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

NCT00773695 | Completed Phase 2

• 1 other identifier: ML21744
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 3

Brief Summary

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).

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Messenger Ribonucleic Acid (mRNA) Markers of Pathological Complete Response, as Assessed by Magnetic Resonance Imaging (MRI)

  Baseline up to end of study treatment (approximately 24 weeks)

Secondary Outcomes (22)

• Percentage of Participants With Objective Pathological Complete Response, as Assessed by Clinical Assessment

  Baseline up to end of study treatment (approximately 24 weeks)

• Percentage of Participants With Type of Surgery

  At Surgery (Between Weeks 24 and 25)

• Percentage of Participants With Axillary Lymph Node Dissection Performed

  At Surgery (Between Weeks 24 and 25)

• Pathological Tumor Size, as Assessed by Histopathological Examination

  At Surgery (Between Weeks 24 and 25)

• Percentage of Participants With Presence of Tumor Cells Close to Resection Margin

  At Surgery (Between Weeks 24 and 25)

Study Arms (4)

Chemotherapy

ACTIVE COMPARATOR

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; Drug: 5-Fluorouracil (5FU); Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Docetaxel

Chemotherapy and Bevacizumab

EXPERIMENTAL

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: Bevacizumab; Drug: Epirubicine; Drug: 5-Fluorouracil (5FU); Drug: Cyclophosphamide; Drug: Paclitaxel; Drug: Docetaxel

Endocrine Therapy

ACTIVE COMPARATOR

Participants will receive aromatase inhibitor therapy at discretion of the investigator for a period of 24 weeks.

Drug: Aromatase Inhibitor

Endocrine Therapy and Bevacizumab

EXPERIMENTAL

Participants will receive aromatase inhibitor therapy at discretion of the investigator and concurrent treatment with bevacizumab for a period of 24 weeks.

Drug: Aromatase Inhibitor; Drug: Bevacizumab

Interventions

Aromatase Inhibitor DRUG

Participants will receive aromatase inhibitor therapy, at a dose per investigator discretion, once daily for 24 weeks.

Endocrine Therapy; Endocrine Therapy and Bevacizumab

Bevacizumab DRUG

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.

Also known as: Avastin

Chemotherapy and Bevacizumab; Endocrine Therapy and Bevacizumab

Epirubicine DRUG

Participants will receive epirubicine at a dose of 100 mg/m\^2 as IV infusion every 3 weeks for 12 weeks.

Chemotherapy; Chemotherapy and Bevacizumab

5-Fluorouracil (5FU) DRUG

Participants will receive 5FU at a dose of 600 mg/m\^2 as IV infusion every 3 weeks for 12 weeks.

Chemotherapy; Chemotherapy and Bevacizumab

Cyclophosphamide DRUG

Participants will receive cyclophosphamide at a dose of 600 mg/m\^2 as IV infusion every 3 weeks for 12 weeks.

Chemotherapy; Chemotherapy and Bevacizumab

Paclitaxel DRUG

Participants will receive paclitaxel at a dose of 80 mg/m\^2 as IV infusion every week for 12 weeks.

Chemotherapy; Chemotherapy and Bevacizumab

Docetaxel DRUG

Participants will receive docetaxel at a dose of 100 mg/m\^2 as IV infusion every 3 weeks for 12 weeks.

Chemotherapy; Chemotherapy and Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \[LVEF\])

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• Norwegian Radium Hospital: collaborator

Study Sites (3)

The Norvegian Radium Hospital Montebello; Dept of Oncology

Oslo, 0379, Norway

Location

Ullevael Sykehus; Dept of Oncology

Oslo, 0407, Norway

Location

St. Olavs Hospital; Kreftavdelingen

Trondheim, 7000, Norway

Location

Related Publications (3)

• Trnkova L, Burikova M, Soltysova A, Ficek A, Plava J, Cumova A, Rojikova L, Jakic K, Sedlackova E, Tichy B, Bystry V, Busato F, Shen Y, Matuskova M, Kucerova L, Oy GF, Maelandsmo GM, Fleischer T, Tost J, Miklikova S, Cihova M, Buocikova V, Smolkova B. Molecular profiling of chemotherapy-resistant breast cancer reveals DNA methylation remodeling associated with the acquisition of paclitaxel resistance. Drug Resist Updat. 2026 Jan 2;85:101350. doi: 10.1016/j.drup.2026.101350. Online ahead of print.

  PMID: 41529624 DERIVED

• Hoglander EK, Nord S, Wedge DC, Lingjaerde OC, Silwal-Pandit L, Gythfeldt HV, Vollan HKM, Fleischer T, Krohn M, Schlitchting E, Borgen E, Garred O, Holmen MM, Wist E, Naume B, Van Loo P, Borresen-Dale AL, Engebraaten O, Kristensen V. Time series analysis of neoadjuvant chemotherapy and bevacizumab-treated breast carcinomas reveals a systemic shift in genomic aberrations. Genome Med. 2018 Nov 29;10(1):92. doi: 10.1186/s13073-018-0601-y.

  PMID: 30497530 DERIVED

• Reinertsen KV, Engebraaten O, Loge JH, Cvancarova M, Naume B, Wist E, Edvardsen H, Wille E, Bjoro T, Kiserud CE. Fatigue During and After Breast Cancer Therapy-A Prospective Study. J Pain Symptom Manage. 2017 Mar;53(3):551-560. doi: 10.1016/j.jpainsymman.2016.09.011. Epub 2016 Dec 29.

  PMID: 28042070 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Aromatase Inhibitors; Bevacizumab; Epirubicin; Fluorouracil; Cyclophosphamide; Paclitaxel; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2008
• First Posted: October 16, 2008
• Study Start: November 7, 2008
• Primary Completion: November 9, 2022
• Study Completion: November 9, 2022
• Last Updated: January 9, 2023

Record last verified: 2023-01

Locations

NO (3)