HER2/neu negative metastatic breast cancer Bevacizumab Paclitaxel Liposomal doxorubicine
Conditions
Interventions
Arm A:
1st line:
1. Paclitaxel and bevacizumab: 8 cycles, unless PD or unacceptable toxicity occurs earlier
2. Bevacizumab until PD or unacceptable toxicity
3. At PD patients will go to the 2nd treatment line.
2nd line:
1. Non-pegylated liposomal doxorubicin (Myocet®) (or capecitabine): 8 cycles, unless PD or unacceptable toxicity occurs earlier
2. At PD patients will go to the 3rd treatment line. If possible, it is advised to cross-over from 2nd line non-pegylated liposomal doxorubicin to 3rd line capecitabine.
Arm B:
1st line:
1. Paclit
3. At PD < 3 months after last administration of paclitaxel patients will go to the 2nd treatment line
4. At PD ≥
3 months after last administration of paclitaxel, patients will receive another 4 cycles of paclitaxel and bevacizumab
5. Bevacizumab until the next PD or unacceptable toxicity
6. At the next PD patients will go to the 2nd treatment line.
2nd line:
1. Non-pegylated liposomal doxorubicin (Myocet®) (or capecitabine): 4 cycles, unless PD or unacceptable toxicity occurs earlie
2. At PD < 3 months patients will go to the 3rd treatment line. If possible, it is advised to cross-over from 2nd line non-pegylated liposomal doxorubicin to 3rd line capecitabine
3. At PD ≥
3 months after last administration of liposomal doxorubicin (Myocet®) (or capecitabine), patients will receive another 4 cycles of liposomal doxorubicin (Myocet®) (or capecitabine)
4. At the next PD patients will go to the 3rd treatment line.
Sponsors
Borstkanker Onderzoek Groep
Eligibility
Inclusion criteria
Inclusion criteria: 1. Female patients ≥ 18 years old; 2. Patients with HER2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer, who are candidates for chemotherapy; 3. Patients with measurable or evaluable-only disease by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria as determined by the investigator; 4. Documented Estrogen Receptor (ER) / Progesteron Receptor (PR) status; 5. HER2/neu-negative disease as determined by immunohistochemistry or Fluorescence In Situ Hybridization (FISH); 6. Patients with an ECOG Performance Status ≤ 2; 7. Life expectancy of > 12 weeks; 8. Signature of Informed Consent Form by patient.
Exclusion criteria
Exclusion criteria: Prior Treatment: 1. Previous chemotherapy for HER2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer; 2. Prior hormonal therapy for HER2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer that has not been discontinued 1 week before start of study treatment; 3. Prior adjuvant/neo-adjuvant chemotherapy within 6 months prior to first study treatment. However, if the prior adjuvant/neo-adjuvant chemotherapy was taxane based, patients are excluded if they received their last chemotherapy within12 months prior to first study treatment; 4. Prior radiotherapy covering more than 30% of marrow-bearing bone; 5. Patients that have received recent radiation therapy that are not recovered from any significant (Grade ≥ 3) acute toxicity prior to study treatment; 6. Prior therapy with bevacizumab, sorafenib, sunitinib, or other VEGF pathway-targeted therapy. Current Treatment: 7. Chronic daily treatment with aspirin (>= 325 mg/day) or clopidogrel (>= 75 mg/day); 8. Chronic daily treatment with corticosteroids (dose of >= 10 mg/day methylprednisolone or equivalent), with the exception of inhaled steroids; 9. Current or recent (within 30 days of first study treatment) treatment with another investigational drug or participation in another investigational study. Hematology, coagulation and biochemistry: 10. Inadequate bone marrow function: Absolute Neutrophil Count (ANC): 2 x the Upper Limit of Normal (ULN) for the institution; B. Aspartaat-Amino-Transferase/ Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT) or Alanine-Amino-Transferase/ Serum Glutamic Pyruvic Transaminase (ALAT/SGPT) > 2.5 x ULN (> 5 x ULN in patients with liver metastases); C. Alkaline phosphatase levels > 2.5 x ULN (> 5 x ULN in patients with liver metastases, or > 10 x ULN in patients with bone metastases). 12. Inadequate renal function, defined as: A. Serum creatinine > 1.5 x ULN; B. Creatinine clearance 2+. Patients with >= 2+ proteinuria on dipstick analysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤1g of protein in the 24-hour urine. 13. Patients not receiving anticoagulant medication who have an International Normalized Ratio (INR) > 1.5 or an activated Partial Thromboplastin Time (aPTT) > 1.5 x ULN within 7 days prior to first study treatment. Note: Patients receiving full dose oral or parenteral anticoagulants may be included in the study as long as anticoagulant dosing has been stable for at least two weeks prior to study entry and the appropriate coagulation monitoring tests are within local therapeutic limits. Other: 14. Known CNS disease, except for treated brain metastases. Treated brain metastases are defined as: having no evidence of progression or haemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LI
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PFS is defined as the time from start of treatment to the documented progression that requires the patient to switch to the next treatment line or to death due to any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Changes in the RAND 36 quality of life scale will be measured; 2. Safety and tolerability; 3. ORR calculated as the proportion of patients with a best overall response of confirmed Complete Response (CR) and Partial Response (PR); 4. DOR calculated as the time from the date of first documented CR or PR to the first documented progression or death due to underlying cancer; 5. OS calculated as the time from the date of randomization to the date of death due to any cause or the date of last contact; 6. Direct medical costs will be calculated using a standard cost method. | — |
Contacts
Public ContactBorstkanker Onderzoek Groep (BOOG)
Plesmanlaan 125
Outcome results
None listed