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Evaluation of Neratinib for Treatment and Prevention of Subsequent CNS Event(s) in Patients With Brain Metastasis of Advanced HER2 Positive Breast Cancer

NCT04856475 · Status: WITHDRAWN · Phase: PHASE2 · Type: INTERVENTIONAL

Last updated 2022-03-02

No results posted yet for this study

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.

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).

Conditions

Interventions

DRUG

Neratinib

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)

Sponsors & Collaborators

  • Jules Bordet Institute

    lead OTHER

Principal Investigators

  • Nuria Kotecki, MD · Jules Bordet Institute

Study Design

Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
FEMALE
Healthy Volunteers
No

Timeline & Regulatory

Start
2021-11-24
Primary Completion
2021-11-24
Completion
2021-11-24

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04856475 on ClinicalTrials.gov