Pilot Study of Cabazitaxel and Paclitaxel in HER2 Negative Breast Cancer (CONCEPT)

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.

Study Overview

• Status: Completed
• Conditions: HER2 Negative Metastatic Breast Cancer
• Intervention / Treatment: Drug: Cabazitaxel; Drug: Paclitaxel

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.

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Bath, United Kingdom
    • Royal United Hospital
  • Blackpool, United Kingdom
    • Blackpool Victoria Hospital
  • Bristol, United Kingdom, BS2 8ED
    • Bristol Haematology and Oncology Centre, Horfield Road
  • Cardiff, United Kingdom
    • Velindre Cancer Centre
  • Exeter, United Kingdom
    • Royal Devon and Exeter Hospital
  • London, United Kingdom
    • Guy's Hospital
  • London, United Kingdom, W6 8RF
    • Imperial Healthcare NHS Trust
  • Newcastle, United Kingdom
    • Freeman Hospital
  • Nottingham, United Kingdom
    • City Hospital, Nottingham
  • Plymouth, United Kingdom
    • Derriford Hospital
  • Taunton, United Kingdom
    • Musgrove Park Hospital
  • Truro, United Kingdom
    • Royal Cornwall and Treliske
  • Worcester, United Kingdom
    • Worcestershire Acute Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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	Objective response rate (ORR) is defined as complete response (CR) plus partial response (PR) as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan every 6 weeks. Tumours were assessed at baseline and compared to the response seen at the completion of treatment. Only responses seen within the 6 cycles of treatment e.g. up to and including the end of treatment tumour assessment are included in this measure. CR - Disappearance of all target lesions; PR >=30% decrease in the sum of the longest diameter of target lesions.	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. This was sometimes seen after treatment end but all responses occurred by 8 months from randomisation therefore within 32 weeks.
Assessment of EQ-5D-5L Questionnaire	EQ-5D-5L will be assessed at baseline, prior to cycle 3 and cycle 5 and at the end of treatment. The patients answer 5 questions which have 5 possible answers from no issue to extreme issue. The answers are given a code, 1, 2, 3, 4 or 5 with 1 for no issue through to 5 for extreme issues which results in a 5 digit 'health state' for that time point. Using a formula this is translated into the 'EQ-5D index value' where 1 is full health and 0 is the worst health. This is what is presented here, the lower the score the worse the quality of life.	EQ5D-5L and FACT B will be completed at baseline, prior to cycle 3 (approximately Day 63), prior to cycle 5 (approximately Day 105) and at the end of treatment visit, (approximately 21 weeks)
Assessment of EQ-5D-5L VAS Score	EQ-5D-5L VAS score was assessed at baseline, prior to cycle 3 and 5 and at the end of treatment. Patients are asked to score their health on a scale 0-100, the higher the score the better they are feeling.	EQ5D-5L and FACT B will be completed at baseline, prior to cycle 3 (approximately Day 63), prior to cycle 5 (approximately Day 105) and at the end of treatment visit, (approximately 21 weeks)
Assessment of FACT-B Questionnaire	FACT-B will be assessed at baseline, prior to cycle 3 and cycle 5 and at the end of treatment. The patients answer 37 questions which have 5 possible answers from not at all to very much. The answers are given a code, 0, 1, 2, 3 or 4 with 0 for not at all through to 4 for very much. The scores are reversed and then totalled to give a value out of 148. This is what is presented here, the higher the score the better the quality of life.	EQ5D-5L and FACT B will be completed at baseline, prior to cycle 3 (approximately Day 63), prior to cycle 5 (approximately Day 105) and at the end of treatment visit, (approximately 21 weeks)

Collaborators and Investigators

• Sponsor: University Hospitals Bristol and Weston NHS Foundation Trust
• Investigators: Principal Investigator: Amit K Bahl, University Hospitals Bristol and Weston NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2014
• Primary Completion (Actual): April 26, 2021
• Study Completion (Actual): March 19, 2025

Study Registration Dates

• First Submitted: October 30, 2014
• First Submitted That Met QC Criteria: February 6, 2017
• First Posted (Estimated): February 9, 2017

Study Record Updates

• Last Update Posted (Actual): July 21, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Breast cancer; HER2 negative; Chemotherapy; Paclitaxel; Cabazitaxel
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Paclitaxel; cabazitaxel
• Other Study ID Numbers: ON/2012/4234

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No