A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab)/Docetaxel in Patients With HER2 Positive Metastatic Breast Cancer.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00391092
First received: October 20, 2006
Last updated: August 21, 2015
Last verified: August 2015

October 20, 2006
August 21, 2015
September 2006
August 2014   (final data collection date for primary outcome measure)
Progression Free Survival (PFS) [ Time Frame: 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) ] [ Designated as safety issue: No ]
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.
Progression-free survival
Complete list of historical versions of study NCT00391092 on ClinicalTrials.gov Archive Site
  • Overall Survival (OS) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.
  • 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 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.
  • Duration of Response (DR) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.
  • Time to Treatment Failure (TTF) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.
  • Functional Assessment of Cancer Therapy - Generic (FACT-G) and Functional Assessment of Cancer Therapy - Breast (FACT-B) Subscale Scores [ Time Frame: 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]) ] [ Designated as safety issue: No ]
    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.
  • Change From Baseline for FACT-G and FACT-B [ Time Frame: 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]) ] [ Designated as safety issue: No ]
    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.
Efficacy: Overall survival, best overall response, duration of response, time to treatment failure, quality of life. Safety: AEs, targeted events including CHF, laboratory parameters.
Not Provided
Not Provided
 
A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab)/Docetaxel in Patients With HER2 Positive Metastatic Breast Cancer.
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.

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
  • Drug: bevacizumab [Avastin]
    15mg/kg iv every 3 weeks
  • Drug: Docetaxel
    100mg/m2 iv every 3 weeks
  • Drug: Herceptin
    8mg/kg iv loading dose, followed by 6mg/kg iv every 3 weeks
  • Experimental: 1
    Interventions:
    • Drug: bevacizumab [Avastin]
    • Drug: Docetaxel
    • Drug: Herceptin
  • Active Comparator: 2
    Interventions:
    • Drug: Docetaxel
    • Drug: Herceptin
Gianni L, Romieu GH, Lichinitser M, Serrano SV, Mansutti M, Pivot X, Mariani P, Andre F, Chan A, Lipatov O, Chan S, Wardley A, Greil R, Moore N, Prot S, Pallaud C, Semiglazov V. AVEREL: a randomized phase III Trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer. J Clin Oncol. 2013 May 10;31(14):1719-25. doi: 10.1200/JCO.2012.44.7912. Epub 2013 Apr 8.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
424
August 2014
August 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • adult patients, >=18 years of age;
  • HER2 positive breast cancer with locally recurrent or metastatic lesions;
  • eligible for chemotherapy;
  • baseline LVEF >=50%.

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).
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Australia,   Austria,   Bosnia and Herzegovina,   Brazil,   Canada,   Czech Republic,   France,   Italy,   Mexico,   Romania,   Russian Federation,   Spain,   Turkey,   United Kingdom,   Uruguay
Belgium,   Germany
 
NCT00391092
BO20231
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP