Her-2 negative breast cancer with brain metastases MedDRA version: 14.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: PT Classification code 10055113 Term: Breast cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Jevtana
Product Name: Cabazitaxel (Jevtana)
Pharmaceutical Form: Concentrate and diluent for solution for infusion
INN or Proposed INN: Cabazitaxel
CAS Number: 183133-96-2
Current Sponsor
Sponsors
The Clatterbridge Cancer Centre NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • First or second line metastatic HER2 negative* breast cancer • Oligometastatic brain disease that is unsuitable for surgical resection and/or stereotactic radiosurgery • Age =18 years • ECOG performance status 0-2 • Diagnosis of metastatic HER2-negative breast cancer • 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. • Females of child bearing potential who have a negative pregnancy test prior to study entry • Agree to use adequate contraception which they agree to continue for 12 months after the study treatment • Ability and capacity to comply with study and follow-up procedure • 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. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 62 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: • Received prior radiotherapy/radiosurgery to the brain (radiotherapy may be offered on disease progression) • Received >2 lines of chemotherapy for metastatic recurrent disease (adjuvant treatment is permitted) prior to registration • Received any chemotherapy after the diagnosis of brain metastases • Previous hormone therapy if it will not be discontinued before Cabazitaxel treatment • 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) • Visceral metastases with no recorded brain metastases • Pregnancy or lactation • Prior surgery, radiation, chemotherapy, or other anti-cancer therapy within 28 days prior to registration • Patients with a history of other previous malignancy except treated CIN or non melanomatous skin cancer • Grade =2 peripheral motor and/or sensory neuropathy • Grade =2 mucositis oral • History of severe hypersensitivity reaction (=grade 3) to taxanes • History of severe hypersensitivity reaction (=grade 3) to polysorbate 80-containing drugs • Other concurrent serious illness or medical conditions which make it undesirable for the patient to enter the trial (including uncontrolled diabetes mellitus) • Inadequate organ and bone marrow function as evidenced by: g. Haemoglobin 2.5 x ULN; k. total bilirubin >1.0 x ULN, l. 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 (18). See Appendix B • Active infection requiring systemic antibiotic or anti – fungal medication. • Participation in another clinical trial with any investigational drug within 30 days prior to registration • 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 • Concomitant vaccination with live attenuated vaccines
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary aim of this study is to determine whether there is evidence for Cabazitaxel increasing 18 week survival from 67% to 81%. Sanofi Ltd. are funding the drug & management costs for this Phase II study. GCSF is being provided by Amgen.This study is designed to assess the feasibility of Cabazitaxel use in breast cancer with brain metastases. Primary outcome: Overall proportion surviving at 18 weeks (i.e. up to 6 cycles of treatment) from registration ;Secondary Objective: Secondary outcomes: • 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) • Overall response for extracranial visceral metastases (ORv) as defined in RECIST 1.0, recorded from the start of treatment to 18 weeks • Overall response for CNS lesions (ORc) defined as a best response of at least PR, recorded from the start of treatment to 18 weeks • 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) • Time to radiotherapy (measured from treatment start date until commencement of radiotherapy) • Time to neurological deterioration ;Primary end point(s): Primary outcome will be Overall response which is defined as a best response of at least PR for CNS lesions, recorded from the start of treatment to completion of 6 cycles of treatment;Timepoint(s) of evaluation of this end point: Overall proportion surviving at 18 weeks (i.e. up to 6 cycles of treatment) from registration | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • 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) • Overall response for extracranial visceral metastases (ORv) as defined in RECIST 1.0, recorded from the start of treatment to 18 weeks • Overall response for CNS lesions (ORc) defined as a best response of at least PR, recorded from the start of treatment to 18 weeks • 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) • Time to radiotherapy (measured from treatment start date until commencement of radiotherapy) • Time to neurological deterioration ;Timepoint(s) of evaluation of this end point: The end of study is defined as 12 months after the last patient’s last dose of study treatment. All patients will be followed up following the end of treatment cycle 6 for as long as possible. | — |
Countries
United Kingdom
Contacts
Public ContactCharlotte Rawcliffe
CRUK Liverpool Cancer Trials Unit
Outcome results
None listed