TOPAZ: Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Patients With HER2-Positive Breast Cancer Brain Metastases

Breast Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04512261
• Other study ID #: IIT2019-21-Basho-TOPAZ
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: June 1, 2022
• Est. completion date: June 1, 2024

Study information

• Verified date: June 2022
• Source: Cedars-Sinai Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 1, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Breast Cancer
• Breast Neoplasms
• Central Nervous System Diseases
• CNS Disease
• HER2-positive Breast Cancer
• Neoplasm Metastasis

Intervention

Drug:
• Tucatinib
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.
• Pembrolizumab
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.
• Trastuzumab
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.

Locations

Country	Name	City	State
United States	Cedars-Sinai Medical Center	Los Angeles	California

Sponsors (3)

Lead Sponsor	Collaborator
Reva Basho	Merck Sharp & Dohme LLC, Seagen Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	24 weeks
Primary	Recommended dose of tucatinib in combination with pembrolizumab and trastuzumab		24 weeks
Secondary	CNS objective response rate (ORR)	Proportion of participants with confirmed CR or PR per RANO-BM Criteria	From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years.
Secondary	Systemic ORR	Proportion of participants with confirmed CR or PR per RECIST v.1.1	From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years.
Secondary	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.	From baseline to first documentation of true progression or symptomatic deterioration, or death due to any cause. Assessed up to 2 years.
Secondary	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.	From baseline until death or 3 years, whichever occurs first.
Secondary	Toxicity profile of tucatinib, pembrolizumab, and trastuzumab co-administration	Number of adverse events as assessed per CTCAE v.5.	From first dose of study treatment until 30 days after the last dose of study treatment.