Primary objective:To describe the overall treatment effect of T DXd in HER2+ MBC patients with or without baseline brain metastasisSecondary objectives:- To describe the treatment effect on the development and progression of brain metastasis in…
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Participants without BM at baseline (Cohort 1):
ORR by RECIST 1.1
Participants with BM at baseline (Cohort 2):
PFS by RECIST 1.1
Secondary outcome
For secondary objective 1:
Participants in both cohorts:
OS
DoR
Time to progression
DoT on subsequent lines of therapy
PFS2
Participants without BM at baseline (Cohort 1):
Incidence of new symptomatic CNS metastasis during treatment
In patients who develop isolated CNS progression, receive local therapy, and
continue on protocol therapy:
Time to next progression (CNS or extracranial) or death
Site (CNS vs extracranial vs both) of next progression
For secondary objective 2:
Participants with BM at baseline (Cohort 2):
ORR by RECIST 1.1
CNS PFS (time to CNS progression or death)
Time to new CNS lesions
ORR in brain by RECIST 1.1 as determined by ICR
DoR in brain
For secondary objective 3:
Changes in symptoms, functioning, and HRQoL as measured by
All patients: EORTC QLQ-C30, NANO scale, Cognitive Tests
BM patients: MDASI brain tumor-specific items
ILD/pneumonitis patients: SGRQ-I
For secondary objective 4:
Rate of treatment-related AEs by CTCAE
Rate of investigator-assessed ILD/pneumonitis
* PTs will be matched with most commonly-reported terms within ILD cluster terms
* Rate of ILD clinical symptom resolution among ILD patients who have been
treated with high-dose steroid (total daily dose > 2 mg dexamethasone or
equivalent)
Rate of AEs among patients with baseline BM who are treated with concurrent
high-dose steroid (total daily dose > 2 mg dexamethasone or equivalent)
For secondary objective 5:
Presence of ADAs for T-DXd (confirmatory results: positive or negative, titers)
Background summary
Several agents have been studied in patients with HER2+ breast cancer with
brain metastases. However, due to the decreased quality of life and poor
prognosis in this patient population, there is still a significant unmet need,
particularly for later lines of treatment.
In DESTINY-Breast01, 184 patients with heavily pre-treated breast cancer were
treated with T-DXd at the recommended dose of 5.4 mg/kg. This study population
included 24 patients who had CNS metastases at baseline. Within this small
cohort, the efficacy response for T-DXd was encouraging, supporting a more
extensive evaluation of T DXd in these patients.
The current study is designed to evaluate the efficacy and safety of T-DXd in a
real-world setting. Overall, this study will look to provide a much more robust
and detailed understanding of T DXd that will complement studies that are
ongoing or already completed. This study will be conducted in participants with
advanced, metastatic breast cancer, including participants with
previously-treated, stable BM and participants with active BM, either
previously untreated or progressing (but not requiring immediate local
therapy), to evaluate their response to T-DXd treatment. Therefore, this study
may provide additional treatment options for patients.
Study objective
Primary objective:
To describe the overall treatment effect of T DXd in HER2+ MBC patients with or
without baseline brain metastasis
Secondary objectives:
- To describe the treatment effect on the development and progression of brain
metastasis in patients with or without baseline brain metastasis using
additional efficacy measurements
- To describe efficacy in patients with stable or untreated brain metastasis
(local therapy is allowed for patients with BMs while on study treatment)
- To describe the effect of T-DXd on symptoms, functioning, and HRQoL in HER2+
MBC patients with or without baseline brain metastasis
- To describe the safety profile of T-DXd
- To describe efficacy in patients with or without baseline BM
Study design
Approximately 500 eligible participants will be enrolled. Of these,
approximately 250 eligible participants without BM at baseline (Cohort 1) and
250 eligible participants with BM at baseline (Cohort 2) will be enrolled.
Intervention
All participants will receive IV T-DXd, 5.4 mg/kg, every 3 weeks (21-day
cycle). Participants may continue to receive T-DXd as long as they are
continuing to show clinical benefit, as judged by the investigator, and in the
absence of discontinuation criteria.
After study intervention discontinuation, all participants will undergo an
end-of-treatment visit (within 7 days of discontinuation) and will be followed
up for safety assessments 40 (+ up to 7) days after their last dose of study
intervention (ie, the safety follow-up visit).
Study burden and risks
In general, study participants can experience physical or psychological
discomfort through examination tests and examination
procedures. In addition, subjects can experience side effects from the study
medication.
Storgatan 51
Södertälje 151 36
SE
Storgatan 51
Södertälje 151 36
SE
Listed location countries
Age
Inclusion criteria
Key inclusion Criteria:
1. Pathologically documented breast cancer that:
(a) Is unresectable/advanced or metastatic, and
(b) Has confirmed HER2-positive status as determined according to ASCO/CAP
guidelines (Wolff et al, 2018) evaluated at a local laboratory
2. Participant must have either:
(a) No evidence of BM, or
(b) Untreated BM on screening contrast brain MRI / CT scan
(i)not needing immediate local therapy, or
(ii)For participants with untreated CNS lesions: if lesion <= 2.0 cm no
discussion with study physician is required prior to enrolment, if lesion is
>2.0 cm discussion with and approval from the study physician is required prior
to enrollment, or
(c) Previously treated stable or progressing BM
(i) Previously treated BM with local therapy may either be
radiographically stable for >= 4 weeks since completion of treatment or may
have progressed since prior local CNS therapy, provided that there is no
clinical indication for immediate re-treatment with local therapy
(ii) Patients treated with CNS local therapy for newly identified
lesions found on contrast brain MRI/CT scan performed during screening for
this study who also have other sites of disease assessable by RECIST 1.1
3. Participants with BMs must be neurologically stable and:
(a) Be receiving the equivalent of dexamethasone <= 3 mg/day if treatment is
required
(b) If receiving an anticonvulsant regimen, the regimen must have been
stable for >= 14 days before first day of dosing
(c) Relevant records of any CNS treatment must be available to allow for
classification of TLs and NTLs
4. Previous breast cancer treatment:
(a) Radiologic or objective evidence of disease progression on or after HER2
targeted therapies.
Note: Disease progression within 6 months after adjuvant treatment with HER2
targeted therapies is also acceptable.
(b) No more than 2 lines/regimens of therapy in the metastatic setting.
Note: A line/regimen of treatment should be counted based on a progression
event.
Exclusion criteria
1. Known or suspected LMD 2. Prior exposure to tucatinib treatment 3. Based on
screening contrast brain MRI/ CT scan, participants must not have any of the
following: (a) Any untreated brain lesions > 2.0 cm in size (b) Ongoing use of
systemic corticosteroids for control of symptoms of BMs at a total daily dose
>3 mg of dexamethasone (or equivalent). (c) Any brain lesion thought to require
immediate local therapy, (d) Have poorly controlled (> 1/week) generalized or
complex partial seizures, or manifest neurologic progression due to BMs
notwithstanding CNS-directed therapy 4. Has spinal cord compression
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-005048-46-NL |
| ClinicalTrials.gov | NCT04739761 |
| CCMO | NL77187.068.21 |