A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab) and Xeloda (Capecitabine) in Patients With HER2-Positive Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00811135
First received: December 16, 2008
Last updated: November 3, 2015
Last verified: November 2015
  Purpose
This single arm study will assess the efficacy and safety of Avastin in combination with Herceptin and Xeloda as first-line treatment of patients with HER2-positive locally recurrent or metastatic breast cancer. Patients will receive 3-weekly treatment cycles of Herceptin (8mg/kg iv on day 1 of first cycle, followed by 6mg/kg iv maintenance dose on day 1 of subsequent cycles), Xeloda (1000mg/m2 bid po on days 1-14 of each treatment cycle) and Avastin (15mg/kg on day 2 of first treatment cycle,and on day 1 of each subsequent cycle).The anticipated time on study treatment is until disease progression, and the target sample size is <100 individuals.

Condition Intervention Phase
Breast Cancer
Drug: bevacizumab [Avastin]
Drug: capecitabine [Xeloda]
Drug: trastuzumab [Herceptin]
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single Arm Open-label, Phase II Study of Bevacizumab in Combination With Trastuzumab and Capecitabine as First-line Treatment of Patients With HER2-positive Locally Recurrent or Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) [ Time Frame: Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) ] [ Designated as safety issue: No ]
    Tumor response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.0. BOR was defined as the best response recorded for a participant from the start of treatment until disease progression/recurrence. Percentage of participants with a BOR of confirmed CR or PR (responders) was reported. CR: disappearance of all target and non-target lesions and normalization of tumor marker level; PR: at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Confirmed responses were those which were confirmed by a repeat assessment, performed 4 weeks after the criteria for response first met.


Secondary Outcome Measures:
  • Number of Participants With Disease Progression or Death [ Time Frame: Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) ] [ Designated as safety issue: No ]
    Disease progression was defined as at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

  • Progression Free Survival (PFS) [ Time Frame: Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) ] [ Designated as safety issue: No ]
    PFS was defined as the time from enrollment to time of first documented disease progression or death due to any cause, whichever occurred first. Progression: at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. PFS was estimated using Kaplan-Meier methods.

  • Number of Participants With Overall Survival (OS) [ Time Frame: Screening until death (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) ] [ Designated as safety issue: No ]
    OS was defined as the time from enrollment to death from any cause where enrollment was defined as successfully passed screening visit, enrolled in the study and received first dose of study treatment.

  • Overall Survival (OS) [ Time Frame: Screening until death (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) ] [ Designated as safety issue: No ]
    OS was defined as the time from enrollment to death from any cause where enrollment was defined as successfully passed screening visit, enrolled in the study and received first dose of study treatment. OS was estimated using Kaplan-Meier methods.

  • Number of Participants With Time to Progression (TTP) [ Time Frame: Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) ] [ Designated as safety issue: No ]
    TTP was defined as the time from enrollment to first documented disease progression (at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions). TTP was estimated using Kaplan-Meier methods.

  • Time to Progression (TTP) [ Time Frame: Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) ] [ Designated as safety issue: No ]
    TTP was defined as the time from enrollment to first documented disease progression (at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions).

  • Number of Participants With Response [ Time Frame: Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) ] [ Designated as safety issue: No ]
    Participants who had CR or PR were considered as responders. CR: disappearance of all target and non-target lesions and normalization of tumor marker level; PR: at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.

  • Duration of Response (DR) [ Time Frame: Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years) ] [ Designated as safety issue: No ]
    DR was defined as the time from the first recorded response (CR/PR) to the date of first documented progression or death. CR: disappearance of all target lesions and non-target lesions and normalization of tumor marker level. PR: at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. Progression: at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. DR was estimated using Kaplan-Meier methods.


Enrollment: 88
Study Start Date: December 2008
Estimated Study Completion Date: December 2015
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: bevacizumab [Avastin]
15mg/kg iv on day 2 of first 3-week cycle,and on day 1 of subsequent cycles
Drug: capecitabine [Xeloda]
1000mg/m2 bid po on days 1-14 of each 3-week cycle
Drug: trastuzumab [Herceptin]
8mg/kg iv loading dose on day 1 of first 3-week cycle, followed by 6mg/kg iv maintenance dose on day 1 of subsequent cycles

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients, >=18 years of age;
  • breast cancer with measurable locally recurrent or metastatic lesions;
  • candidate for chemotherapy;
  • HER2-positive disease;
  • ECOG PS of <=2.

Exclusion Criteria:

  • previous anticancer therapy for metastatic breast cancer;
  • previous radiotherapy for metastatic breast cancer (except for adjuvant radiotherapy >=6 months before enrollment);
  • chronic daily treatment with corticosteroids (>=10mg/day), aspirin (>325 mg/day) or clopidogrel (>75mg/day);
  • other primary tumor within last 5 years, except for adequately treated cervical cancer in situ, squamous or basal cell skin cancer;
  • uncontrolled hypertension or significant cardiovascular disease.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00811135

Locations
Denmark
Herlev, Denmark, 2730
Vejle, Denmark, 7100
France
Aix En Provence, France, 13616
Beziers, France, 34500
Creteil, France, 94010
Dechy, France, 59187
Lormont, France, 33310
Marseille, France, 13285
Narbonne, France, 11780
Paris, France, 75475
Paris, France, 75571
Paris, France, 75651
Paris, France, 75970
Rodez, France, 12027
Saint Jean, France, 31240
Saint Quentin, France, 02321
Toulouse, France, 31076
Russian Federation
Moscow, Russian Federation, 115478
Moscow, Russian Federation, 143423
Saint-Petersburg, Russian Federation, 197758
Slovakia
Bratislava, Slovakia, 833 10
Spain
Barakaldo, Vizcaya, Spain, 48903
Barcelona, Spain, 08036
Madrid, Spain, 28007
Madrid, Spain, 28040
Malaga, Spain, 29010
Pontevedra, Spain, 36002
Salamanca, Spain, 37007
Sevilla, Spain, 41013
Valencia, Spain, 46010
Valencia, Spain, 46026
Sweden
Eskilstuna, Sweden, 63188
Sundsvall, Sweden, 85186
Uppsala, Sweden, 75185
Vaxjo, Sweden, 35185
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00811135     History of Changes
Other Study ID Numbers: MO21926  2008-003283-20 
Study First Received: December 16, 2008
Results First Received: November 3, 2015
Last Updated: November 3, 2015
Health Authority: Russia: Ministry of Health of the Russian Federation

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bevacizumab
Capecitabine
Trastuzumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 25, 2016