HER2 Negative Metastatic Breast Cancer
Conditions
Keywords
Breast cancer, HER2 negative, Cabazitaxel, Paclitaxel, Chemotherapy
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.
Interventions
DRUGCabazitaxel
3 weekly cyctotoxic chemotherapy
DRUGPaclitaxel
Weekly cyctotoxic chemotherapy
Sponsors
University Hospitals Bristol and Weston NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Duration of progression free survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate | At the completion of 6 cycles of chemotherapy, which is after 18 weeks | Defined as stable disease rate + partial response rate+complete response rate according to RECIST 1.1 criteria |
| Objective Response Rate | At completion of 6 cycles of chemotherapy, which is after 18 weeks. | 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. |
| Overall Survival | Determined as the time from randomisation to death from any cause. Average survival rates for this population may be approximately 18 months. | Survival duration from randomisation to date of death. |
| Time to Next Chemotherapy Treatment | Measured from from the date of the last day of trial treatment. approximately after progression which on average would be after 12 months. | time from randomisation to another chemotherapy treatment after confirmed progression. |
| Time to Response | 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. | Time taken for tumour burden to respond to treatment |
| Assessment of EQ-5D-5L Questionnaire | 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) | 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. |
| Assessment of EQ-5D-5L VAS Score | 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) | 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. |
| Assessment of FACT-B Questionnaire | 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) | 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. |
Countries
United Kingdom
Contacts
PRINCIPAL_INVESTIGATORAmit K Bahl
University Hospitals Bristol and Weston NHS Foundation Trust
Participant flow
Recruitment details
Patients with HER2 negative metastatic breast cancer were recruited between 2014 and 2020 from NHS Trusts in the UK. First patient randomised December 2014 and last patient randomised March 2020.
Pre-assignment details
None. Screening was as per eligibility criteria
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 58 Years |
| ECOG ECOG 0 | 44 Participants |
| ECOG ECOG 1 | 26 Participants |
| ER status ER negative | 20 Participants |
| ER status ER positive | 117 Participants |
| Presence of liver metastases at baseline No liver mets | 34 Participants |
| Presence of liver metastases at baseline Yes liver mets | 46 Participants |
| Previous docetaxel No previous docetaxel | 98 Participants |
| Previous docetaxel Yes previous docetaxel | 60 Participants |
| Previous treatment with CDK 4/6 iinhibitors No treatment with CDK 4/6 inhibitors | 68 Participants |
| Previous treatment with CDK 4/6 iinhibitors Yes treatment with CDK 4/6 inhibitors | 9 Participants |
| Race and Ethnicity Not Collected | 0 Participants |
| Sex: Female, Male Female | 79 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 69 / 79 | 70 / 79 |
| other Total, other adverse events | 79 / 79 | 79 / 79 |
| serious Total, serious adverse events | 27 / 79 | 24 / 79 |
Outcome results
None listed