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

Theodoros Foukakis

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Drug: Bevacizumab; Drug: Paclitaxel

Study type: Interventional

Funder types: Other

Identifiers

NCT01722968

EudraCT no: 2012-003743-30

Details and patient eligibility

About

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).

Full 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

Enrollment: 33 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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33 participants in 2 patient groups

Arm A

Active Comparator group

Description:

Arm A and feasibility phase: Bevacizumab 15mg/kg administered iv every 3 weeks in combination with paclitaxel 80mg/m2 iv weekly.

Treatment:

Drug: Paclitaxel

Drug: Bevacizumab

Arm B

Active Comparator group

Description:

Arm B: Paclitaxel 80mg/m2 iv weekly.

Treatment:

Drug: Paclitaxel