Efficacy of cabazitaxel in patients with HER2-negative metastatic breast cancer
- Conditions
- Patients with HER2-negative metastatic breast cancer and having unresectable brain metastases.CancerMalignant neoplasm of breast
- Registration Number
- ISRCTN79877830
- Lead Sponsor
- The Clatterbridge Cancer Centre NHS Foundation Trust (UK)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Female
- Target Recruitment
- 19
First or second line metastatic HER2 negative* breast cancer
1. Oligometastatic brain disease that is unsuitable for surgical resection and/or stereotactic radiosurgery
2. Age 18 years or over
3. ECOG performance status 0-2
4. Diagnosis of metastatic HER2-negative breast cancer
5. At least one measurable target lesion (RECIST 1.0) in the brain** (unsuitable for resection) identified by CT scan or MRI within 21 days of registration.
6. Females of child bearing potential who have a negative pregnancy test prior to study entry
7. Agree to use adequate contraception which they agree to continue for 12 months after the study treatment
8. Ability and capacity to comply with study and follow-up procedure
9. Able to provide written informed consent
*Patients with ER+ve or ER-ve disease are eligible for the study
** Patients with meningeal disease are eligible provided they fit the other criteria. Extracranial disease is not a requirement of this study.
1. Received prior radiotherapy/radiosurgery to the brain (radiotherapy may be offered on disease progression)
2. Received >2 lines of chemotherapy for metastatic recurrent disease (adjuvant treatment is permitted) prior to registration
3. Received any chemotherapy after the diagnosis of brain metastases
4. Previous hormone therapy if it will not be discontinued before Cabazitaxel treatment
5. Patients who have received an increasing dose of steroids to control CNS symptoms within 14 days of registration (steroid use is permitted only when patient is stable at a specific dose at the time of screening)
6. Visceral metastases with no recorded brain metastases
7. Pregnancy or lactation
8. Prior surgery, radiation, chemotherapy, or other anti-cancer therapy within 28 days prior to registration
9. Patients with a history of other previous malignancy except treated CIN or non melanomatous skin cancer
10. Grade =2 peripheral motor and/or sensory neuropathy
11. Grade =2 mucositis oral
12. History of severe hypersensitivity reaction (=grade 3) to taxanes
13. History of severe hypersensitivity reaction (=grade 3) to polysorbate 80-containing drugs
14. Other concurrent serious illness or medical conditions which make it undesirable for the patient to enter the trial (including uncontrolled diabetes mellitus)
15. Inadequate organ and bone marrow function as evidenced by:
15.1. Haemoglobin < 9.0 g/dL
15.2. Absolute neutrophil count < 1.5 x 109/L
15.3. Platelet count <100 x 109/L
15.4. AST/SGOT and/or ALT/SGPT >2.5 x ULN
15.5. total bilirubin >1.0 x ULN
15.6. Serum creatinine >1.5 x ULN. If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated according to CKD-EPI formula and patients with creatinine clearance <60 mL/min should be excluded
16. Active infection requiring systemic antibiotic or anti ? fungal medication.
17. Participation in another clinical trial with any investigational drug within 30 days prior to registration
18. Administration of potent inhibitors and inducers of P450 3A4/5 enzymes within 7 days of registration, or planned concurrent administration whilst on study. This excludes steroid treatment which is standard care treatment for patients with brain metastases
19. Concomitant vaccination with live attenuated vaccines
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall proportion surviving at 18 weeks from registration
- Secondary Outcome Measures
Name Time Method <br> 1. Progression-free survival (PFS) ? defined as the time from registration to the first of one of the following: development of disease progression or death from any cause<br> 2. Overall response for extracranial visceral metastases (ORv) as defined in RECIST 1.0 , recorded from the start of treatment to 18 weeks<br> 3. Overall response for CNS lesions (ORc) defined as a best response of at least PR, recorded from the start of treatment to 18 weeks<br> 4. Acute toxicity (CTCAE v4) after each treatment cycle up to 18 weeks (for the purposes of safety, toxicity will be assessed up until 28 days after the last dose of study treatment)<br> 5. Time to radiotherapy (measured from treatment start date until commencement of radiotherapy)<br> 6. Time to neurological deterioration<br>