Female patients with HER2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer, who are candidates for chemotherapy. MedDRA version: 12.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer MedDRA version: 12.1 Level: LLT Classification code 10057654 Term: Breast cancer female MedDRA version: 12.1 Level: LLT Classification code 10006187 Term: Breast cancer
Conditions
Interventions
Trade Name: Avastin
Pharmaceutical Form: Solution for infusion
Trade Name: Paclitaxel Fresenius Kabi
Product Name: paclitaxel
Pharmaceutical Form: Intravenous infusion
Trade Name: Myocet
Pharmaceuti
Sponsors
BOOG Study Center
Eligibility
Sex/Gender
All
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 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 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
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; • 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); • 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: •Serum creatinine > 1.5 x ULN •Creatinine clearance 2+. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: •To compare the PFS of second line treatment of 8 continuous cycles of chemotherapy with liposomal doxorubicin (or capecitabine) with 8 cycles of intermittent (2 times 4 cycles) chemotherapy with liposomal doxorubicin (or capecitabine) •To compare the objective Overall Response Rate (ORR) •To compare the Duration of Objective Response (DOR) . For the intermittent chemotherapy schedule the first DOR and, if applicable, second DOR in the same treatment line will be accumulated; •To compare Overall Survival (OS) •To compare the Safety; •To compare the Quality of Life (QoL); •To compare the Pharmacoeconomics . ;Primary end point(s): • 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 death due to any cause. • ORR calculated as the proportion of patients with a best overall response of confirmed Complete Response (CR) and Partial Response (PR). • 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. • 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. • Safety and tolerability. • Changes in the RAND 36 quality of life scale will be measured • Direct medical costs will be calculated using a standard cost method. ;Main Objective: The primary objective of this study is to compare the progression-free survival (PFS) of 8 continuous cycles of chemotherapy (paclitaxel) with 8 cycles of intermittent (2 times 4 cycles) chemotherapy (paclitaxel), both in combination with bevacizumab, in first line treatment of patients with HER2/neu negative, incurable, metastatic or unresectable locally advanced breast cancer. | — |
Countries
Netherlands
Outcome results
None listed