An open label phase II study to evaluate neratinib for treatment and prevention of subsequent CNS event(s) in patients with brain metastasis of advanced HER2 positive breast cancer
- Conditions
- HER2 positive breast cancer patients with brain metastasesMedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000824-21-BE
- Lead Sponsor
- Institut Jules Bordet
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 125
Subjects must meet all of the following criteria in order to be eligible for this study:
1)Age = 18 years old
2)ECOG performance status = 2
3)Female
4)Diagnosis : histologically or cytologically confirmed HER2-positive tumour status according to the ASCO-CAP guidelines (defined as a 3+ score on immunohistochemistry (IHC) and/or positive by in situ hybridisation (ISH)) with brain metastases, estrogen receptor and progesteron receptor status
Cohort 1: with CNS metastases pre-treated with local approaches for the previous CNS events and currently progressive but locally treated CNS metastasis
Cohort 2: with a first diagnosis of CNS metastases, asymptomatic or paucisymptomatic not needing immediate local therapy
Cohort 3: with confirmed LM defined as the presence of malignant cells in the CSF or combination of typical symptoms and MRI findings
5)Specific criteria for cohorts 1 and 2 only: Must have radiologically confirmed metastatic brain lesion by MRI measurable by RANO-BM criteria
6)Specific criteria for cohort 3 only: LM defined as the presence of malignant cells in the CSF or combination of typical symptoms and MRI findings for cohort 3
7)Subjects should have received at least 1 previous line for the metastatic disease including taxanes based chemotherapy in combination with trastuzumab and pertuzumab (if available) unless contraindicated. Prior tucatinib is not an exclusion criteria.
8)Corticosteroids may be used as long as subjects are on a stable or decreasing dose for at least 7 days prior to study enrolment
9)Serum pregnancy test (for subjects of childbearing potential) negative within 7 days prior to first neratinib administration
10)Women of childbearing potential must agree to use 1 highly effective or 2 effective methods of contraception (as defined at the protocol section 6.8.1) during the course of the study and at least 7 months after the last administration of study treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50
1)CNS disease requiring immediate neurosurgical intervention (e.g. resection, shunt placement, etc.)
2)Any unresolved toxicity = CTCAE grade 2 (except alopecia) from previous anti-cancer therapy
3)Is ineligible for or has already received all chemotherapy options among the physician’s choice
4)Any evidence of severe or uncontrolled systemic disease such as clinically significant cardiovascular, pulmonary, hepatic, renal or metabolic disease
5)Specific criteria for cohort 2 only: Previous local treatment for CNS metastases
6)Specific criteria for cohort 2 only: Oligometastatic disease restricted to the CNS and for which a local treated is considered as the most appropriate treatment by the investigator. 7)Known DPD deficiency* tested by measuring the level of uracil in the blood, or by checking for the presence of certain mutations in the gene for DPD according to EMA recommendation in case investigator’s choice is capecitabine
8)Received an investigational anti-cancer drug within four weeks or five half-lives (whichever is shorter) of study drug administration
9) Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs
10)Known HIV, Hepatitis B or Hepatitis C infection
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method