AzTrials
AzTrials

Brain MetastasesPhase 1NCT05553522

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

A Phase 1 study testing Combined use of SRS with Tucatinib, Trastuzumab, and Capecitabine in people with Brain Metastases and HER2-positive Breast Cancer, run by Baptist Health South Florida at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Brain Metastases, HER2-positive Breast Cancer
What is being tested?
Combined use of SRS with Tucatinib, Trastuzumab, and Capecitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
29 Jan 2024to 17 Dec 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed HER-2 -positive breast cancer with newly-diagnosed brain metastases.
  • ECOG Performance Status (PS) of 0, 1, 2
  • 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
  • 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
  • Life expectancy at least 12 weeks
  • Any number of prior systemic therapies will be allowed, except tucatinib and capecitabine.
Show all 32Show fewer
  • 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.
  • Serum bilirubin ≤ 1.5 × ULN
  • AST and / or ALT <= 2 × ULN (≤ 5 × ULN when clearly attributable to the presence of liver metastases)
  • Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance > 60mL/min
  • Ability to comply with study procedures and monitoring
  • For women of childbearing potential, a negative pregnancy test should be obtained within one week prior to the start of therapy
  • 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.

Who cannot join

  • Patients with leptomeningeal metastases documented by MRI or CSF evaluation
  • Evidence of intra-tumoral or peri-tumoral hemorrhage deemed significant by the treating physician
  • Brain metastases within 5 mm of the optic chiasm or optic nerve
  • 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
  • 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
  • Unable to undergo brain MRI
Show all 20Show fewer
  • Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C
  • All toxicities from prior therapies must have resolved to CTCAE v 5.0 grade 1 or better by the time of study enrollment
  • 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
  • Currently receiving other investigational cancer therapy within 4 weeks prior to start of study treatment with the exception of continuing therapy with GnRH analogues
  • Mean QT interval corrected heart rate (QTc) ≥ 470ms calculated from 3 electrocardiograms using Frediricia's Correction
  • Left ventricular ejection fraction (LVEF) <50%
  • 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
  • Concomitant use of strong CYP2C8 inhibitor within 5 half-lives of the inhibitor
  • 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
  • Concomitant use of a strong CYP2C8 inducer within 5 days prior to the first dose of study treatment
  • History of hypersensitivity to tucatinib, capecitabine, and trastuzumab, or any of its excipients
  • History and/or confirmed corneal ulceration
  • Pregnant or breast feeding
  • Use of anthracyline will be prohibited on the protocol

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Miami Cancer Institute at Baptist Health, Inc.

    Miami, Florida, 33176

Other trials in United States

About this study

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

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.

Being tested
Combined use of SRS with Tucatinib, Trastuzumab, and Capecitabine
Keywords
brain metastases, HER2-positive breast cancer
Medical subject headings
Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Combined use of SRS with Tucatinib, Trastuzumab, and CapecitabineCombination product

    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.

Study groups in NCT05553522
Study groupRoleWhat they receive
Investigational TreatmentExperimentalNot described
Receives: Combination Product: Combined use of SRS with Tucatinib, Trastuzumab, and Capecitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose-limiting toxicities (DLTs)

    Toxicities will be graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). DLTs are defined as any of the following events:

    1. Grade 3 or 4 thrombocytopenia
    2. Grade 4 anemia
    3. Grade 4 neutropenia lasting more than 7 days
    4. Febrile neutropenia
    5. Any non-hematologic toxicity of grade 3 or greater (excluding alopecia) despite maximal medical therapy
    6. Grade 4 radiation-induced skin changes
    7. Any episode of noninfectious pneumonitis.

    Measured: During first 4 weeks following SRS

  2. Incidence of radiation-related toxicities

    Toxicities presumed to be due to radiation are defined as:

    1. Acute, < 90 days from treatment start: Expected toxicities include hair loss (for lesions abutting skull), erythema of the scalp (for lesions abutting skull), headache, nausea, and vomiting. Reactions in the ear canals and on the ear should be observed and treated symptomatically. Pin site infection, pin site pain, facial swelling/bruising, and scalp numbness are other common acute effects. Acute toxicity is defined by CTCAE v5.0.
    2. Both acute and delayed, > or = 90 days from treatment start (lethargy, transient worsening of existing neurological deficits) or late (radiation necrosis, cognitive dysfunction, accelerated atherosclerosis, radiation-induced neoplasms) effects of radiotherapy are to be recorded and included in the toxicity evaluation. Late or delayed toxicity is defined by CTCAE v5.0.

    Measured: 30 days of progression or last dose of drug

Secondary outcomes (3)

  1. Progression-free survival (PFS)

    Time from first dose of study drug until the first date of disease progression or death due any cause. The date of disease progression will be defined as the earliest date of disease progression based on central review. For participants whose disease has not progressed at the time of the analysis, censoring will be performed using the date of the last valid disease assessment. The data will be analyzed by the Kaplan-Meier method. PFS will be considered when there is progression just intracranially, as well as when there is progression intracranially or extracranially.

    Measured: Six months

  2. Overall survival

    Time from the beginning of study drug treatment until death due to any cause. For participants who have not died at the time of the analysis, censoring will be performed using the date the patient was last known to be alive. The data will be analyzed by the Kaplan-Meier method.

    Measured: One year

  3. Overall response rate (ORR)

    Proportion of participants with a complete response (CR) or partial response (PR) as defined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. For ORR analysis in all the treated population, participants with an CR or PR will be counted as successes and all other participants (including those with missing response information) will be counted as failures. ORR will be considered for intracranial and extracranial tumors.

    Measured: One year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2022
  2. Study start29 Jan 2024
  3. Primary completion17 Dec 2025
  4. Study completion17 Dec 2025

Why it stopped: Slow enrollment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05553522
Sponsor's protocol ID
2020-AHL-001
Status last verified
Dec 2024
First submitted
16 Sep 2022
Last updated
31 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 25580268

  • 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.

    PubMed 28053022

  • 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.

    PubMed 25015089

  • 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.

    PubMed 17192538

  • 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.

    PubMed 29804905

  • 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.

    PubMed 32468955

  • 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.

    PubMed 27458945

  • 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.

    PubMed 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.

    PubMed 17363516

  • 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.

    PubMed 22203767

  • 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.

    PubMed 21768129

  • 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.

    PubMed 16236738

  • 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.

    PubMed 22149875

  • 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.

    PubMed 10829059

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Combined use of SRS with Tucatinib, Trastuzumab, and Capecitabine in people with Brain Metastases and HER2-positive Breast Cancer, run by Baptist Health South Florida at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 31 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Slow enrollment). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose-limiting toxicities (DLTs) (time frame: During first 4 weeks following SRS). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05553522, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in