Clinical trial NCT01722968: A Biomarker Study in Patients With HER2-negative Metastatic Breast Cancer Treated With Bevacizumab and Paclitaxel
Official title: 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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Metastatic breast cancer
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
First posted: 2012-11-07
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Identification of molecular biomarkers
timeFrame: After the study completion,After completion of the study, which will take up to 3 years
Secondary outcomes:
measure: Safety of metastatic biopsies during bevacizumab therapy
timeFrame: continuous assessment and after inclusion of 10 patients, After completion of the study which will take up to 1 year
Other outcomes:
measure: Molecular changes by bevacizumab
timeFrame: After completion of the study which will take up to 3 years
measure: Efficacy of bevacizumab
timeFrame: After completion of the study, After completion of the study, which will take up to 3 years
Locations:
city: Solna
country: Sweden
facility: Karolinska University Hospital
state: Stockholm
Study officials:
affiliation: Karolinska University Hospital
name: Theodoros Foukakis, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Karolinska University Hospital
name: Jonas Bergh, Professor
role: STUDY_DIRECTOR
References: