Clinical trial NCT04512261: TOPAZ: Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Patients With HER2-Positive Breast Cancer Brain Metastases
Official title: TOPAZ: Single Arm, Open Label Phase 1b/2 Study of Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Patients With HER2-Positive Breast Cancer Brain Metastases
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Brain Metastases
HER2-positive Breast Cancer
CNS Disease
Keywords: tucatinib
pembrolizumab
trastuzumab
Lead sponsor: Cedars-Sinai Medical Center
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: Seagen Inc.
First posted: 2020-08-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single arm, open label trial to assess the safety and efficacy of tucatinib in combination with pembrolizumab and trastuzumab for the treatment of HER2+ breast cancer brain metastases (BCBM). A total of 33 patients with untreated or previously treated and progressing HER2+ BCBM not requiring urgent central nervous system (CNS)-directed therapy will be enrolled. The study will determine the recommended dose of tucatinib in this combination and assess the efficacy of this combination in controlling CNS disease in patients with HER2+ BCBM.


Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years.
2. ECOG performance status of 0-2.
3. HER2+ (as defined by ASCO/CAP clinical practice guideline) metastatic breast cancer.
4. Untreated or previously treated and progressing CNS disease.
5. Measurable CNS metastases.
6. Must be able to undergo MRI of the brain.
7. Adequate organ function.

Exclusion Criteria:

1. Any indication for immediate CNS-directed therapy.
2. History of generalized or complex partial seizures.
3. Any other manifestation of neurologic progression that in the opinion of the treating physician is due to brain metastases.
4. Leptomeningeal disease.
5. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.
6. Prior therapy with tucatinib.
7. Active autoimmune disease that has required systemic treatment in excess of prednisone 10mg daily or equivalent in the past 2 years.

Complete inclusion/exclusion criteria are detailed in the protocol.

Primary outcomes:
measure: 24-week CNS disease control rate (DCR)
timeFrame: 24 weeks
measure: Recommended dose of tucatinib in combination with pembrolizumab and trastuzumab
timeFrame: 24 weeks
Secondary outcomes:
measure: CNS objective response rate (ORR)
timeFrame: From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years.
measure: Systemic ORR
timeFrame: From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years.
measure: Progression-free survival (PFS)
timeFrame: From baseline to first documentation of true progression or symptomatic deterioration, or death due to any cause. Assessed up to 2 years.
measure: Overall Survival (OS)
timeFrame: From baseline until death or 3 years, whichever occurs first.
measure: Toxicity profile of tucatinib, pembrolizumab, and trastuzumab co-administration
timeFrame: From first dose of study treatment until 30 days after the last dose of study treatment.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
Study officials:
affiliation: Cedars-Sinai Medical Center
name: Reva Basho, MD
role: PRINCIPAL_INVESTIGATOR
References: