Back to resultsTOPAZ: Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Patients With HER2-Positive Breast Cancer Brain Metastases (TOPAZ)
Primary Purpose
Breast Cancer, Brain Metastases, HER2-positive Breast Cancer
Status
Withdrawn
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Tucatinib
Pembrolizumab
Trastuzumab
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring tucatinib, pembrolizumab, trastuzumab
Eligibility Criteria
Inclusion Criteria:
- Age ≥18 years.
- ECOG performance status of 0-2.
- HER2+ (as defined by ASCO/CAP clinical practice guideline) metastatic breast cancer.
- Untreated or previously treated and progressing CNS disease.
- Measurable CNS metastases.
- Must be able to undergo MRI of the brain.
- Adequate organ function.
Exclusion Criteria:
- Any indication for immediate CNS-directed therapy.
- History of generalized or complex partial seizures.
- Any other manifestation of neurologic progression that in the opinion of the treating physician is due to brain metastases.
- Leptomeningeal disease.
- 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.
- Prior therapy with tucatinib.
- 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.
Sites / Locations
- Cedars-Sinai Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tucatinib + Pembrolizumab + Trastuzumab
Arm Description
Patients will receive a combination therapy of tucatinib with pembrolizumab and trastuzumab during the treatment period until progression, treatment intolerance, or patient withdrawal from study. Tucatinib and pembrolizumab are administered as experimental use while trastuzumab is administered per standard use. Patients are expected to be on treatment for at least 12 weeks.
Outcomes
Primary Outcome Measures
24-week CNS disease control rate (DCR)
Percentage of patients who experience objective tumor response [ partial response (PR) or complete response (CR) ] or stable disease as assessed by investigator per RANO-BM reads on protocol-specified MRIs of the brain.
Recommended dose of tucatinib in combination with pembrolizumab and trastuzumab
Secondary Outcome Measures
CNS objective response rate (ORR)
Proportion of participants with confirmed CR or PR per RANO-BM Criteria
Systemic ORR
Proportion of participants with confirmed CR or PR per RECIST v.1.1
Progression-free survival (PFS)
From date of registration to date of first documentation of true progression or symptomatic deterioration (as defined above), or death due to any cause. Patients last known to be alive and progression free are censored at date of last assessment. PFS will be assessed in the CNS and systemically.
Overall Survival (OS)
From date of registration to date of death due to any cause. Patient's last known to be alive are censored at date of last contact.
Toxicity profile of tucatinib, pembrolizumab, and trastuzumab co-administration
Number of adverse events as assessed per CTCAE v.5.
Full Information
NCT ID
NCT04512261
First Posted
July 28, 2020
Last Updated
June 28, 2022
Sponsor
Reva Basho
Collaborators
Merck Sharp & Dohme LLC, Seagen Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04512261
Brief Title
TOPAZ: Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Patients With HER2-Positive Breast Cancer Brain Metastases
Acronym
TOPAZ
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
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Study withdrawn due to change in treatment landscape for HER2+ metastatic breast cancer.
Study Start Date
June 1, 2022 (Anticipated)
Primary Completion Date
June 1, 2024 (Anticipated)
Study Completion Date
June 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Reva Basho
Collaborators
Merck Sharp & Dohme LLC, Seagen Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Brain Metastases, HER2-positive Breast Cancer, CNS Disease
Keywords
tucatinib, pembrolizumab, trastuzumab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tucatinib + Pembrolizumab + Trastuzumab
Arm Type
Experimental
Arm Description
Patients will receive a combination therapy of tucatinib with pembrolizumab and trastuzumab during the treatment period until progression, treatment intolerance, or patient withdrawal from study. Tucatinib and pembrolizumab are administered as experimental use while trastuzumab is administered per standard use. Patients are expected to be on treatment for at least 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Tucatinib
Other Intervention Name(s)
Tukysa
Intervention Description
Initial dosage of trial treatment for tucatinib will be given as 300 mg (dispensed as 2 x 150 mg tablets) orally twice a day for Days 1 - 21 of each 3-week cycle during the treatment period.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
Initial dosage of trial treatment for pembrolizumab will be given as 200 mg by intravenous infusion every 3 weeks on Day 1 of each 3-week cycle during the treatment period. Pembrolizumab will be administered for a maximum of 35 doses.
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Other Intervention Name(s)
Herceptin
Intervention Description
Initial dosage of trial treatment for trastuzumab will be given as 8 mg/kg by intravenous (IV) infusion once on Day 1 of Cycle 1, and 6 mg/kg by IV every 3 weeks on Day 1 of each 3-week cycle starting on Cycle 2 during the treatment period.
Primary Outcome Measure Information:
Title
24-week CNS disease control rate (DCR)
Description
Percentage of patients who experience objective tumor response [ partial response (PR) or complete response (CR) ] or stable disease as assessed by investigator per RANO-BM reads on protocol-specified MRIs of the brain.
Time Frame
24 weeks
Title
Recommended dose of tucatinib in combination with pembrolizumab and trastuzumab
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
CNS objective response rate (ORR)
Description
Proportion of participants with confirmed CR or PR per RANO-BM Criteria
Time Frame
From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years.
Title
Systemic ORR
Description
Proportion of participants with confirmed CR or PR per RECIST v.1.1
Time Frame
From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years.
Title
Progression-free survival (PFS)
Description
From date of registration to date of first documentation of true progression or symptomatic deterioration (as defined above), or death due to any cause. Patients last known to be alive and progression free are censored at date of last assessment. PFS will be assessed in the CNS and systemically.
Time Frame
From baseline to first documentation of true progression or symptomatic deterioration, or death due to any cause. Assessed up to 2 years.
Title
Overall Survival (OS)
Description
From date of registration to date of death due to any cause. Patient's last known to be alive are censored at date of last contact.
Time Frame
From baseline until death or 3 years, whichever occurs first.
Title
Toxicity profile of tucatinib, pembrolizumab, and trastuzumab co-administration
Description
Number of adverse events as assessed per CTCAE v.5.
Time Frame
From first dose of study treatment until 30 days after the last dose of study treatment.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥18 years.
ECOG performance status of 0-2.
HER2+ (as defined by ASCO/CAP clinical practice guideline) metastatic breast cancer.
Untreated or previously treated and progressing CNS disease.
Measurable CNS metastases.
Must be able to undergo MRI of the brain.
Adequate organ function.
Exclusion Criteria:
Any indication for immediate CNS-directed therapy.
History of generalized or complex partial seizures.
Any other manifestation of neurologic progression that in the opinion of the treating physician is due to brain metastases.
Leptomeningeal disease.
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.
Prior therapy with tucatinib.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Reva Basho, MD
Organizational Affiliation
Cedars-Sinai Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
12. IPD Sharing Statement
Learn more about this trial
TOPAZ: Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Patients With HER2-Positive Breast Cancer Brain Metastases
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