A Study of Tucatinib Given Before Surgery to People With HER2+ Cancers That Have Spread to the Brain
Window of Opportunity Analysis of Pre-Operative Tucatinib for Surgically Resected HER2+ Brain Metastases: Understanding Mechanisms of Resistance
1 other identifier
interventional
9
1 country
7
Brief Summary
The purpose of this study to see how the brain absorbs, distributes, and gets rid of tucatinib in people who have HER2+ cancers (breast cancer, NSCLC, CRC, or GEC) that have spread to the brain, and to learn more about how cancer cells develop resistance to treatment. The researchers will do research tests to look for genetic differences between HER2+ breast cancer that has spread to the brain and progressed during treatment with tucatinib and cancers that are being treated with tucatinib for the first time.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started May 2023
Longer than P75 for phase_2
7 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 9, 2023
CompletedFirst Submitted
Initial submission to the registry
May 18, 2023
CompletedFirst Posted
Study publicly available on registry
June 7, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 9, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 9, 2028
February 13, 2026
February 1, 2026
5 years
May 18, 2023
February 12, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Maximum observed plasma concentration (Cmax) of Tucatinib
by measurement of intrametastasis levels
3 days after treatment
Study Arms (3)
Patients already on Tucatinib
EXPERIMENTALCohort A: This is a non-interventional study patients who will enter while already on Tucatinib . Patients in cohort A who are already on Tucatinib at a dose reduction (i.e., for toxicity) will continue the same dose.
Patients with documented radiological and/or clinical CNS progression with no prior tucatinib
EXPERIMENTALCohort B: Is to administer Tucatinib at standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).
HER2+ esophagogastric, lung, or colon cancer brain metastases and HER2 mutant breast cancer
EXPERIMENTALCohort C: Is to administer Tucatinib at standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).
Interventions
Standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).
Eligibility Criteria
You may qualify if:
- Age ≥18 years with no impairment in decision making capacity
- Patients with HER2 overexpressed/amplified/mutant metastatic breast/lung/esophagogastric/colorectal cancer (IHC, fluorescent in situ hybridation or sequencing-confirmed primary, brain, or other metastatic site) and one or more brain tumor(s) planned for neurosurgical resection. Other untreated brain metastases, and prior radiation (whole brain radiation therapy and/or stereotactic radiosurgery) to the index site are allowed
- Patients with concomitant leptomeningeal disease are eligible provided they have parenchymal brain metastases requiring resection.
- Life expectancy of \>12 weeks.
- ECOG Performance Status (PS) of 0 to 2
- Prior treatments:
- Cohort A: Clinical and or radiological CNS parenchymal progression on tucatinib as most recent line of treatment (tucatinib-resistant) in patients with HER2 overexpressed/amplified breast cancer
- Clinical and or radiological CNS parenchymal progression with no prior tucatinib (tucatinib naïve) in patients with HER2 overexpressed/amplified breast cancer
- Clinical and or radiological CNS parenchymal progression in patients with HER2+/mutant lung/esophagogastric/colorectal cancer and HER2 mutant breast cancer
- ALL PATIENTS:
- Prior conventional dose lapatinib and neratinib are allowed in any cohort if \> 6 months prior
- No limit on prior lines of systemic therapy
- Adequate bone marrow, liver, renal function, and coagulation parameters (obtained ≤ 7 days prior to the first day of study treatment:
- Absolute neutrophil count (ANC) ≥1.0 × 103μL, Platelet count ≥75 × 103 /μL, Hemoglobin ≥ 8.0 g/dL
- Total bilirubin ≤1.5 × upper limit of normal (ULN). Subjects with known history of Gilbert's Syndrome and normal direct bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) are eligible: AST and ALT ≤2.5 × ULN (≤5 × ULN if liver metastases are present)
- +4 more criteria
You may not qualify if:
- Contraindications or history of allergic reaction to tucatinib or any of its excipients
- Significant medical co-morbidities as per investigator evaluation
- Inability to comply with protocol and /or not willing or not available for follow-up assessments or any condition which in the investigator's opinion makes the patient unsuitable for the study participation
- Have used a strong or moderate CYP2C8 inhibitor within 5 half-lives of the inhibitor or have used a strong or moderate CYP2C8 or CYP3A4 inducer within 2 weeks prior to first dose of study treatment (Appendix E)
- Receiving concomitant CYP3A or P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities
- Concurrent pregnancy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Memorial Sloan Kettering Cancer Centerlead
- Pfizercollaborator
- Seagen Inc.collaborator
Study Sites (7)
Memorial Sloan Kettering Cancer Center (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Uniondale, New York, 11553, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Andrew Seidman, MD
Memorial Sloan Kettering Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 18, 2023
First Posted
June 7, 2023
Study Start
May 9, 2023
Primary Completion (Estimated)
May 9, 2028
Study Completion (Estimated)
May 9, 2028
Last Updated
February 13, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.