Tucatinib, Trastuzumab, and Capecitabine With SRS for Brain Metastases From HER-2 Positive Breast Cancer
NCT ID: NCT05553522
Last Updated: 2025-12-31
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
TERMINATED
PHASE1
1 participants
INTERVENTIONAL
2024-01-29
2025-12-17
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
The combined use of SRS with the three drugs is considered investigational.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Investigational Treatment
Combined use of SRS with Tucatinib, Trastuzumab, and Capecitabine
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Combined use of SRS with Tucatinib, Trastuzumab, and Capecitabine
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.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
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.
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
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
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Pfizer
INDUSTRY
Baptist Health South Florida
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Manmeet Ahluwalia, M.D., MBA
Role: PRINCIPAL_INVESTIGATOR
Miami Cancer Institute/Baptist Health South Florida
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Miami Cancer Institute at Baptist Health, Inc.
Miami, Florida, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Leone JP, Lee AV, Brufsky AM. Prognostic factors and survival of patients with brain metastasis from breast cancer who underwent craniotomy. Cancer Med. 2015 Jul;4(7):989-94. doi: 10.1002/cam4.439. Epub 2015 Mar 9.
Ahluwalia MS, Vogelbaum MV, Chao ST, Mehta MM. Brain metastasis and treatment. F1000Prime Rep. 2014 Dec 1;6:114. doi: 10.12703/P6-114. eCollection 2014.
Moulder SL, Borges VF, Baetz T, Mcspadden T, Fernetich G, Murthy RK, Chavira R, Guthrie K, Barrett E, Chia SK. Phase I Study of ONT-380, a HER2 Inhibitor, in Patients with HER2+-Advanced Solid Tumors, with an Expansion Cohort in HER2+ Metastatic Breast Cancer (MBC). Clin Cancer Res. 2017 Jul 15;23(14):3529-3536. doi: 10.1158/1078-0432.CCR-16-1496. Epub 2017 Jan 4.
Morikawa A, Peereboom DM, Thorsheim HR, Samala R, Balyan R, Murphy CG, Lockman PR, Simmons A, Weil RJ, Tabar V, Steeg PS, Smith QR, Seidman AD. Capecitabine and lapatinib uptake in surgically resected brain metastases from metastatic breast cancer patients: a prospective study. Neuro Oncol. 2015 Feb;17(2):289-95. doi: 10.1093/neuonc/nou141. Epub 2014 Jul 11.
Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. doi: 10.1056/NEJMoa064320.
Pheneger T, Bouhana K, Anderson D, Garrus J, Ahrendt K, Allen S, et al. In Vitro and in vivo activity of ARRY-380: A potent, small molecule inhibitor of ErbB2. AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO. Abstract #1795.
Murthy R, Borges VF, Conlin A, Chaves J, Chamberlain M, Gray T, Vo A, Hamilton E. Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018 Jul;19(7):880-888. doi: 10.1016/S1470-2045(18)30256-0. Epub 2018 May 24.
Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. J Clin Oncol. 2020 Aug 10;38(23):2610-2619. doi: 10.1200/JCO.20.00775. Epub 2020 May 29.
Brown PD, Jaeckle K, Ballman KV, Farace E, Cerhan JH, Anderson SK, Carrero XW, Barker FG 2nd, Deming R, Burri SH, Menard C, Chung C, Stieber VW, Pollock BE, Galanis E, Buckner JC, Asher AL. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA. 2016 Jul 26;316(4):401-409. doi: 10.1001/jama.2016.9839.
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177-82. doi: 10.1126/science.3798106.
Aragon-Ching JB, Zujewski JA. CNS metastasis: an old problem in a new guise. Clin Cancer Res. 2007 Mar 15;13(6):1644-7. doi: 10.1158/1078-0432.CCR-07-0096.
Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, Sneed PK, Chao ST, Weil RJ, Suh J, Bhatt A, Jensen AW, Brown PD, Shih HA, Kirkpatrick J, Gaspar LE, Fiveash JB, Chiang V, Knisely JP, Sperduto CM, Lin N, Mehta M. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol. 2012 Feb 1;30(4):419-25. doi: 10.1200/JCO.2011.38.0527. Epub 2011 Dec 27.
Brufsky AM, Mayer M, Rugo HS, Kaufman PA, Tan-Chiu E, Tripathy D, Tudor IC, Wang LI, Brammer MG, Shing M, Yood MU, Yardley DA. Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clin Cancer Res. 2011 Jul 15;17(14):4834-43. doi: 10.1158/1078-0432.CCR-10-2962.
Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. doi: 10.1056/NEJMoa052122.
Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC, Ross G, Swain SM; CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012 Jan 12;366(2):109-19. doi: 10.1056/NEJMoa1113216. Epub 2011 Dec 7.
Pestalozzi BC, Brignoli S. Trastuzumab in CSF. J Clin Oncol. 2000 Jun;18(11):2349-51. doi: 10.1200/JCO.2000.18.11.2349. No abstract available.
Rusnak DW, Lackey K, Affleck K, Wood ER, Alligood KJ, Rhodes N, Keith BR, Murray DM, Knight WB, Mullin RJ, Gilmer TM. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo. Mol Cancer Ther. 2001 Dec;1(2):85-94.
Sarfraz Z, Ozair A, Bardhan M, Starosciak AK, Perche DC, Hodgson LC, Odia Y, Mehta MP, Kotecha R, McDermott MW, Maharaj A, Leon ACS, Mahtani R, Ahluwalia MS. Tucatinib, trastuzumab, and capecitabine with stereotactic radiosurgery in patients with brain metastases from HER-2 positive breast cancer (TUTOR): Study protocol for a multicenter phase 1 clinical trial. BMC Cancer. 2025 Dec 4. doi: 10.1186/s12885-025-15224-3. Online ahead of print.
Related Links
Access external resources that provide additional context or updates about the study.
FDA Drugs development approval process
Miami Cancer Institute
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2020-AHL-001
Identifier Type: -
Identifier Source: org_study_id