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

Phase 2

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Bevacizumab; Drug: Paclitaxel

• Registration Number: NCT01722968
• Lead Sponsor: Theodoros Foukakis

Brief Summary

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).

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 Timeline

• Study First Submitted: 2012-10-22
• Study Start: 2012-11
• Study First Submitted QC: 2012-11-05
• Study First Posted: 2012-11-07
• Primary Completion: 2018-06
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-25
• Last Update Posted: 2019-02-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Identification of molecular biomarkers	After the study completion,After completion of the study, which will take up to 3 years	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.

Secondary Outcome Measures

Name	Time	Method
Safety of metastatic biopsies during bevacizumab therapy	continuous assessment and after inclusion of 10 patients, After completion of the study which will take up to 1 year	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.

Trial Locations

Locations (1)

Karolinska University Hospital; 🇸🇪 Solna, Stockholm, Sweden