Tucatinib treatment before surgery for 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
This study is testing how well the drug tucatinib works in people with HER2+ cancers that have spread to the brain before they have surgery.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 28 (estimated) |
| Ages | 18 Years and up |
| Sex | Female |
| Sponsor | Memorial Sloan Kettering Cancer Center Academic / other |
| Drugs / interventions | tucatinib, lapatinib, neratinib, radiation |
| Locations | 7 sites (Basking Ridge, New Jersey and 6 other locations) |
| Trial ID | NCT05892068 on ClinicalTrials.gov |
What this trial studies
This study investigates how the drug tucatinib is absorbed and processed in patients with HER2+ cancers, specifically those with brain metastases. Participants will take tucatinib orally before undergoing neurosurgery, allowing researchers to analyze tissue and fluid samples to understand the drug's effectiveness and the genetic factors influencing treatment resistance. The study aims to gather insights on both the drug's penetration into brain tumors and the biological response in patients with advanced cancer. Post-surgery treatment will be determined by the treating physician, with some patients potentially continuing tucatinib as part of their care.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 and older with HER2+ metastatic breast cancer and brain tumors requiring surgical intervention.
Not a fit: Patients with non-HER2+ cancers or those without brain metastases may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could improve treatment strategies for patients with HER2+ cancers that have metastasized to the brain.
How similar studies have performed: Other studies have shown promise with tucatinib in treating HER2+ cancers, indicating potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Basking Ridge, New Jersey and 6 other locations
- Memorial Sloan Kettering Cancer Center (Limited Protocol Activities) — Basking Ridge, New Jersey, United States (Recruiting)
- Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States (Recruiting)
- Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale, New Jersey, United States (Recruiting)
- Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities) — Commack, New York, United States (Recruiting)
- Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison, New York, United States (Recruiting)
- Memorial Sloan Kettering Cancer Center — New York, New York, United States (Recruiting)
- Memorial Sloan Kettering Nassau (Limited Protocol Activities) — Uniondale, New York, United States (Recruiting)
Study contacts
- Principal investigator: Andrew Seidman, MD — Memorial Sloan Kettering Cancer Center
- Study coordinator: Andrew Seidman, MD
- Email: seidmana@mskcc.org
- Phone: 646-888-4559
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.