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

Study Purpose

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 HER2+ BCBM not requiring urgent central nervous system (CNS) surgery will be enrolled in this study at Cedars-Sinai Medical Center and MD Anderson Cancer Center to determine the safe recommended dose of tucatinib in this combination. The efficacy of this combination in controlling CNS disease in patients with HER2+ BCBM will be assessed.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender Female
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Women age ≥18 years. 2. ECOG performance status of 0-2. 3. HER2+ metastatic breast cancer as defined byASCO/CAP clinical practice guideline. 4. New untreated CNS disease or CNS disease progression. 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04512261
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Reva Basho
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Reva Basho, MD
Principal Investigator Affiliation Cedars-Sinai Medical Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherIndustryIndustry
Overall Status Not yet recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Breast Cancer, Brain Metastases, HER2-positive Breast Cancer, CNS Disease
Arms & Interventions

Arms

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.

Interventions

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.

Drug: - 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.

Drug: - 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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Cedars-Sinai Medical Center, Los Angeles, California

Status

Address

Cedars-Sinai Medical Center

Los Angeles, California, 90048

Site Contact

Parisa Mirzadehgan, MS, MHDS

Parisa.Mirzadehgan@cshs.org

310-967-4387

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