A Biomarker Study in Patients With HER2-negative Metastatic Breast Cancer Treated With Bevacizumab and Paclitaxel (BEVPAC)

A Prospective Randomized Phase II Study to Identify Predictive Biomarkers and Mechanisms of Therapy Resistance in Patients With HER2-negative Metastatic Breast Cancer Treated With the Combination of Bevacizumab and Paclitaxel (BEVPAC).

To explore molecular biomarkers and/or gene expression signatures that predict response to bevacizumab given in combination with paclitaxel as first line therapy in HER2 negative metastatic breast cancer (MBC).

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Bevacizumab; Drug: Paclitaxel

Detailed Description

This is a prospective, randomized, 2-arm, open-label, single-center, phase II trial. A total of 30 patients will be included during a period of 2 years.

The study will be initiated with a non-randomized, feasibility stage including ten patients who will be treated with bevacizumab and paclitaxel, in order to determine the safety of metastatic tumor biopsies during therapy with bevacizumab.

In the second phase, patients will be randomized (1:1) between two treatment arms: A. Bevacizumab + paclitaxel and B. Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Stockholm
    • Solna, Stockholm, Sweden, 17176
      • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-70 years.
2. Performance status ECOG 0-2.
3. Clinically and / or radiologically proven stage IV or recurrent HER2 negative breast cancer.
4. At least one tumor lesion accessible for biopsy. This lesion may not have been treated previously with irradiation.

5. Clinically and/or radiographically documented measurable disease according to RECIST v1.1 criteria. At least one site of disease must be unidimensionally measurable as follows:

   1. CT-scan, physical exam ≥ 10 mm} Chest X-ray ≥ 20 mm }see Eisenhauer et al. for more details
   2. Lymph node short axis ≥ 15 mm }
   3. All radiology studies must be performed within 28 days prior to registration (35 days if negative).

6. Adequate bone-marrow, hepatic and renal function defined as laboratory tests within 7 days prior to enrollment:

   1. Haematology: Absolute granulocytes > 1.5 x 109/L Platelets > 100 x 109/L
   2. Biochemistry:Bilirubin within normal limits Serum creatinine within normal limits
7. APTT and INR within normal limits within 7 days prior to enrollment.
8. Adequate cardiac function with Left Ventricular Ejection Fraction (LVEF) within normal limits determined by echocardiogram or MUGA within 28 days prior to inclusion.
9. Written informed consent must be given.

Exclusion Criteria:

1. Previous systemic treatment for MBC.
2. Major surgery less than 28 days prior to enrollment.
3. Concurrent malignancy of any site, except adequately controlled limited basal cell carcinoma or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix.
4. Bleeding diathesis, history of thromboembolic disease, or ongoing treatment with warfarin, heparin analogs or antiplatelet drugs.
5. Major cardiac comorbidity.
6. Previous treatment with bevacizumab.
7. Previous allergic reaction to taxane analogs.
8. Ongoing pregnancy or lactation.
9. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A; Arm A and feasibility phase: Bevacizumab 15mg/kg administered iv every 3 weeks in combination with paclitaxel 80mg/m2 iv weekly.	Drug: Bevacizumab; 15mg/kg administered iv every 3 weeks in combination with paclitaxel 80mg/m2 iv weekly; Other Names: Avastin; Drug: Paclitaxel; 80mg/m2 iv weekly; Other Names: Taxol; Paxene
Active Comparator: Arm B; Arm B: Paclitaxel 80mg/m2 iv weekly.	Drug: Paclitaxel; 80mg/m2 iv weekly; Other Names: Taxol; Paxene

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of molecular biomarkers	To explore molecular biomarkers and/or gene expression signatures that predict response to bevacizumab given in combination with paclitaxel as first line therapy in HER2 negative MBC.	After the study completion,After completion of the study, which will take up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of metastatic biopsies during bevacizumab therapy	The safety objective of the study is to assess whether carrying out metastatic tissue biopsies during treatment with bevacizumab is safe. For this reason, the study will be initiated with a feasibility phase of 10 patients and will be continued to the randomized phase only if the study specific procedures prove to be safe.	continuous assessment and after inclusion of 10 patients, After completion of the study which will take up to 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular changes by bevacizumab	To identify molecular changes in the tumor induced by the addition of bevacizumab to chemotherapy.	After completion of the study which will take up to 3 years
Efficacy of bevacizumab	To measure the efficacy of bevacizumab in combination with paclitaxel in HER2 negative MBC.	After completion of the study, After completion of the study, which will take up to 3 years

Collaborators and Investigators

• Sponsor: Theodoros Foukakis
• Investigators: Principal Investigator: Theodoros Foukakis, MD PhD, Karolinska University Hospital; Study Director: Jonas Bergh, Professor, Karolinska University Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: October 22, 2012
• First Submitted That Met QC Criteria: November 5, 2012
• First Posted (Estimate): November 7, 2012

Study Record Updates

• Last Update Posted (Actual): February 27, 2019
• Last Update Submitted That Met QC Criteria: February 25, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Metastatic breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Paclitaxel; Bevacizumab
• Other Study ID Numbers: EudraCT no: 2012-003743-30