RECRUITING

A Study of Tucatinib Given Before Surgery to People With HER2+ Cancers That Have Spread to the Brain

Conditions

Metastatic Breast Cancer Tucatinib HER2+Surgery 22-168

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Window of Opportunity Analysis of Pre-Operative Tucatinib for Surgically Resected HER2+ Brain Metastases: Understanding Mechanisms of Resistance

Quick Facts

Study Start:2023-05-09

Study Completion:2028-05-09

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05892068

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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 * 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: 1. Absolute neutrophil count (ANC) ≥1.0 × 103μL, Platelet count ≥75 × 103 /μL, Hemoglobin ≥ 8.0 g/dL 2. 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) 3. Calculated creatinine clearance ≥50 mL/min using the CKD-EPI (2021) (in Cohort A, in patients with elevated serum creatinine, eGFR can be calculated using cystatin C to confirm eligibility) 4. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless on medication known to alter INR and/or aPTT * Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to enrollment and must agree to use adequate contraception prior to enrollment and for the duration of study participation * Patients must be able to swallow and retain oral medication	* 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

Inclusion Criteria

Exclusion Criteria

* 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
* 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:
1. Absolute neutrophil count (ANC) ≥1.0 × 103μL, Platelet count ≥75 × 103 /μL, Hemoglobin ≥ 8.0 g/dL
2. 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)
3. Calculated creatinine clearance ≥50 mL/min using the CKD-EPI (2021) (in Cohort A, in patients with elevated serum creatinine, eGFR can be calculated using cystatin C to confirm eligibility)
4. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless on medication known to alter INR and/or aPTT
* Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to enrollment and must agree to use adequate contraception prior to enrollment and for the duration of study participation
* Patients must be able to swallow and retain oral medication

* 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

Contacts and Locations

Study Contact

Andrew Seidman, MD

CONTACT

646-888-4559

seidmana@mskcc.org

Nelson Moss, MD

CONTACT

212-639-7075

Principal Investigator

Andrew Seidman, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

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

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Andrew Seidman, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-05-09

Study Completion Date2028-05-09

Study Record Updates

Study Start Date2023-05-09

Study Completion Date2028-05-09

Terms related to this study

Keywords Provided by Researchers

Tucatinib
HER2+
Surgery
22-168

Additional Relevant MeSH Terms

Metastatic Breast Cancer