TERMINATED

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

Conditions

Brain Metastases HER2-positive Breast Cancer

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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

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.

Official Title

Phase 1 Trial of Tucatinib, Trastuzumab, and Capecitabine With Stereotactic Radiosurgery (SRS) in Patients With Brain Metastases From HER-2 Positive Breast Cancer

Quick Facts

Study Start:2024-01-29

Study Completion:2025-12-17

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:TERMINATED

Study ID

NCT05553522

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:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 × 10\^9/ L , Absolute Granulocyte count ≥1.5x 10\^9/ L and platelet count ≥100 × 10\^9/ L. 8. Serum bilirubin ≤ 1.5 × ULN 9. AST and / or ALT \<= 2 × ULN (≤ 5 × 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 7 months after last dose of tucatinib, capecitabine and trastuzumab. * 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 * 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).	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. 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 5. 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 6. Unable to undergo brain MRI 7. Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C 8. All toxicities from prior therapies must have resolved to CTCAE v 5.0 grade 1 or better by the time of study enrollment 9. 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 10. Currently receiving other investigational cancer therapy within 4 weeks prior to start of study treatment with the exception of continuing therapy with GnRH analogues 11. Mean QT interval corrected heart rate (QTc) ≥ 470ms calculated from 3 electrocardiograms using Frediricia's Correction 12. Left ventricular ejection fraction (LVEF) \<50% 13. Concomitant use of strong cytochrome P450 (CYP)3A inhibitors including macrolide antibiotics (e.g., Telithromycin), antifungals (e.g., Itraconazole), antivirals (e.g., ritonavir), and Nefazodone 14. Concomitant use of strong CYP2C8 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 a strong CYP2C8 inducer within 5 days prior to the first dose of study treatment 17. History of hypersensitivity to tucatinib, capecitabine, and trastuzumab, or any of its excipients 18. History and/or confirmed corneal ulceration 19. Pregnant or breast feeding 20. Use of anthracyline will be prohibited on the protocol

Inclusion Criteria

Exclusion 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 × 10\^9/ L , Absolute Granulocyte count ≥1.5x 10\^9/ L and platelet count ≥100 × 10\^9/ L.
8. Serum bilirubin ≤ 1.5 × ULN
9. AST and / or ALT \<= 2 × ULN (≤ 5 × 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 7 months after last dose of tucatinib, capecitabine and trastuzumab.
* 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
* 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).

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. 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
5. 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
6. Unable to undergo brain MRI
7. Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C
8. All toxicities from prior therapies must have resolved to CTCAE v 5.0 grade 1 or better by the time of study enrollment
9. 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
10. Currently receiving other investigational cancer therapy within 4 weeks prior to start of study treatment with the exception of continuing therapy with GnRH analogues
11. Mean QT interval corrected heart rate (QTc) ≥ 470ms calculated from 3 electrocardiograms using Frediricia's Correction
12. Left ventricular ejection fraction (LVEF) \<50%
13. Concomitant use of strong cytochrome P450 (CYP)3A inhibitors including macrolide antibiotics (e.g., Telithromycin), antifungals (e.g., Itraconazole), antivirals (e.g., ritonavir), and Nefazodone
14. Concomitant use of strong CYP2C8 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 a strong CYP2C8 inducer within 5 days prior to the first dose of study treatment
17. History of hypersensitivity to tucatinib, capecitabine, and trastuzumab, or any of its excipients
18. History and/or confirmed corneal ulceration
19. Pregnant or breast feeding
20. Use of anthracyline will be prohibited on the protocol

Contacts and Locations

Principal Investigator

Manmeet Ahluwalia, M.D., MBA

PRINCIPAL_INVESTIGATOR

Miami Cancer Institute/Baptist Health South Florida

Study Locations (Sites)

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, 33176

United States

Collaborators and Investigators

Sponsor: Baptist Health South Florida

Manmeet Ahluwalia, M.D., MBA, PRINCIPAL_INVESTIGATOR, Miami Cancer Institute/Baptist Health South Florida

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 Date2024-01-29

Study Completion Date2025-12-17

Study Record Updates

Study Start Date2024-01-29

Study Completion Date2025-12-17

Terms related to this study

Keywords Provided by Researchers

brain metastases
HER2-positive breast cancer

Additional Relevant MeSH Terms

Brain Metastases
HER2-positive Breast Cancer