Pilot Study of Cabazitaxel and Paclitaxel in HER2 Negative Breast Cancer

A Randomised Phase II Pilot Study of 3 Weekly Cabazitaxel Versus Weekly Paclitaxel Chemotherapy in the First Line Treatment of HER2 Negative Breast Cancer

90 patients with HER2 negative breast cancer will be randomised to receive 18 weeks of chemotherapy treatment, either 6 cycles of 3 weekly Cabazitaxel or 6 cycles of weekly Paclitaxel to determine the difference in progression free survival between the 2 groups. If results at that stage suggest a potential benefit then the trial will be developed further to accrue 70 more patients.

This is a prospective multicentre, randomised, open label, study comparing the efficacy and the safety of six 3-weekly cycles cabazitaxel versus 18 x weekly paclitaxel given as first line chemotherapy treatment in patients with HER2-normal metastatic breast cancer. Randomisation will be conducted by a 1:1 ratio.

Inclusion Criteria:

• Written informed consent
• Metastatic breast cancer fit to receive cytotoxic chemotherapy for metastatic disease
• Measurable disease as per RECIST 1.1
• HER2 negative defined as ICH 0+, 1+ or 2+ and FISH/SISH/CISH(ration<2.0) in the case of IHC 2+
• ECOG performance status 0 or 1
• ER+ve or ER-ve
• Female age ≥18 years
• Anticipated life expectancy > 6 months
• Haemoglobin >10.0g/DL
• Absolute neutrophil count>1.5 x 10^9/L
• Platelet count>100 x 10^9/L
• ALT/SGPT<1.5 X ULN
• Serum creatinine <1.5 x ULN
• Negative pregnancy test for all women of child bearing potential

Exclusion Criteria:

• Grade ≥2 oral mucositis or peripheral or sensory neuropathy
• History of other malignancy
• History of severe hypersensitivity ≥grade 3 to polysorbate 80- containing drugs and taxanes
• Clinically significant cardiovascular disease
• Any acute or chronic medical condition
• Acute infection requiring systemic antibiotics or antifungal medication
• Sex hormones
• Administration of any live vaccine within 8 weeks
• Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5
• Participation in another clinical trial with an investigational drug within 30 days of randomisation
• Pregnant or breast feeding women
• Contraindications to the use of corticosteroid treatment
• HER2 Positive breast cancer
• Previous Paclitaxel chemotherapy in the adjuvant setting
• Previous cytotoxic chemotherapy for metastatic disease
• Palliative radiotherapy for metastatic disease within 4 weeks of randomisation
• Symptomatic brain metastases confirmed with CT/MRI brain
• History of other malignancy
• Grade 2