Pilot Study of Cabazitaxel and Paclitaxel in HER2 Negative Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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HER2 Negative Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Cabazitaxel
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cabazitaxel<br>6 cycles of cabazitaxel intravenous chemotherapy 25mg/m2 on day 1 of each 21 day cycle | Drug: Cabazitaxel<br>* 3 weekly cyctotoxic chemotherapy<br>* Other names: Jevtana;|
| Active Comparator: Paclitaxel<br>6 cycles of Paclitaxel intravenous chemotherapy 80mg/m2 on days 1,8 and 15 of each 21 day cycle. | Drug: Paclitaxel<br>* Weekly cyctotoxic chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Duration of progression free survival | Defined as the time from randomisation to either disease progression or death from any cause, whichever came first, assessed up to 5 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit rate | Defined as stable disease rate + partial response rate+complete response rate according to RECIST 1.1 criteria | At the completion of 6 cycles of chemotherapy, which is after 18 weeks | 
| Objective response rate | Defined as complete and partial response recorded from the start of treatment to completion of 6 cycles of treatment. | At completion of 6 cycles of chemotherapy, which is after 18 weeks. | 
| Overall survival | Survival duration from randomisation to date of death. | Determined as the time from randomisation to death from any cause. Average survival rates for this population may be approximately 18 months. | 
| Time to next chemotherapy treatment | time from randomisation to another chemotherapy treatment after confirmed progression. | Measured from from the date of the last day of trial treatment. approximately after progression which on average would be after 12 months. | 
| Time to response | Time taken for tumour burden to respond to treatment | Determined by time from randomisation to radiological partial response, usually within the 6 cycles of treatment, therefore wihtin 18 weeks. | 
| Quality of life as measured by patients themselves | 2 Quality of life questionnaires | EQ5D-5L and FACT B will be completed at baseline, prior to cycles 3 and 5 and at the end of treatment visit, therefore within approximately 21 weeks from randomisation | 
| Number of adverse events and Number of participants with adverse events per arm and the grade of AEs | CTCAE Version 4.0 graded AEs | Form the date of consent to 30 days after trial treatment has stopped. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, HER2 negative, Cabazitaxel, Paclitaxel, Chemotherapy