TOPAZ: Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Women With HER2-Positive Breast Cancer Brain Metastases (TOPAZ)
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|ClinicalTrials.gov Identifier: NCT04512261|
Recruitment Status : Not yet recruiting
First Posted : August 13, 2020
Last Update Posted : August 13, 2020
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer Brain Metastases HER2-positive Breast Cancer CNS Disease||Drug: Tucatinib Drug: Pembrolizumab Drug: Trastuzumab||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||33 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||TOPAZ: Single Arm, Open Label Phase 1b/2 Study of Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Women With HER2-Positive Breast Cancer Brain Metastases|
|Estimated Study Start Date :||October 1, 2020|
|Estimated Primary Completion Date :||April 1, 2023|
|Estimated Study Completion Date :||April 1, 2023|
Experimental: Tucatinib + Pembrolizumab + Trastuzumab
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.
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.
Other Name: Tukysa
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.
Other Name: Keytruda
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.
Other Name: Herceptin
- 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 ]
- CNS objective response rate (ORR) [ Time Frame: From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years. ]Proportion of participants with confirmed CR or PR per RANO-BM Criteria
- Systemic ORR [ Time Frame: From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years. ]Proportion of participants with confirmed CR or PR per RECIST v.1.1
- 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. ]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) [ Time Frame: From baseline until death or 3 years, whichever occurs first. ]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 [ Time Frame: From first dose of study treatment until 30 days after the last dose of study treatment. ]Number of adverse events as assessed per CTCAE v.5.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04512261
|Contact: Parisa Mirzadehgan, MPH, MHDS||310-967-4387||Parisa.Mirzadehgan@cshs.org|
|United States, California|
|Cedars-Sinai Medical Center|
|Los Angeles, California, United States, 90048|
|Contact: Parisa Mirzadehgan, MS, MHDS 310-967-4387 Parisa.Mirzadehgan@cshs.org|
|Principal Investigator: Reva Basho, MD|
|Sub-Investigator: Heather McArthur, MD, MPH|
|Sub-Investigator: Alain Mita, MD|
|Sub-Investigator: Philomena McAndrew, MD|
|Sub-Investigator: Dorothy Park, MD|
|Sub-Investigator: Mary El-Masry, MD|
|Sub-Investigator: Jethro Hu, MD|
|Sub-Investigator: Surasak Phuphanich, MD|
|Sub-Investigator: Jeremy Rudnick, MD|
|Sub-Investigator: Stephen Shiao, MD|
|Sub-Investigator: Michele Burnison, MD|
|Sub-Investigator: Amin Mirhadi, MD|
|Principal Investigator:||Reva Basho, MD||Cedars-Sinai Medical Center|