Breast CancerPhase 1/2TOPAZNCT04512261
TOPAZ: Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Patients With HER2-Positive Breast Cancer Brain Metastases
A Phase 1/2 study testing Tucatinib, Pembrolizumab and Trastuzumab in people with Breast Cancer and Brain Metastases, run by Reva Basho at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Brain Metastases, HER2-positive Breast Cancer
- What is being tested?
- Tucatinib, Pembrolizumab and Trastuzumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2022to 1 Jun 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars-Sinai Medical Center
Los Angeles, California, 90048
About this study
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
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.
- Being tested
- Tucatinib, Pembrolizumab, Trastuzumab
- Keywords
- tucatinib, pembrolizumab, trastuzumab
- Medical subject headings
- Breast Neoplasms, Brain Neoplasms, Central Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TucatinibDrug
Also called Tukysa
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.
PembrolizumabDrug
Also called Keytruda
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.
TrastuzumabDrug
Also called Herceptin
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.
| Study group | Role | What they receive |
|---|---|---|
| Tucatinib + Pembrolizumab + Trastuzumab | Experimental | 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. Receives: Drug: Tucatinib; Drug: Pembrolizumab; Drug: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 weeks
Recommended dose of tucatinib in combination with pembrolizumab and trastuzumab
Measured: 24 weeks
Secondary outcomes (5)
CNS objective response rate (ORR)
Proportion of participants with confirmed CR or PR per RANO-BM Criteria
Measured: From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years.
Systemic ORR
Proportion of participants with confirmed CR or PR per RECIST v.1.1
Measured: From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years.
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.
Measured: From baseline to first documentation of true progression or symptomatic deterioration, or death due to any cause. Assessed up to 2 years.
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.
Measured: From baseline until death or 3 years, whichever occurs first.
Toxicity profile of tucatinib, pembrolizumab, and trastuzumab co-administration
Number of adverse events as assessed per CTCAE v.5.
Measured: From first dose of study treatment until 30 days after the last dose of study treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2020
- Study start1 Jun 2022 (estimated)
- Primary completion1 Jun 2024 (estimated)
- Study completion1 Jun 2024 (estimated)
Why it stopped: Study withdrawn due to change in treatment landscape for HER2+ metastatic breast cancer.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Reva Basho
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Seagen Inc.
- Responsible party
- Sponsor-investigator, Reva Basho, Cedars-Sinai Medical Center
- Investigators
- Reva Basho, MD, Principal investigator, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04512261
- Sponsor's protocol ID
- IIT2019-21-Basho-TOPAZ
- Acronym
- TOPAZ
- Status last verified
- Jun 2022
- First submitted
- 28 Jul 2020
- Last updated
- 1 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04512261
- Acronym / sponsor ID
- TOPAZ / IIT2019-21-Basho-TOPAZ
- Keywords
- tucatinib, pembrolizumab, trastuzumab
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study withdrawn due to change in treatment landscape for HER2+ metastatic breast cancer.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Reva BashoUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Seagen Inc.
- Study start
- 1 Jun 2022 (estimated)
- Primary completion
- 1 Jun 2024 (estimated)
- Study completion
- 1 Jun 2024 (estimated)
- First posted
- 13 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tucatinib + Pembrolizumab + Trastuzumab | Experimental | Drug: Tucatinib, Drug: Pembrolizumab, Drug: TrastuzumabPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TucatinibAlso: TukysaInitial 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. | Drug | Tucatinib + Pembrolizumab + Trastuzumab |
| PembrolizumabAlso: KeytrudaInitial 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. | Drug | Tucatinib + Pembrolizumab + Trastuzumab |
| TrastuzumabAlso: HerceptinInitial 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. | Drug | Tucatinib + Pembrolizumab + Trastuzumab |
Primary outcome
24-week CNS disease control rate (DCR)
Time frame: 24 weeks
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
Time frame: 24 weeks
5 secondary outcomes
CNS objective response rate (ORR)
Time frame: From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years.
Systemic ORR
Time frame: From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years.
Progression-free survival (PFS)
Time frame: From baseline to first documentation of true progression or symptomatic deterioration, or death due to any cause. Assessed up to 2 years.
Overall Survival (OS)
Time frame: From baseline until death or 3 years, whichever occurs first.
Toxicity profile of tucatinib, pembrolizumab, and trastuzumab co-administration
Time frame: From first dose of study treatment until 30 days after the last dose of study treatment.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Reva Basho, MD principal investigator
Cedars-Sinai Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tucatinib, Pembrolizumab and Trastuzumab in people with Breast Cancer and Brain Metastases, run by Reva Basho at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 1 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24-week CNS disease control rate (DCR) (time frame: 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2022.