Clinical trial NCT03048942: Pilot Study of Cabazitaxel and Paclitaxel in HER2 Negative Breast Cancer
Official title: A Randomised Phase II Pilot Study of 3 Weekly Cabazitaxel Versus Weekly Paclitaxel Chemotherapy in the First Line Treatment of HER2 Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: HER2 Negative Metastatic Breast Cancer
Keywords: Breast cancer
HER2 negative
Cabazitaxel
Paclitaxel
Chemotherapy
Lead sponsor: University Hospitals Bristol and Weston NHS Foundation Trust
Sponsor class: OTHER
First posted: 2017-02-09
Enrollment: 160
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: Defined as the time from randomisation to either disease progression or death from any cause, whichever came first, assessed up to 5 years.
Secondary outcomes:
measure: Clinical benefit rate
timeFrame: At the completion of 6 cycles of chemotherapy, which is after 18 weeks
measure: Objective response rate
timeFrame: At completion of 6 cycles of chemotherapy, which is after 18 weeks.
measure: Overall survival
timeFrame: Determined as the time from randomisation to death from any cause. Average survival rates for this population may be approximately 18 months.
measure: Time to next chemotherapy treatment
timeFrame: Measured from from the date of the last day of trial treatment. approximately after progression which on average would be after 12 months.
measure: Time to response
timeFrame: Determined by time from randomisation to radiological partial response, usually within the 6 cycles of treatment, therefore wihtin 18 weeks.
measure: Quality of life as measured by patients themselves
timeFrame: 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
measure: Number of adverse events and Number of participants with adverse events per arm and the grade of AEs
timeFrame: Form the date of consent to 30 days after trial treatment has stopped.
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial Healthcare NHS Trust
state: Avon
city: Bath
country: United Kingdom
facility: Royal United Hospital
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre, Horfield Road
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: London
country: United Kingdom
facility: Guy's Hospital
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
city: Nottingham
country: United Kingdom
facility: City Hospital, Nottingham
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Taunton
country: United Kingdom
facility: Musgrove Park Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall and Treliske
city: Worcester
country: United Kingdom
facility: Worcestershire Acute Hospitals NHS Trust
Study officials:
affiliation: University Hospitals Bristol and Weston NHS Foundation Trust
name: Amit K Bahl
role: PRINCIPAL_INVESTIGATOR
References: