Metastatic HER2-positive Breast Cancer With Brain Metastasis Clinical Trial
Official title:
Multicenter, Non-randomised, Open-label, Single Agent Phase II Study to Determine the Clinical Benefit of Trastuzumab Emtansine (T-DM1) in HER2-positive Metastatic Breast Cancer Patients With Brain Metastasis
Women with breast cancer often develop metastases in the brain. Currently, treatment of these metastases is difficult and relies on radiotherapy or surgery which often fail. Therefore, development of new methods of treatment for breast cancer with brain metastasis is very important. T-DM1 is a drug that is already in everyday use for a specific type of breast cancer called HER2-positive breast cancer. The objective of this study is to investigate whether T-DM1 is also effective in brain metastasis and can help patients to live longer and better
This is a multicentre, non-randomised, open label, single arm, phase II study of T-DM1 in
patients with metastatic breast cancer and with brain metastasis who have already failed at
least one line of anti-HER2 therapy for systemic disease. The study sample is composed of 2
distinct cohorts of patients.
Cohort number 1 is composed of patients with asymptomatic or oligosymptomatic brain
metastasis (single or multiple), measurable according to RECIST 1.1, who have not received
any local therapy (neither surgery, radiosurgery nor whole brain radiotherapy) for brain
metastasis.
Cohort number 2 is composed of patients with brain metastasis (single or multiple),
measurable according to RECIST 1.1, previously treated with local therapy (surgery,
radiosurgery or whole brain radiotherapy) and with radiologically confirmed brain
progression, with a minimum period of 3 months between the end of local therapy and brain
progression.
A total number of 110 are planned for screening, in order to enrol 97 patients. A minimum of
87 evaluable patients is necessary. Inclusion of patients in both cohorts will follow a
two-stage Simon optimal design. During the study, both brain assessments via
magnetic-resonance imaging (MRI) and systemic assessments with computerised tomography (CT)
will be performed every 3 cycles (9 weeks) of therapy.
Study treatment consists of T-DM1, 3.6 mg/kg every 3 weeks. Patients will receive study
medication until unacceptable toxicity, voluntary withdrawal from study treatment, disease
progression, death or pregnancy, whichever occurs first. Patients who experience only
progression in the brain and who receive local therapy may remain in the study until systemic
progression (or any of the other reasons stated previously), at the investigator's
discretion.
After the end of study treatment, all patients will have a safety visit within 30 days (+/- 7
days) from the last T-DM1 administration date. After the safety visit, according the reason
of end of study treatment, the follow-up period will begin, as described below:
- If study treatment stopped due to progression of disease Patients will enter directly in
survival follow-up. No visits are mandatory per protocol after the safety visit. Chart
review and/or phone call to check if the patient is still alive are to be performed,
every 6 months, in order to acquire data for the overall survival endpoint. Patients in
survival follow-up who are of childbearing potential must be tested for pregnancy at 3
months and at 7 months after end of study treatment. These tests can be ordered by the
investigator during regular out of study follow-up visits.
- If study treatment stopped for any other reason than progression (either toxicity or
voluntary withdrawal from study treatment) Patients will enter first in efficacy
follow-up after the safety visit and then in survival follow-up when progression disease
is observed.
During efficacy follow-up, 9 weekly efficacy assessments continue according to the same
timetable they would have followed had treatment interruption not occurred. This consists of
imaging assessments (MRI and CT) and medical visits, as well as QoL evaluations. During this
period, treatment is at the discretion of the local physician/investigator.
This follow-up is to continue until disease progression or until voluntary withdrawal of the
patient from the study. In case this follow-up is impossible (due to patient refusing to
perform assessments or other reasons), survival data can be collected every 6 months via
chart review or telephone. Patients in follow-up who are of childbearing potential must be
tested for pregnancy at 3 months and at 7 months after end of study treatment. Once a patient
has progressed while on efficacy follow-up, they will enter into survival follow-up as per
description above.
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