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

Metastatic Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05892068
• Other study ID #: 22-168
• Status: Recruiting
• Phase: Phase 2
• Start date: May 9, 2023
• Est. completion date: May 9, 2028

Study information

• Verified date: April 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Andrew Seidman, MD
• Phone: 646-888-4559
• Email: seidmana[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

All patients will receive tucatinib per-protocol at standard dose of 300 mg orally twice daily on days - 4, -3, -2, -1 and day 0 (in AM). The post-surgery treatment (systemic and/or local) will be decided according to treating physician discretion and is not a study intervention. Tissue samples of brain metastases along with blood/plasma and CSF samples will be analyzed to evaluate brain tumor penetration of tucatinib as well as biologic response to tucatinib in patients with brain metastases from HER2+/mutant breast cancer who are undergoing clinically indicated brain surgery.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: May 9, 2028
• Est. primary completion date: May 9, 2028
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion 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

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:

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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Metastatic Breast Cancer

Intervention

Drug:
• Tucatinib
Standard dose of 300mg orally twice daily for 4 days prior to surgery (day -4 to 0).

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center (Limited Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Seagen Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum observed plasma concentration (Cmax) of Tucatinib	by measurement of intrametastasis levels	3 days after treatment

External Links

•   Memorial Sloan Kettering Cancer Center