Breast CancerPhase 2NeraBrainNCT04856475
Evaluation of Neratinib for Treatment and Prevention of Subsequent CNS Event(s) in Patients With Brain Metastasis of Advanced HER2 Positive Breast Cancer
A Phase 2 study testing Neratinib in people with Breast Cancer and Brain Metastases, run by Jules Bordet Institute.
Trial summary
This is an open-label, non-randomised, phase II study to evaluate the efficacy of neratinib in combination with SOC systemic therapy on CNS metastasis both as for secondary prevention (cohort 1), primary treatment (cohort 2) and for the treatment of LM disease (cohort 3) in subjects with HER2 positive metastatic BC. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Brain Metastases
- What is being tested?
- Neratinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 24 Nov 2021to 24 Nov 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years old
- ECOG performance status ≤ 2
- Female
- 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
- Specific criteria for cohorts 1 and 2 only: Must have radiologically confirmed metastatic brain lesion by MRI measurable by RANO-BM criteria
- 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
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- 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.
- Corticosteroids may be used as long as subjects are on a stable or decreasing dose for at least 7 days prior to study enrolment
- Serum pregnancy test (for subjects of childbearing potential) negative within 7 days prior to first neratinib administration
- 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.
- Adequate bone marrow function as defined below:
- Absolute neutrophil count ≥1500/µL or 1.5x109/L
- Hemoglobin ≥ 9 g/dL
- Platelets ≥100000/µL or 100x109/L
- Adequate liver function as defined below:
- Serum total bilirubin ≤ 1.5 x ULN. In case of known Gilbert's syndrome < 3 x ULN is allowed
- AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN (except in case of liver metastases AST/ALT ≤ 5 x ULN)
- Adequate renal function as defined below:
- Creatinine ≤ 1.5 x UNL or creatinine clearance >60 mL/min
- Signed Informed Consent form (ICF) obtained prior to any study related procedure
- LVEF > 55% Inclusion criterion applicable to FRANCE only 1)16) Affiliated to the French Social Security System
Who cannot join
- CNS disease requiring immediate neurosurgical intervention (e.g. resection, shunt placement, etc.)
- Any unresolved toxicity ≥ CTCAE grade 2 (except alopecia) from previous anti-cancer therapy
- Is ineligible for or has already received all chemotherapy options among the physician's choice
- Any evidence of severe or uncontrolled systemic disease such as clinically significant cardiovascular, pulmonary, hepatic, renal or metabolic disease
- Specific criteria for cohort 2 only: Previous local treatment for CNS metastases
- 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.
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- 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
- Received an investigational anti-cancer drug within four weeks or five half-lives (whichever is shorter) of study drug administration
- Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs
- Known HIV, Hepatitis B or Hepatitis C infection
- Pregnant and/or lactating women
- Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study
- Contra-indication for contrast-enhanced MRI (either hypersensitivity to Gd chelate or absolute contra-indication for MRI such as non compatible cardiac stimulator) * Testing of subjects for DPD deficiency in case of capecitabine is proposed according to local practices Exclusion criterion applicable to FRANCE only Vulnerable persons according to the article L.1121-6 of the Public Health Code, adults who are the subject of a measure of legal protection or unable to express their consent according to article L.1121-8 of the Public Health Code
About this study
Official title: 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
This is an open-label, non-randomised, phase II study to evaluate the efficacy of neratinib in combination with SOC systemic therapy on CNS metastasis both as for secondary prevention (cohort 1), primary treatment (cohort 2) and for the treatment of LM disease (cohort 3) in subjects with HER2 positive metastatic BC.
Subjects with metastatic HER2 positive breast cancer will be eligible for the trial and will be enrolled in one of the following cohorts:
Read more
Cohort 1: Eligible subjects include HER2 positive metastatic breast cancer subjects treated with at least one line of systemic anti HER2 therapy and pre-treated with local approaches at least for the previous CNS event and currently progressive but locally treated CNS metastasis. Local therapy includes: stereotactic radiosurgery (SRS) or/and WBRT or/and surgery.
The study will measure the effect of the drug combination on the time to next CNS event(s).
Cohort 2: Eligible subjects include HER2 positive metastatic breast cancer subjects treated with at least one line of systemic anti HER2 therapy or progressing less than 12 months after end of adjuvant therapy with a first diagnosis of brain metastases.
The study will measure the objective CNS response in each subject.
Cohort 3: Eligible subjects include HER2 positive metastatic breast cancer subjects treated with at least one line of systemic anti HER2 therapy with confirmed LM defined as the presence of malignant cells in the cerebrospinal fluid (CSF) or combination of typical symptoms and MRI.
The study will measure the effect of the drug combination on the time to CNS progression including LM progression.
As per investigator's choice, eligible subjects in all cohort will receive neratinib in combination with capecitabine or with T-DM1 or with paclitaxel or with vinorelbine as per investigator's choice. Trastuzumab can be added as per investigator's choice to those regimens except for T-DM1.
At screening and during the study treatment period (every 9 weeks), brain MRI for cohort 1 and cohort 2 or contrast-enhanced neuraxis brain and spine MRI for cohort 3 and tumour assessment by thoracic and abdomino-pelvic CT scan for all cohorts should be performed. For cohort 3 only, CSF cytological assessment should also be performed.
Additionally, at screening and at each cycle during the study treatment period, subjects must fill quality of life questionnaires: EORTC core questionnaire (QLQ-C30) and brain module (QLQ-BN20).
- Conditions
- Breast Cancer, Brain Metastases
- Being tested
- Neratinib
- Medical subject headings
- Breast Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeratinibDrug
As per investigator's choice, eligible subjects in all cohort will receive:
- Neratinib, administered continuously at a dose of 240 mg orally once a day in combination with:
- Capecitabine, administered continuously at a dose of 750 mg/m2, orally, twice a day (=daily dose of 1500 mg/m2) from D1 toD14 (21 days cycle) (preferred option) or
- Vinorelbine, I.V. 25 mg/m2 on D1 and D8 (21 days cycle) or
- Paclitaxel, I.V. 80 mg/m2 on D1, D8, and D15 (21 days cycle) Important note: The possibility to combine trastuzumab, loading dose 8 mg/kg IV followed by 6 mg/kg Q3W IV or SC 600 mg Q3W, to one of these above treatments is left at investigator's discretion OR
- Neratinib, administered continuously at a dose of 160 mg, orally, once a day in combination with:
- T-DM1, I.V. 3.6mg/m2 on D1 (21 days cycle) (preferred option)
| Study group | Role | What they receive |
|---|---|---|
| HER2 metastatic breast cancer locally pretreated for previous CNS events and currently progressive | Experimental | Eligible subjects will receive neratinib in combination with capecitabine or with T-DM1 or with paclitaxel or with vinorelbine as per investigator's choice. Trastuzumab can be added as per investigator's choice to those regimens except for T-DM1.
At screening and during the study treatment period (every 9 weeks), brain MRI and tumour assessment by thoracic and abdomino-pelvic CT scan should be performed. Additionally, at screening and at each cycle during the study treatment period, subjects must fill quality of life questionnaires: EORTC core questionnaire (QLQ-C30) and brain module (QLQ-BN20). Receives: Drug: Neratinib |
| HER2 positive metastatic breast cancer patients with newly diagnosed brain metastases | Experimental | Eligible subjects will receive neratinib in combination with capecitabine or with T-DM1 or with paclitaxel or with vinorelbine as per investigator's choice. Trastuzumab can be added as per investigator's choice to those regimens except for T-DM1.
At screening and during the study treatment period (every 9 weeks), brain MRI and tumour assessment by thoracic and abdomino-pelvic CT scan should be performed. Additionally, at screening and at each cycle during the study treatment period, subjects must fill quality of life questionnaires: EORTC core questionnaire (QLQ-C30) and brain module (QLQ-BN20). Receives: Drug: Neratinib |
| HER2 positive metastatic breast cancer patients with leptomeningeal carcinomatosis | Experimental | Eligible subjects will receive neratinib in combination with capecitabine or with T-DM1 or with paclitaxel or with vinorelbine as per investigator's choice. Trastuzumab can be added as per investigator's choice to those regimens except for T-DM1.
At screening and during the study treatment period (every 9 weeks), contrast-enhanced neuraxis brain and spine MRI and tumour assessment by thoracic and abdomino-pelvic CT scan should be performed. CSF cytological assessment should also be performed.
Additionally, at screening and at each cycle during the study treatment period, subjects must fill quality of life questionnaires: EORTC core questionnaire (QLQ-C30) and brain module (QLQ-BN20). Receives: Drug: Neratinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
For cohort1: Efficacy of neratinib in combination with systemic treatment at investigator's choice in preventing the next CNS event in HER2 breast cancer with known and treated brain metastasis
The efficacy will be assessed by calculating the ratio of the time to the subsequent CNS event (T2) according to RANO-BM criteria to the time between the current CNS event and previous CNS event (T1) both treated locally (T2/T1).
The subsequent CNS event is defined as progression of known and treated brain lesions as well as the development of new brain lesions as assessed on magnetic resonance imaging (MRI) using the RANO-BM criteria.
The time to a subsequent CNS event is defined as the time from treatment start of a CNS event to the occurrence of the following one for both T1 and T2
Measured: From date of enrolment until the date of subsequent documented CNS event, assessed up to 6 months
For cohort 2: Efficacy of neratinib in combination with systemic treatment at investigator's choice on previously untreated brain metastasis from HER2 metastatic breast cancer
The efficacy will be assessed by calculating the proportion of subjects with an objective CNS response, according to RANO-BM criteria in the absence of progressive extra-CNS disease (according to RECIST 1.1).
Measured: From date of enrolment until the date of first documented CNS event, assessed up to 6 months
For cohort 3: Efficacy of neratinib in combination with systemic treatment at investigator's choice on LM disease from HER2 metastatic breast cancer
The efficacy will be assessed by measuring CNS progression-free survival defined as the time between treatment start and date of first leptomeningeal progression (defined according to clinical-neurological or imaging criteria) in the absence of progressive extra-CNS disease (according to RECIST 1.1) or date of death (death from any cause) whatever occurs first.
Measured: From date of enrolment until the date of first documented leptomeningeal progression or date of death from any cause, whichever came first, assessed up to 6 months
Secondary outcomes (15)
Efficacy of neratinib in combination with systemic treatment according to investigator's choice on brain metastasis
Occurrence of new brain metastases according to RECIST 1.1
Measured: From date of enrolment until the date of next documented progression or date of death from any cause, whichever came first, assessed up to 6 months
For cohort 2 only: Evaluation of the time to the first CNS local treatment
Mesure of the time to the first CNS local treatment
Measured: From date of enrolment until the date of first documented CNS event, assessed up to 6 months
Efficacy of neratinib in delaying the time to whole brain radiotherapy (WBRT) in HER2 breast cancer with known brain metastasis (for subject not previously submitted to WBRT)
Mesure of the time to whole brain radiotherapy (WBRT)
Measured: From date of enrolment until the date of next documented progression or date of death from any cause, whichever came first, assessed up to 6 months
Safety of neratinib
Evaluation of the adverse events
Measured: Assessed up to 6 months
Evaluation of the overall survival (OS)
Mesure of the number of overall survival
Measured: up to 2 years
Brain, systemic and bi-comportemental efficacy
Mesure of Clinical Benefit (CB) according to RANO-BM criteria and RECIST 1.1
Measured: Through study completion, up to 2 years
Brain, systemic and bi-comportemental efficacy
Mesure of Objective Response Rate (ORR) - including intracranial ORR according to RANO-BM criteria and RECIST 1.1
Measured: Through study completion, up to 2 years
Brain, systemic and bi-comportemental efficacy
Mesure of Best Response (BR) according to RANO-BM criteria and RECIST 1.1
Measured: Through study completion, up to 2 years
Brain, systemic and bi-comportemental efficacy
Mesure of CNS Progression-Free survival according to RANO-BM criteria and RECIST 1.1
Measured: Through study completion, up to 2 years
Brain, systemic and bi-comportemental efficacy
Mesure of Extra CNS Progression-Free survival. Assessment of extra-CNS lesions will use the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measured: Through study completion, up to 2 years
Brain, systemic and bi-comportemental efficacy
Mesure of overall Progression-Free Survival (PFS) according to RANO-BM criteria and RECIST 1.1
Measured: Through study completion, up to 2 years
Brain, systemic and bi-comportemental efficacy
Mesure of Duration of Response (DoR) according to RANO-BM criteria and RECIST 1.1
Measured: Through study completion, up to 2 years
Brain, systemic and bi-comportemental efficacy
Mesure of Duration of Clinical Benefit (DCB) according to RANO-BM criteria and RECIST 1.1
Measured: Through study completion, up to 2 years
Assessment of the quality of life
Analysis of Quality of life questionnaire "EORTC QLQ-C30"
Measured: Assessed up to 6 months
Assessment of the quality of life
Analysis of Quality of life questionnaire "Brain module QLQ-BN20"
Measured: Assessed up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2021
- Study start24 Nov 2021
- Primary completion24 Nov 2021
- Study completion24 Nov 2021
Why it stopped: Termination of collaboration with PUMA
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This is an open-label, non-randomised, phase II study to evaluate the efficacy of neratinib in combination with SOC systemic therapy on CNS metastasis both as for secondary prevention (cohort 1), primary treatment (cohort 2) and for the treatment of LM disease (cohort 3) in subjects with HER2 positive metastatic BC.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jules Bordet Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nuria Kotecki, MD, Study chair, Jules Bordet Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04856475
- Sponsor's protocol ID
- IJB-NERABRAIN-ODN-007
- Acronym
- NeraBrain
- Status last verified
- Jun 2021
- First submitted
- 30 Mar 2021
- Last updated
- 2 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04856475
- Acronym / sponsor ID
- NeraBrain / IJB-NERABRAIN-ODN-007
- Conditions
- Breast Cancer, Brain Metastases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Termination of collaboration with PUMA
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Jules Bordet InstituteUniversity, hospital or other
- Study start
- 24 Nov 2021 (actual)
- Primary completion
- 24 Nov 2021 (actual)
- Study completion
- 24 Nov 2021 (actual)
- First posted
- 23 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open-label, non-randomised, phase II study to evaluate the efficacy of neratinib in combination with SOC systemic therapy on CNS metastasis both as for secondary prevention (cohort 1), primary treatment (cohort 2) and for the treatment of LM disease (cohort 3) in subjects with HER2 positive metastatic BC.
Subjects with metastatic HER2 positive breast cancer will be eligible for the trial and will be enrolled in one of the following cohorts:
Cohort 1: Eligible subjects include HER2 positive metastatic breast cancer subjects treated with at least one line of systemic anti HER2 therapy and pre-treated with local approaches at least for the previous CNS event and currently progressive but locally treated CNS metastasis. Local therapy includes: stereotactic radiosurgery (SRS) or/and WBRT or/and surgery.
The study will measure the effect of the drug combination on the time to next CNS event(s).
Cohort 2: Eligible subjects include HER2 positive metastatic breast cancer subjects treated with at least one line of systemic anti HER2 therapy or progressing less than 12 months after end of adjuvant therapy with a first diagnosis of brain metastases.
The study will measure the objective CNS response in each subject.
Cohort 3: Eligible subjects include HER2 positive metastatic breast cancer subjects treated with at least one line of systemic anti HER2 therapy with confirmed LM defined as the presence of malignant cells in the cerebrospinal fluid (CSF) or combination of typical symptoms and MRI.
The study will measure the effect of the drug combination on the time to CNS progression including LM progression.
As per investigator's choice, eligible subjects in all cohort will receive neratinib in combination with capecitabine or with T-DM1 or with paclitaxel or with vinorelbine as per investigator's choice. Trastuzumab can be added as per investigator's choice to those regimens except for T-DM1.
At screening and during the study treatment period (every 9 weeks), brain MRI for cohort 1 and cohort 2 or contrast-enhanced neuraxis brain and spine MRI for cohort 3 and tumour assessment by thoracic and abdomino-pelvic CT scan for all cohorts should be performed. For cohort 3 only, CSF cytological assessment should also be performed.
Additionally, at screening and at each cycle during the study treatment period, subjects must fill quality of life questionnaires: EORTC core questionnaire (QLQ-C30) and brain module (QLQ-BN20).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This is an open-label, non-randomised, phase II study to evaluate the efficacy of neratinib in combination with SOC systemic therapy on CNS metastasis both as for secondary prevention (cohort 1), primary treatment (cohort 2) and for the treatment of LM disease (cohort 3) in subjects with HER2 positive metastatic BC.
| Arm | Type | Receives |
|---|---|---|
| HER2 metastatic breast cancer locally pretreated for previous CNS events and currently progressive | Experimental | Drug: NeratinibEligible subjects will receive neratinib in combination with capecitabine or with T-DM1 or with paclitaxel or with vinorelbine as per investigator's choice. Trastuzumab can be added as per investigator's choice to those regimens except for T-DM1. At screening and during the study treatment period (every 9 weeks), brain MRI and tumour assessment by thoracic and abdomino-pelvic CT scan should be performed. Additionally, at screening and at each cycle during the study treatment period, subjects must fill quality of life questionnaires: EORTC core questionnaire (QLQ-C30) and brain module (QLQ-BN20). |
| HER2 positive metastatic breast cancer patients with newly diagnosed brain metastases | Experimental | Drug: NeratinibEligible subjects will receive neratinib in combination with capecitabine or with T-DM1 or with paclitaxel or with vinorelbine as per investigator's choice. Trastuzumab can be added as per investigator's choice to those regimens except for T-DM1. At screening and during the study treatment period (every 9 weeks), brain MRI and tumour assessment by thoracic and abdomino-pelvic CT scan should be performed. Additionally, at screening and at each cycle during the study treatment period, subjects must fill quality of life questionnaires: EORTC core questionnaire (QLQ-C30) and brain module (QLQ-BN20). |
| HER2 positive metastatic breast cancer patients with leptomeningeal carcinomatosis | Experimental | Drug: NeratinibEligible subjects will receive neratinib in combination with capecitabine or with T-DM1 or with paclitaxel or with vinorelbine as per investigator's choice. Trastuzumab can be added as per investigator's choice to those regimens except for T-DM1. At screening and during the study treatment period (every 9 weeks), contrast-enhanced neuraxis brain and spine MRI and tumour assessment by thoracic and abdomino-pelvic CT scan should be performed. CSF cytological assessment should also be performed. Additionally, at screening and at each cycle during the study treatment period, subjects must fill quality of life questionnaires: EORTC core questionnaire (QLQ-C30) and brain module (QLQ-BN20). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Age ≥ 18 years old
- ECOG performance status ≤ 2
- Female
- 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
- Specific criteria for cohorts 1 and 2 only: Must have radiologically confirmed metastatic brain lesion by MRI measurable by RANO-BM criteria
Key exclusion criteria (13 listed)
- CNS disease requiring immediate neurosurgical intervention (e.g. resection, shunt placement, etc.)
- Any unresolved toxicity ≥ CTCAE grade 2 (except alopecia) from previous anti-cancer therapy
- Is ineligible for or has already received all chemotherapy options among the physician's choice
- Any evidence of severe or uncontrolled systemic disease such as clinically significant cardiovascular, pulmonary, hepatic, renal or metabolic disease
- Specific criteria for cohort 2 only: Previous local treatment for CNS metastases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NeratinibAs per investigator's choice, eligible subjects in all cohort will receive: * Neratinib, administered continuously at a dose of 240 mg orally once a day in combination with: * Capecitabine, administered continuously at a dose of 750 mg/m2, orally, twice a day (=daily dose of 1500 mg/m2) from D1 toD14 (21 days cycle) (preferred option) or * Vinorelbine, I.V. 25 mg/m2 on D1 and D8 (21 days cycle) or * Paclitaxel, I.V. 80 mg/m2 on D1, D8, and D15 (21 days cycle) Important note: The possibility to combine trastuzumab, loading dose 8 mg/kg IV followed by 6 mg/kg Q3W IV or SC 600 mg Q3W, to one of these above treatments is left at investigator's discretion OR * Neratinib, administered continuously at a dose of 160 mg, orally, once a day in combination with: * T-DM1, I.V. 3.6mg/m2 on D1 (21 days cycle) (preferred option) | Drug | HER2 metastatic breast cancer locally pretreated for previous CNS events and currently progressive, HER2 positive metastatic breast cancer patients with leptomeningeal carcinomatosis, HER2 positive metastatic breast cancer patients with newly diagnosed brain metastases |
Primary outcome
For cohort1: Efficacy of neratinib in combination with systemic treatment at investigator's choice in preventing the next CNS event in HER2 breast cancer with known and treated brain metastasis
Time frame: From date of enrolment until the date of subsequent documented CNS event, assessed up to 6 months
The efficacy will be assessed by calculating the ratio of the time to the subsequent CNS event (T2) according to RANO-BM criteria to the time between the current CNS event and previous CNS event (T1) both treated locally (T2/T1). The subsequent CNS event is defined as progression of known and treated brain lesions as well as the development of new brain lesions as assessed on magnetic resonance imaging (MRI) using the RANO-BM criteria. The time to a subsequent CNS event is defined as the time from treatment start of a CNS event to the occurrence of the following one for both T1 and T2
For cohort 2: Efficacy of neratinib in combination with systemic treatment at investigator's choice on previously untreated brain metastasis from HER2 metastatic breast cancer
Time frame: From date of enrolment until the date of first documented CNS event, assessed up to 6 months
The efficacy will be assessed by calculating the proportion of subjects with an objective CNS response, according to RANO-BM criteria in the absence of progressive extra-CNS disease (according to RECIST 1.1).
For cohort 3: Efficacy of neratinib in combination with systemic treatment at investigator's choice on LM disease from HER2 metastatic breast cancer
Time frame: From date of enrolment until the date of first documented leptomeningeal progression or date of death from any cause, whichever came first, assessed up to 6 months
The efficacy will be assessed by measuring CNS progression-free survival defined as the time between treatment start and date of first leptomeningeal progression (defined according to clinical-neurological or imaging criteria) in the absence of progressive extra-CNS disease (according to RECIST 1.1) or date of death (death from any cause) whatever occurs first.
15 secondary outcomes
Efficacy of neratinib in combination with systemic treatment according to investigator's choice on brain metastasis
Time frame: From date of enrolment until the date of next documented progression or date of death from any cause, whichever came first, assessed up to 6 months
For cohort 2 only: Evaluation of the time to the first CNS local treatment
Time frame: From date of enrolment until the date of first documented CNS event, assessed up to 6 months
Efficacy of neratinib in delaying the time to whole brain radiotherapy (WBRT) in HER2 breast cancer with known brain metastasis (for subject not previously submitted to WBRT)
Time frame: From date of enrolment until the date of next documented progression or date of death from any cause, whichever came first, assessed up to 6 months
Safety of neratinib
Time frame: Assessed up to 6 months
Evaluation of the overall survival (OS)
Time frame: up to 2 years
Brain, systemic and bi-comportemental efficacy
Time frame: Through study completion, up to 2 years
Brain, systemic and bi-comportemental efficacy
Time frame: Through study completion, up to 2 years
Brain, systemic and bi-comportemental efficacy
Time frame: Through study completion, up to 2 years
Brain, systemic and bi-comportemental efficacy
Time frame: Through study completion, up to 2 years
Brain, systemic and bi-comportemental efficacy
Time frame: Through study completion, up to 2 years
Brain, systemic and bi-comportemental efficacy
Time frame: Through study completion, up to 2 years
Brain, systemic and bi-comportemental efficacy
Time frame: Through study completion, up to 2 years
Brain, systemic and bi-comportemental efficacy
Time frame: Through study completion, up to 2 years
Assessment of the quality of life
Time frame: Assessed up to 6 months
Assessment of the quality of life
Time frame: Assessed up to 6 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2022.
- Individual participant dataSharing planned: Undecided
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Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nuria Kotecki, MD study chair
Jules Bordet Institute
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Neratinib in people with Breast Cancer and Brain Metastases, run by Jules Bordet Institute.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 2 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
For cohort1: Efficacy of neratinib in combination with systemic treatment at investigator's choice in preventing the next CNS event in HER2 breast cancer with known and treated brain metastasis (time frame: From date of enrolment until the date of subsequent documented CNS event, assessed up to 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2022.