Advanced breast cancer
Conditions
Interventions
Trade Name: Avastin
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BEVACIZUMAB
CAS Number: 216974-75-3
Trade Name: Paclitaxel
Pharmaceutical Form: Concentrate for sol
Sponsors
Karolinska University Hospital
Eligibility
Sex/Gender
All
Inclusion 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: CT-scan, physical exam > 10 mm } i. Chest X-ray > 20 mm } see Eisenhauer et al. for more details Lymph node short axis > 15 mm } b. 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: a. Haematology: Absolute granulocytes > 1.5 x 109/L Platelets > 100 x 109/L b. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 Objective: • To determine the safety of performing metastatic tumor biopsies during treatment with bevacizumab (frequency and grade of bleeding complications). In the initial pilot phase of the trial (10 patients), safety evaluation will be the primary objective. • To identify molecular changes in the tumor induced by the addition of bevacizumab to chemotherapy. • To measure the efficacy of bevacizumab in combination with paclitaxel in HER2 negative MBC. ;Primary end point(s): • Frequency and grade (according to NCCTC v. 4.0, see Appendix) of bleeding complications following metastatic lesion core biopsy before the initiation of treatment and FNA during treatment with bevacizumab and paclitaxel. • Efficacy in terms of objective response rate (RR), progression free survival (PFS), and overall survival (OS) will be evaluated (see section 7 “Criteria of Evaluation”) for each patient and its correlation with the potential predictive markers (see section 9) will be explored. ;Timepoint(s) of evaluation of this end point: The safety endpoint will be evaluated continuously while patients are on treatment. The efficacy endpoint will be evaluated every 9 weeks with Computed Tomography. OS will be evaluated continuously. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): None;Timepoint(s) of evaluation of this end point: None | — |
Countries
Sweden
Contacts
Public ContactClinical Trials Unit, Radiumhemmet
Karolinska University Hospital
Outcome results
None listed