [46] 0 0
Bucuresti
Country [47] 0 0
Romania
State/province [47] 0 0
Cluj Napoca
Country [48] 0 0
Romania
State/province [48] 0 0
Cluj-Napoca
Country [49] 0 0
Romania
State/province [49] 0 0
Iasi
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Kazan
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Moscow
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Obninsk
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Ryazan
Country [54] 0 0
Russian Federation
State/province [54] 0 0
Saint-Petersburg
Country [55] 0 0
Russian Federation
State/province [55] 0 0
UFA
Country [56] 0 0
Spain
State/province [56] 0 0
Barcelona
Country [57] 0 0
Spain
State/province [57] 0 0
Cordoba
Country [58] 0 0
Spain
State/province [58] 0 0
Madrid
Country [59] 0 0
Spain
State/province [59] 0 0
Zaragoza
Country [60] 0 0
Turkey
State/province [60] 0 0
Izmir
Country [61] 0 0
Turkey
State/province [61] 0 0
Sihhiye, ANKARA
Country [62] 0 0
United Kingdom
State/province [62] 0 0
Exeter
Country [63] 0 0
United Kingdom
State/province [63] 0 0
London
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Manchester
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Nottingham
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Preston
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Rhyl
Country [68] 0 0
United Kingdom
State/province [68] 0 0
Stoke-on-Trent
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Weston Super Mare
Country [70] 0 0
Uruguay
State/province [70] 0 0
Montevideo

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This 2 arm study will compare the efficacy and safety of Avastin plus Herceptin/docetaxel,
versus Herceptin/docetaxel alone, in patients with HER2 positive locally recurrent or
metastatic breast cancer who have not received prior chemotherapy for their metastatic
disease. Patients will be randomized 1:1 to receive either Avastin (15mg/kg iv q3weeks) +
Herceptin (8mg/kg iv loading dose and 6mg/kg iv q3weeks maintenance) + docetaxel (100mg/m2 iv
q3weeks) or Herceptin + docetaxel alone. The anticipated time on study treatment is until
disease progression, and the target sample size is 100-500 individuals.
Trial website
https://clinicaltrials.gov/show/NCT00391092
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries