Locally recurrent or metastatic breast cancer patients with HER2/neu negative tumor
Conditions
Interventions
Arm A (cycles of 28 days):
• Bevacizumab: 10 mg/kg i.v. on day 1 and day 15
• Paclitaxel: 90 mg/m2 i.v. on days 1, 8 and 15
Arm B (cycles of 21 days):
• Bevacizumab: 15 mg/kg i.v. on day 1
• Pac
Sponsors
VU University medical center
Prof. E. Boven, MD, PhD, medical oncologist
De Boelelaan 1117
1081 HV Amsterdam
Phone: 020-444 4336
E-mail: e.boven@vumc.nl
together with:
Borstkanker Onderzoek Groep(BOOG)
Dr. A.E. van Leeuwen-Stok, research-manager
P.O. Box 9236, 1006 AE Amsterdam
Phone: 020-346 2547
Fax: 020-346 2525
E-mail: boog@ikca.nl
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patients with histologically or cytologically confirmed, HER2/neu-negative, pre- or postmenopausal adenocarcinoma of the breast with measurable or non-measurable locally recurrent or metastatic disease, who are candidates for chemotherapy. Locally recurrent disease must not be amenable to resection and/or radiotherapy with curative intent. 2. Documented ER/PR status 3. HER2/neu-negative disease as determined by immunohistochemistry or FISH/CISH 4. Prior adjuvant chemotherapy is allowed provided that the last dose of chemotherapy was not within 6 months (not within 12 months if taxane-based) prior to randomization. 5. Prior maximum cumulative dose must not exceed 360 mg/m2 for doxorubicin and 720 mg/m2 for epirubicin 6. Female only 7. Age > 18 years and ≤ 75 years 8. ECOG PS of 0 or 1 9. Life expectancy of > 12 weeks 10. Able to comply with the protocol 11. Written informed consent (Informed Consent document to be approved by the institution’s Independent Ethics Committee [IEC]) obtained prior to any study specific screening
Exclusion criteria
Exclusion criteria: * Previous treatment • Previous chemotherapy for locally recurrent or metastatic breast cancer • Prior hormonal therapy for locally recurrent or metastatic disease should have been discontinued at least 2 weeks before randomization. • Patients with bone metastases only are allowed provided that they are on bisphosphonate treatment > 3 months. - Patients who have received adjuvant radiotherapy as part of the treatment of early breast cancer are eligible if the last fraction of radiotherapy was administered at least 6 months prior to randomization. Radiotherapy administered for the relief of metastatic bone pain is allowed prior to study entry, but • no more than 30% of marrow-bearing bone should have been irradiated • the last fraction of radiotherapy should not have been administered within 3 weeks prior to randomization. - Other primary tumors within the last 5 years before inclusion, except for adequately controlled basal cell carcinoma of the skin, or carcinoma in situ of the cervix * Neurological signs and symptoms - Previous or current CNS metastases. A CT or MRI of the brain must be performed within 4 weeks prior to randomization if the presence of metastases at this site is suspected. - History or evidence upon physical/neurological examination of CNS disease unrelated to cancer, unless adequately treated with standard medical therapy e.g. uncontrolled seizures. - Pre-existing peripheral neuropathy ≥ NCI-CTC (version 3.0) grade 1 at randomization * Hematology, coagulation and biochemistry - Inadequate bone marrow function: ANC: 1.5 x ULN and/or aPTT > 1.5 x ULN within 7 days prior to randomization - Inadequate liver function: • Serum (total) bilirubin above the normal limit for the institution, and or • ASAT & ALAT > 2.5 x ULN ( > 5 x ULN in patients with liver metastases) Patients are not eligible for the study if they have ASAT/ALAT levels > 1.5 x ULN concurrent with: - serum alkaline phosphatase levels of > 2.5 x ULN at baseline or - ASAT/ALAT > ULN concurrent with alkaline phosphatase > 6 x ULN - Inadequate renal function: • Serum creatinine > 177 µmol/L or calculated creatinine clearance 325 mg/day) or clopidogrel (> 75 mg/day). No therapeutic treatment with LMWH or oral anticoagulants. Prophylactic doses of LMWH are allowed. - History or evidence or inherited bleeding diathesis or coagulopathy with the risk of bleeding - History of cerebrovascular accident - Arterial or venous thrombosis ≤ 12 months prior to registration - Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: CVA/stroke (≤ 6 months prior to randomization), myocar
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary objective: To investigate Progression Free Survival (PFS) in patients randomized to: -bevacizumab 10 mg/kg q2wk + paclitaxel 90 mg/m2 on days 1, 8 and 15 of a 4-week cycle versus -bevacizumab 15 mg/kg day 1 + paclitaxel 90 mg/m2 on days 1 and 8 + capecitabine 825 mg/m2 orally twice daily on days 1-14 of a 3-week cycle | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objectives: To determine: - Overall RR, duration of response and overall survival - Safety | — |
Contacts
Public ContactBorstkanker Onderzoek Groep (BOOG)
Plesmanlaan 125
Outcome results
None listed