Clinical trial NCT00773695: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
Collaborators: name: Norwegian Radium Hospital
First posted: 2008-10-16
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Percentage of Participants With Messenger Ribonucleic Acid (mRNA) Markers of Pathological Complete Response, as Assessed by Magnetic Resonance Imaging (MRI)
timeFrame: Baseline up to end of study treatment (approximately 24 weeks)
Secondary outcomes:
measure: Percentage of Participants With Objective Pathological Complete Response, as Assessed by Clinical Assessment
timeFrame: Baseline up to end of study treatment (approximately 24 weeks)
measure: Percentage of Participants With Type of Surgery
timeFrame: At Surgery (Between Weeks 24 and 25)
measure: Percentage of Participants With Axillary Lymph Node Dissection Performed
timeFrame: At Surgery (Between Weeks 24 and 25)
measure: Pathological Tumor Size, as Assessed by Histopathological Examination
timeFrame: At Surgery (Between Weeks 24 and 25)
measure: Percentage of Participants With Presence of Tumor Cells Close to Resection Margin
timeFrame: At Surgery (Between Weeks 24 and 25)
measure: Percentage of Participants With Tumor Deposit in Other Body Parts
timeFrame: At Surgery (Between Weeks 24 and 25)
measure: Tumor Free Resection Margin
timeFrame: At Surgery (Between Weeks 24 and 25)
measure: Pathological Tumor Size as Measure Using Caliper
timeFrame: Cycles 1 to 10 (cycle length=21 days), and Week 25
measure: Pathological Tumor Size as Measure Using MRI
timeFrame: Baseline, Weeks 12 and 25
measure: Pathological Tumor Size as Measure Using Mamography
timeFrame: Baseline, Weeks 12 and 25
measure: Pathological Breast Tumor Size as Measure Using Ultrasound
timeFrame: Baseline, Weeks 12 and 25
measure: Pathological Axilla Tumor Size as Measure Using Ultrasound
timeFrame: Baseline, Weeks 12 and 25
measure: Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
timeFrame: Screening, Cycles 1 to 10 (cycle length=21 days), and Week 25
measure: Percentage of Participants With Lymph Node Involvement
timeFrame: Cycles 1 to 10 (cycle length=21 days), and Week 25
measure: Percentage of Participants With Objective Tumor Response, as Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Weeks 12 and 25
measure: Percentage of Participants With New Lesions
timeFrame: Weeks 12 and 25
measure: Percentage of Participants With Molecular Changes in Protein Kinase Expression
timeFrame: Baseline up to end of study treatment (approximately 24 weeks)
measure: Percentage of Participants With Molecular Changes in Messenger Ribonucleic Acid (mRNA)/microRNA(miRNA)
timeFrame: Baseline up to end of study treatment (approximately 24 weeks)
measure: Percentage of Participants With Molecular Changes in Protein Expression
timeFrame: Baseline up to end of study treatment (approximately 24 weeks)
measure: Percentage of Participants With Single Nucleotide Polymorphism (SNP) Profiles Predicting Treatment Response
timeFrame: Baseline up to end of study treatment (approximately 24 weeks)
measure: Percentage of Participants With Treatment-Induced Changes in Tumor Cells as Determined by Number of Disseminated Tumor Cells in Bone Marrow
timeFrame: Baseline up to end of study treatment (approximately 24 weeks)
measure: Percentage of Participants With Treatment-Induced Changes in Tumor Cells as Determined by Number of Circulating Tumor Cells in Peripheral Blood
timeFrame: Baseline up to end of study treatment (approximately 24 weeks)
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: The Norvegian Radium Hospital Montebello; Dept of Oncology
city: Oslo
country: Norway
facility: Ullevael Sykehus; Dept of Oncology
city: Trondheim
country: Norway
facility: St. Olavs Hospital; Kreftavdelingen
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.