Tucatinib, Trastuzumab, and Capecitabine With SRS for Brain Metastases From HER-2 Positive Breast Cancer

Trial Title: Tucatinib, Trastuzumab, and Capecitabine With SRS for Brain Metastases From HER-2 Positive Breast Cancer

NCT ID: NCT05553522

Condition: Brain Metastases
HER2-positive Breast Cancer

Conditions: Official terms:
Breast Neoplasms
Neoplasm Metastasis
Brain Neoplasms
Capecitabine
Trastuzumab
Tucatinib

Conditions: Keywords:
brain metastases
HER2-positive breast cancer

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Combination Product
Intervention name: Combined use of SRS with Tucatinib, Trastuzumab, and Capecitabine
Description: SRS and oral tucatinib for 2 wk, followed by oral tucatinib, oral capecitabine, and intravenous (IV) trastuzumab maintenance during 21-d cycles until tumor progression, participant withdrawal, a severe adverse event deemed related to the study drug, or the treating physician discontinues the drug. There are three dosing levels of tucatinib (Dose Level 0, Dose Level -1, or Dose Level -2) using a dose de-escalation scheme. Dosing of capectabine (1000 mg/m2 BID Days 1-14) and trastuzumab (6 mg/kg once per 21 days; 8 mg/kg initial loading dose) per cycle will remain the same regardless of tucatinib dosing. Dose Level 0: 300 mg twice a day (BID) continuously for 2 wk post SRS, then 300 mg BID continuously per cycle. Dose Level -1: 250 mg twice a day (BID) continuously for 2 wk post SRS, then 250 mg BID continuously per cycle. Dose Level -2: 200 mg twice a day (BID) continuously for 2 wk post SRS, then 200 mg BID continuously per cycle.
Arm group label: Investigational Treatment

Summary: This research study will evaluate how well brain metastases associated with HER-2 positive breast cancer can be controlled using a type of radiation known as stereotactic radiosurgery (SRS) when combined with three therapeutic agents, tucatinib, capecitabine, and trastuzumab. The combined use of SRS with the three drugs is considered investigational.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Histologically confirmed HER-2 -positive breast cancer with newly-diagnosed brain metastases. 2. ECOG Performance Status (PS) of 0, 1, 2 3. Patients with 1-10 brain metastases will be candidates for tucatinib, capecitabine, and trastuzumab with SRS at the discretion of the treating radiation oncologist. Intra-cranial brain metastasis must measure 3 cm or less in the greatest dimension 4. Age 18 years or greater and being willing and able to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures 5. Life expectancy at least 12 weeks 6. Any number of prior systemic therapies will be allowed, except tucatinib and capecitabine. 7. Hemoglobin ≥9g/dL, White blood count ≥3.0 x 10^9/ L , Absolute Granulocyte count ≥1.5x 10^9/ L and platelet count ≥100 × 10^9/ L. 8. Serum bilirubin ≤ 1.5 x ULN 9. AST and / or ALT <= 2 ULN (≤ 5 x ULN when clearly attributable to the presence of liver metastases) 10. Serum creatinine ≤ 1.5 ULN or calculated creatinine clearance > 60ml/min 11. Ability to comply with study procedures and monitoring 12. For women of childbearing potential, a negative pregnancy test should be obtained within one week prior to the start of therapy 13. Male or female patients of reproductive potential need to employ two highly effective and acceptable forms of contraception throughout their participation in the study and for 120 days after last dose of tucatinib, capecitabine and trastuzumab. Highly effective and acceptable forms of contraception are: - Male condom plus spermicide - Cap plus spermicide - Diaphragm plus spermicide - Copper T - Progesterone T - Levonorgestrel-releasing intrauterine system (e.g., Mirena®) - Implants - Hormone shot or injection - Combined pill - Mini-pill - Patch Postmenopausal woman on the study (that will not need contraception) is defined as: - Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments - LH and FSH levels in the postmenopausal range for women under 50 - Radiation-induced oophorectomy with last menses > 1 year ago - Chemotherapy-induced menopause with >1 year interval since last menses - Surgical sterilization (bilateral oophorectomy or hysterectomy). Men and women and members of all races and ethnic groups are eligible for this trial. Exclusion Criteria: 1. Patients with leptomeningeal metastases documented by MRI or CSF evaluation 2. Evidence of intra-tumoral or peri-tumoral hemorrhage deemed significant by the treating physician 3. Brain metastases within 5 mm of the optic chiasm or optic nerve 4. Metastases in the brainstem (midbrain, pons, or medulla) 5. Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom, e.g., Crohn's disease, malabsorption, or CTCAE grade >2 diarrhea of any etiology at baseline 6. History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction, arrhythmia, New York Heart Association (NYHA) functional classification of 3 or 4 7. Unable to undergo brain MRI 8. Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C 9. All toxicities from prior therapies must have resolved to CTCAE v 5.0 grade 1 or better by the time of study enrollment 10. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes, second active malignancy) that could cause unacceptable safety risks or compromise compliance with the protocol 11. Currently receiving other investigational cancer therapy within 4 weeks prior to start of study treatment with the exception of continuing therapy with GnRH analogues 12. Mean QT interval corrected heart rate (QTc) ≥ 470ms calculated from 3 electrocardiograms using Frediricia's Correction 13. Left ventricular ejection fraction (LVEF) <50% 14. Concomitant use of strong cytochrome P450 (CYP)2C8 inhibitor within 5 half-lives of the inhibitor 15. Concomitant use of strong CYP3A4 inducers (e.g. phenytoin, rifampicin, carbamazepine, St. John's Wort) within 5 days prior to the first dose of study treatment 16. Concomitant use of potent CYP2C8 inhibitors within 5 days prior to the first dose of study treatment 17. History of hypersensitivity to tucatinib, capecitabine, and trastuzumab any of its excipients 18. History and/or confirmed corneal ulceration 19. Pregnant or breast feeding

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Miami Cancer Institute at Baptist Health, Inc.

Address:
City: Miami
Zip: 33176
Country: United States

Status: Recruiting

Contact:
Last name: Manmeet Ahluwalia, M.D., MBA

Phone: 786-596-2000
Email: manmeeta@baptisthealth.net

Contact backup:
Last name: Juliana Montoya

Phone: (786) 527-8864
Email: juliana.montoya@baptisthealth.net

Start date: January 29, 2024

Completion date: November 1, 2025

Lead sponsor:
Agency: Baptist Health South Florida
Agency class: Other

Collaborator:
Agency: Seagen Inc.
Agency class: Industry

Source: Baptist Health South Florida

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05553522
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#table3-1)
https://cancer.baptisthealth.net/