A Study of Avastin (Bevacizumab) in Patients With Inflammatory or Locally Advanced Breast Cancer

Phase II, Open Label, Neoadjuvant Study of Bevacizumab in Patients With Inflammatory or Locally Advanced Breast Cancer

This single arm study will assess the efficacy and safety of sequential neoadjuvant chemotherapy and bevacizumab (Avastin), before surgery and/or radiotherapy, in participants with inflammatory or locally advanced operable breast cancer. Participants will receive 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC), followed by paclitaxel, given concomitantly with bevacizumab. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: 5-fluorouracil; Drug: Epidoxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel; Biological: Bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
  • Emilia-Romagna
    • Reggio Emilia, Emilia-Romagna, Italy, 42100
  • Friuli-Venezia Giulia
    • Pordenone, Friuli-Venezia Giulia, Italy, 33170
  • Liguria
    • Genova, Liguria, Italy, 16132
  • Lombardia
    • Mantova, Lombardia, Italy, 46100
  • Piemonte
    • Cuneo, Piemonte, Italy, 12100
    • Torino, Piemonte, Italy, 10126
  • Veneto
    • Negrar, Veneto, Italy, 37024

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• female participants, >=18 years of age;
• stage III, or inflammatory breast cancer;
• estrogen receptor/progesterone receptor (ER/PgR) positive or negative and human epidermal growth factor receptor 2 (HER-2) negative;
• normal left ventricular ejection fraction (LVEF).

Exclusion Criteria:

• previous chemotherapy/endocrine therapy;
• evidence of distant metastatic disease;
• other primary tumors in last 5 years (except for adequately treated cancer in situ of the cervix, or basal cell skin cancer);
• chronic daily treatment with >325 milligram per day (mg/day) aspirin, or >75mg/day clopidogrel.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Bevacizumab; Participants will receive FEC, followed by paclitaxel, given concomitantly with bevacizumab for approximately 3-12 months.

Drug: 5-fluorouracil; 600 milligrams per meter squared (mg/m^2) as an intravenous (i.v.) bolus over ≤15 minutes every 3 weeks for 4 cycles.; Drug: Epidoxorubicin; 90 mg/m^2 as an i.v. infusion over 1 hour every 3 weeks for 4 cycles.; Drug: Cyclophosphamide; 600 mg/m^2 as an i.v. infusion over 1 hour every 3 weeks for 4 cycles.; Drug: Paclitaxel; Paclitaxel was administered at 80 mg/m^2 i.v. over 1 hour weekly for 12 weeks.; Biological: Bevacizumab; Bevacizumab was administered at 10 milligrams per kilogram (mg/kg) i.v. every 2 weeks for 6 cycles.; Other Names: Avastin®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Pathological Complete Response Following Principle Investigator Review	Pathological complete response was defined as absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy.	Up to 7.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Objective response rate was defined as the percentage of participants with a Complete Response (CR) or Partial Response (PR) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). CR was defined as the disappearance of all target lesions; PR was defined as a 30% decrease in sum of longest diameter of target lesions.	Up to 7.5 years
Percentage of Participants With Breast-Conserving Surgery	Rate of breast conversing surgery is defined as percentage of participants who achieved breast conversing surgery out of the ITT population without inflammatory breast cancer, as these participants received mastectomy irrespective of their response to neoadjuvant treatment.	Up to 7.5 years
Percentage of Participants With Disease-Free Interval	Disease-free interval was defined as the time from enrollment until recurrence of tumor or death from any cause, and was estimated using the Kaplan-Meier method. The percentage of participants without events at Months 12, 24, 36, 48, and 60 is presented.	Months 12, 24, 36, 48, and 60
Overall Survival	Overall survival was defined as the time from enrollment of participant to death from any cause.	Up to 7.5 years
Percentage of Participants Experiencing Any Adverse Event	An adverse event was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Up to 7.5 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Clavarezza M, Turazza M, Aitini E, Saracchini S, Garrone O, Durando A, De Placido S, Bisagni G, Levaggi A, Bighin C, Restuccia E, Scalamogna R, Galli A, Del Mastro L. Phase II open-label study of bevacizumab combined with neoadjuvant anthracycline and taxane therapy for locally advanced breast cancer. Breast. 2013 Aug;22(4):470-5. doi: 10.1016/j.breast.2013.03.012. Epub 2013 May 1.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: November 15, 2007
• First Submitted That Met QC Criteria: November 15, 2007
• First Posted (Estimate): November 16, 2007

Study Record Updates

• Last Update Posted (Actual): April 9, 2018
• Last Update Submitted That Met QC Criteria: September 12, 2017
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Paclitaxel; Fluorouracil; Epirubicin; Bevacizumab
• Other Study ID Numbers: ML19884; 2006-003291-35 (EudraCT Number)