A Study of Bevacizumab (Avastin) in Combination With Neoadjuvant Treatment Regimens in Participants With Primary Human Epidermal Growth Factor Receptor 2 (HER2) Negative Breast Cancer

January 5, 2023 updated by: Hoffmann-La Roche

A Multicenter, Randomized, Phase II Clinical Trial to Evaluate the Effect of Avastin in Combination With Neoadjuvant Treatment Regimens on the Molecular and Metabolic Characteristics and Changes in the Primary Tumors With Reference to the Obtained Responses in Patients With Large Primary HER2 Negative Breast Cancers

This study will evaluate the effect of bevacizumab in combination with chemotherapy or endocrine therapy, as preoperative treatment, in participants with HER2 negative breast cancer. Participants will be randomized to receive either chemotherapy (FEC100: Epirubicine 100 milligrams per square meter [mg/m^2], 5-fluorouracil 600 mg/m^2, and cyclophosphamide 600 mg/m^2] for 12 weeks followed by taxane (paclitaxel/docetaxel) for 12 weeks or endocrine therapy (an aromatase inhibitor] daily for 24 weeks) with or without bevacizumab (15 milligrams per kilogram [mg/kg] as intravenous [IV] infusion every 3 weeks up 24 weeks).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
150

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Norway
      • Oslo, Norway, 0379
        • The Norvegian Radium Hospital Montebello; Dept of Oncology
      • Oslo, Norway, 0407
        • Ullevael Sykehus; Dept of Oncology
      • Trondheim, Norway, 7000
        • St. Olavs Hospital; Kreftavdelingen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically or cytologically confirmed, HER2-negative, men or pre- or post-menopausal women with primary operable adenocarcinoma of the breast, greater than or equal to (>=) 2.5 centimeters (cm) in size
  • Eastern Cooperative Oncology Group (ECOG)/world health organization (WHO) performance status less than or equal to (</=) 2
  • Normal baseline cardiac function (Left Ventricular Ejection Fraction [LVEF])

Exclusion Criteria:

  • Stage IV (metastatic) disease
  • Previous treatment for localized breast cancer less than (<) 24 months from diagnosis of present breast cancer
  • Other previous or current cancer except for basal cell cancer or in situ cervical cancer
  • Current or recent use of aspirin (greater than [>] 325 milligrams per day)
  • Clinically significant cardiovascular disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Chemotherapy
Participants will receive epirubicine, 5-fluorouracil, and cyclophosphamide (FEC 100) for 12 weeks followed by taxane therapy (paclitaxel or docetaxel) for next 12 weeks.
Drug: Epirubicine
Participants will receive epirubicine at a dose of 100 mg/m^2 as IV infusion every 3 weeks for 12 weeks.
Drug: 5-Fluorouracil (5FU)
Participants will receive 5FU at a dose of 600 mg/m^2 as IV infusion every 3 weeks for 12 weeks.
Drug: Cyclophosphamide
Participants will receive cyclophosphamide at a dose of 600 mg/m^2 as IV infusion every 3 weeks for 12 weeks.
Drug: Paclitaxel
Participants will receive paclitaxel at a dose of 80 mg/m^2 as IV infusion every week for 12 weeks.
Drug: Docetaxel
Participants will receive docetaxel at a dose of 100 mg/m^2 as IV infusion every 3 weeks for 12 weeks.
Experimental: Chemotherapy and Bevacizumab
Participants will receive epirubicine, 5-fluorouracil, and cyclophosphamide (FEC 100) for 12 weeks followed by taxane therapy (paclitaxel or docetaxel) for next 12 weeks. Participants will also receive concurrent treatment with bevacizumab every 3 weeks for 24 weeks.
Drug: Epirubicine
Participants will receive epirubicine at a dose of 100 mg/m^2 as IV infusion every 3 weeks for 12 weeks.
Drug: 5-Fluorouracil (5FU)
Participants will receive 5FU at a dose of 600 mg/m^2 as IV infusion every 3 weeks for 12 weeks.
Drug: Cyclophosphamide
Participants will receive cyclophosphamide at a dose of 600 mg/m^2 as IV infusion every 3 weeks for 12 weeks.
Drug: Paclitaxel
Participants will receive paclitaxel at a dose of 80 mg/m^2 as IV infusion every week for 12 weeks.
Drug: Docetaxel
Participants will receive docetaxel at a dose of 100 mg/m^2 as IV infusion every 3 weeks for 12 weeks.
Drug: Bevacizumab
Bevacizumab will be administered at a dose of 15 mg/kg as IV infusion every 3 weeks (or 10 mg/kg every other week in participants receiving weekly paclitaxel), for 24 weeks.
Other Names:
  • Avastin
Active Comparator: Endocrine Therapy
Participants will receive aromatase inhibitor therapy at discretion of the investigator for a period of 24 weeks.
Drug: Aromatase Inhibitor
Participants will receive aromatase inhibitor therapy, at a dose per investigator discretion, once daily for 24 weeks.
Experimental: Endocrine Therapy and Bevacizumab
Participants will receive aromatase inhibitor therapy at discretion of the investigator and concurrent treatment with bevacizumab for a period of 24 weeks.
Drug: Bevacizumab
Bevacizumab will be administered at a dose of 15 mg/kg as IV infusion every 3 weeks (or 10 mg/kg every other week in participants receiving weekly paclitaxel), for 24 weeks.
Other Names:
  • Avastin
Drug: Aromatase Inhibitor
Participants will receive aromatase inhibitor therapy, at a dose per investigator discretion, once daily for 24 weeks.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Percentage of Participants With Messenger Ribonucleic Acid (mRNA) Markers of Pathological Complete Response, as Assessed by Magnetic Resonance Imaging (MRI)
Time Frame: Baseline up to end of study treatment (approximately 24 weeks)
Baseline up to end of study treatment (approximately 24 weeks)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Objective Pathological Complete Response, as Assessed by Clinical Assessment
Time Frame: Baseline up to end of study treatment (approximately 24 weeks)
Baseline up to end of study treatment (approximately 24 weeks)
Percentage of Participants With Type of Surgery
Time Frame: At Surgery (Between Weeks 24 and 25)
Percentage of participants with different surgery types (for example, Mastectomy, Tumorectomy/Breast conserving therapy (BCT), and Tumorectomy followed by mastectomy) will be reported.
At Surgery (Between Weeks 24 and 25)
Percentage of Participants With Axillary Lymph Node Dissection Performed
Time Frame: At Surgery (Between Weeks 24 and 25)
At Surgery (Between Weeks 24 and 25)
Pathological Tumor Size, as Assessed by Histopathological Examination
Time Frame: At Surgery (Between Weeks 24 and 25)
At Surgery (Between Weeks 24 and 25)
Percentage of Participants With Presence of Tumor Cells Close to Resection Margin
Time Frame: At Surgery (Between Weeks 24 and 25)
At Surgery (Between Weeks 24 and 25)
Percentage of Participants With Tumor Deposit in Other Body Parts
Time Frame: At Surgery (Between Weeks 24 and 25)
At Surgery (Between Weeks 24 and 25)
Tumor Free Resection Margin
Time Frame: At Surgery (Between Weeks 24 and 25)
At Surgery (Between Weeks 24 and 25)
Pathological Tumor Size as Measure Using Caliper
Time Frame: Cycles 1 to 10 (cycle length=21 days), and Week 25
Cycles 1 to 10 (cycle length=21 days), and Week 25
Pathological Tumor Size as Measure Using MRI
Time Frame: Baseline, Weeks 12 and 25
Baseline, Weeks 12 and 25
Pathological Tumor Size as Measure Using Mamography
Time Frame: Baseline, Weeks 12 and 25
Baseline, Weeks 12 and 25
Pathological Breast Tumor Size as Measure Using Ultrasound
Time Frame: Baseline, Weeks 12 and 25
Baseline, Weeks 12 and 25
Pathological Axilla Tumor Size as Measure Using Ultrasound
Time Frame: Baseline, Weeks 12 and 25
Baseline, Weeks 12 and 25
Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
Time Frame: Screening, Cycles 1 to 10 (cycle length=21 days), and Week 25
Screening, Cycles 1 to 10 (cycle length=21 days), and Week 25
Percentage of Participants With Lymph Node Involvement
Time Frame: Cycles 1 to 10 (cycle length=21 days), and Week 25
Cycles 1 to 10 (cycle length=21 days), and Week 25
Percentage of Participants With Objective Tumor Response, as Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: Weeks 12 and 25
Weeks 12 and 25
Percentage of Participants With New Lesions
Time Frame: Weeks 12 and 25
Weeks 12 and 25
Percentage of Participants With Molecular Changes in Protein Kinase Expression
Time Frame: Baseline up to end of study treatment (approximately 24 weeks)
Baseline up to end of study treatment (approximately 24 weeks)
Percentage of Participants With Molecular Changes in Messenger Ribonucleic Acid (mRNA)/microRNA(miRNA)
Time Frame: Baseline up to end of study treatment (approximately 24 weeks)
Baseline up to end of study treatment (approximately 24 weeks)
Percentage of Participants With Molecular Changes in Protein Expression
Time Frame: Baseline up to end of study treatment (approximately 24 weeks)
Baseline up to end of study treatment (approximately 24 weeks)
Percentage of Participants With Single Nucleotide Polymorphism (SNP) Profiles Predicting Treatment Response
Time Frame: Baseline up to end of study treatment (approximately 24 weeks)
Baseline up to end of study treatment (approximately 24 weeks)
Percentage of Participants With Treatment-Induced Changes in Tumor Cells as Determined by Number of Disseminated Tumor Cells in Bone Marrow
Time Frame: Baseline up to end of study treatment (approximately 24 weeks)
Baseline up to end of study treatment (approximately 24 weeks)
Percentage of Participants With Treatment-Induced Changes in Tumor Cells as Determined by Number of Circulating Tumor Cells in Peripheral Blood
Time Frame: Baseline up to end of study treatment (approximately 24 weeks)
Baseline up to end of study treatment (approximately 24 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Norwegian Radium Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 7, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 9, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 9, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 15, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 15, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 16, 2008

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 9, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 5, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ML21744

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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