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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00773695
• Other study ID #: ML21744
• Status: Completed
• Phase: Phase 2
• Start date: November 7, 2008
• Est. completion date: November 9, 2022

Study information

• Verified date: January 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: November 9, 2022
• Est. primary completion date: November 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Aromatase Inhibitor
Participants will receive aromatase inhibitor therapy, at a dose per investigator discretion, once daily for 24 weeks.
• 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.
• Epirubicine
Participants will receive epirubicine at a dose of 100 mg/m^2 as IV infusion every 3 weeks for 12 weeks.
• 5-Fluorouracil (5FU)
Participants will receive 5FU at a dose of 600 mg/m^2 as IV infusion every 3 weeks for 12 weeks.
• Cyclophosphamide
Participants will receive cyclophosphamide at a dose of 600 mg/m^2 as IV infusion every 3 weeks for 12 weeks.
• Paclitaxel
Participants will receive paclitaxel at a dose of 80 mg/m^2 as IV infusion every week for 12 weeks.
• Docetaxel
Participants will receive docetaxel at a dose of 100 mg/m^2 as IV infusion every 3 weeks for 12 weeks.

Locations

Country	Name	City	State
Norway	The Norvegian Radium Hospital Montebello; Dept of Oncology	Oslo
Norway	Ullevael Sykehus; Dept of Oncology	Oslo
Norway	St. Olavs Hospital; Kreftavdelingen	Trondheim

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Norwegian Radium Hospital

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of Participants With Objective Pathological Complete Response, as Assessed by Clinical Assessment		Baseline up to end of study treatment (approximately 24 weeks)
Secondary	Percentage of Participants With Type of Surgery	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)
Secondary	Percentage of Participants With Axillary Lymph Node Dissection Performed		At Surgery (Between Weeks 24 and 25)
Secondary	Pathological Tumor Size, as Assessed by Histopathological Examination		At Surgery (Between Weeks 24 and 25)
Secondary	Percentage of Participants With Presence of Tumor Cells Close to Resection Margin		At Surgery (Between Weeks 24 and 25)
Secondary	Percentage of Participants With Tumor Deposit in Other Body Parts		At Surgery (Between Weeks 24 and 25)
Secondary	Tumor Free Resection Margin		At Surgery (Between Weeks 24 and 25)
Secondary	Pathological Tumor Size as Measure Using Caliper		Cycles 1 to 10 (cycle length=21 days), and Week 25
Secondary	Pathological Tumor Size as Measure Using MRI		Baseline, Weeks 12 and 25
Secondary	Pathological Tumor Size as Measure Using Mamography		Baseline, Weeks 12 and 25
Secondary	Pathological Breast Tumor Size as Measure Using Ultrasound		Baseline, Weeks 12 and 25
Secondary	Pathological Axilla Tumor Size as Measure Using Ultrasound		Baseline, Weeks 12 and 25
Secondary	Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status		Screening, Cycles 1 to 10 (cycle length=21 days), and Week 25
Secondary	Percentage of Participants With Lymph Node Involvement		Cycles 1 to 10 (cycle length=21 days), and Week 25
Secondary	Percentage of Participants With Objective Tumor Response, as Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST)		Weeks 12 and 25
Secondary	Percentage of Participants With New Lesions		Weeks 12 and 25
Secondary	Percentage of Participants With Molecular Changes in Protein Kinase Expression		Baseline up to end of study treatment (approximately 24 weeks)
Secondary	Percentage of Participants With Molecular Changes in Messenger Ribonucleic Acid (mRNA)/microRNA(miRNA)		Baseline up to end of study treatment (approximately 24 weeks)
Secondary	Percentage of Participants With Molecular Changes in Protein Expression		Baseline up to end of study treatment (approximately 24 weeks)
Secondary	Percentage of Participants With Single Nucleotide Polymorphism (SNP) Profiles Predicting Treatment Response		Baseline up to end of study treatment (approximately 24 weeks)
Secondary	Percentage of Participants With Treatment-Induced Changes in Tumor Cells as Determined by Number of Disseminated Tumor Cells in Bone Marrow		Baseline up to end of study treatment (approximately 24 weeks)
Secondary	Percentage of Participants With Treatment-Induced Changes in Tumor Cells as Determined by Number of Circulating Tumor Cells in Peripheral Blood		Baseline up to end of study treatment (approximately 24 weeks)