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

NCT ID: NCT00773695

Last Updated: 2023-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-07
• Study Completion Date: 2022-11-09

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Epirubicine

Intervention Type: DRUG

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

5-Fluorouracil (5FU)

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Paclitaxel

Intervention Type: DRUG

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

Docetaxel

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: 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.

Epirubicine

Intervention Type: DRUG

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

5-Fluorouracil (5FU)

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Paclitaxel

Intervention Type: DRUG

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

Docetaxel

Intervention Type: DRUG

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

Endocrine Therapy

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

Group Type: ACTIVE_COMPARATOR

Aromatase Inhibitor

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Aromatase Inhibitor

Intervention Type: DRUG

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

Bevacizumab

Intervention Type: 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.

Interventions

Aromatase Inhibitor

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

Intervention Type: 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.

Intervention Type: DRUG

Epirubicine

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

Intervention Type: 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.

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: DRUG

Paclitaxel

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

Intervention Type: DRUG

Docetaxel

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

Intervention Type: DRUG

Other Intervention Names

Avastin

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Norwegian Radium Hospital

OTHER

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

The Norvegian Radium Hospital Montebello; Dept of Oncology

Oslo, , Norway

Ullevael Sykehus; Dept of Oncology

Oslo, , Norway

St. Olavs Hospital; Kreftavdelingen

Trondheim, , Norway

Countries

Norway

References

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.

Reference Type: DERIVED

PMID: 30497530 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28042070 (View on PubMed)

Other Identifiers

ML21744

Identifier Type: -

Identifier Source: org_study_id