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Breast CancerPhase 2NCT05748834

Study of Tucatinib and Doxil in Participants With Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Metastatic Breast Cancer

A Phase 2 study testing Tucatinib and Doxil in people with Breast Cancer, run by SCRI Development Innovations, LLC at 8 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This clinical trial is evaluating tucatinib in combination with Doxil in participants with human epidermal growth factor 2 positive (HER2+) locally advanced or metastatic breast cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Tucatinib and Doxil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
8 sitesUnited States
Study dates
24 Jul 2023to Nov 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Written informed consent, according to local guidelines, signed and dated by the patient or by a legal guardian prior to the performance of any study-specific procedures, sampling, or analyses
  • At least 18 years-of-age at the time of signature of the informed consent form (ICF)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
  • Have a confirmed diagnosis of locally advanced/metastatic HER2+ breast cancer (based on local laboratory testing per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines immunohistochemistry 3+ (IHC3+) or fluorescence in situ hybridization + (FISH+))
  • Have had prior treatment with at least 1 line of anti-HER2 therapy for locally advanced/metastatic disease or relapsed within 6 months of completion of adjuvant anti-HER2 therapy. Prior treatment with tucatinib in the metastatic setting is allowed
  • Measurable disease as measured by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
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  • Females of child-bearing potential should be using adequate contraceptive measures from the time of screening until 6 months following the last dose of study drug(s), should not be breast feeding and must have a negative pregnancy test prior to start of dosing, or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
  • Post-menopausal: defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
  • Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not tubal ligation
  • Women under 50 years-of-age will be considered postmenopausal if they have been amenorrheic for at least 12 months following the cessation of exogenous hormonal treatments, and have serum follicle-stimulating hormone and luteinizing hormone levels in the postmenopausal range for the institution.
  • Male patients with female partners of childbearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 6 months following last dose. Male patients must also refrain from donating sperm during their participation in the study.
  • Adequate hematologic function
  • Absolute neutrophil count (ANC) ≥1500/µL
  • Platelet count ≥100,000/µL (no transfusions allowed to meet this requirement)
  • Hemoglobin ≥9 g/dL (at least 2-week washout from any transfusion)
  • Adequate hepatic function
  • Total bilirubin ≤1.5 × upper limit of normal (ULN). Exception: participants with known history of Gilbert's Syndrome who have a direct bilirubin ≤1.5 × ULN in addition to a normal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are eligible.
  • AST and ALT ≤2.5 × ULN (≤5 × ULN if liver metastases are present)
  • Estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73 m2
  • Left ventricular ejection fraction (LVEF) ≥50% based on screening echocardiogram (ECHO)/multigated acquisition (MUGA)
  • Central nervous system (CNS) Inclusion - Based on screening contrast brain magnetic resonance imaging (MRI), patients must have one of the following:
  • No evidence of brain metastases
  • Untreated brain metastases not needing immediate local therapy. For patients with untreated CNS lesions >2.0 cm on screening contrast brain MRI, discussion with and approval from the Medical Monitor is required prior to enrollment.
  • Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions.
  • Previously treated brain metastases:
  • Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy in the opinion of the Investigator.
  • Patients treated with CNS local therapy for newly identified lesions found on contrast brain MRI performed during screening for this study may be eligible to enroll if all of the following criteria are met:
  • Time since whole brain radiotherapy (WBRT) is ≥14 days prior to first dose of treatment, time since stereotactic radiosurgery (SRS) is ≥7 days prior to first dose of treatment, or time since surgical resection is ≥28 days
  • Other sites of disease assessable by RECIST 1.1 are present

Who cannot join

  • Treatment with any of the following:
  • Any systemic anti-cancer chemotherapy or small molecule, biologic, or hormonal agent from a previous treatment regimen or clinical study within 21 days or 5 half-lives (whichever is shorter) prior to the first dose of study drugs. At least 10 days must have elapsed between the last dose of such agent and the first dose of study drugs.
  • Prior treatment with anthracycline in any setting
  • Major surgery (excluding placement of vascular access) within 28 days of first dose of study drugs
  • Palliative radiation therapy within 14 days of first dose of study drugs
  • Based on screening brain MRI, patients must not have any of the following:
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  • Any untreated brain lesions >2.0 cm in size, unless discussed with the Medical Monitor and approval for enrollment is granted
  • Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of >2 mg of dexamethasone (or equivalent). However, patients on a chronic stable dose of ≤2 mg total daily of dexamethasone (or equivalent) may be eligible with discussion and approval by the Medical Monitor
  • Any brain lesion thought to require immediate local therapy, including (but not limited to) a lesion in an anatomic site where increase in size or possible treatment-related edema may pose risk to patient (e.g., brain stem lesions). Patients who undergo local treatment for such lesions identified by screening contrast brain MRI may still be eligible for the study based on criteria described under CNS inclusion criteria 14c
  • Known or suspected leptomeningeal disease (LMD) as documented by the Investigator
  • Have poorly controlled (>1 week) generalized or complex partial seizures, or manifest neurologic progression due to brain metastases, notwithstanding CNS-directed therapy.
  • Use of a strong cytochrome P450 (CYP)2C8-inhibitor or use of a strong CYP3A4 or use of a CYP2C8 inducer within 5 days prior to the first dose of study treatment
  • With the exception of alopecia, any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment. Note: patients with chronic Grade 2 toxicities who are asymptomatic or adequately managed with stable medication may be eligible with approval by the Medical Monitor.
  • Women who are pregnant or nursing or plan to become pregnant while in the study and for at least 6 months after the last administration of study treatment
  • Men who plan to father a child while in the study and for at least 6 months after the last administration of study treatment
  • Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of tucatinib (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2, malabsorption syndrome)
  • Any of the following cardiac criteria:
  • Mean resting QT interval with QT corrected for heart rate by Fridericia's formula [QTcF]) prolongation to >480 msec for females and >460 msec for males in three successive screening measures
  • Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting electrocardiograms (ECGs), e.g., complete left bundle branch block, third-degree heart block
  • Congestive heart failure (New York Heart Association ≥ Grade 2 within past 6 months)
  • Patients with a left ventricular ejection fraction (LVEF) <50% or the lower limit of normal of the institutional standard
  • As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, uncontrolled diabetes mellitus, active bleeding diatheses, or active infection, including hepatitis B and hepatitis C. Screening for chronic conditions is not required.
  • Known human immunodeficiency virus (HIV) infection or positivity on immunoassay. Testing for seropositive status during screening will be at the discretion of the Investigator for subjects without previously reported results.
  • Presence of other active invasive cancers other than the one treated in this study within 3 years prior to screening, except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix, or other local tumors considered cured by local treatment
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol.

Trial locations and contacts

8 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Sarah Cannon Development Innovations contact

1-844-710-6157

SCRI.InnovationsMedical@scri.com

8 sites in 1 country

United States8 sites, 7 recruiting

  • Alliance Cancer Specialists

    Bensalem, Pennsylvania, 19020

    Sramila Aithal, MD

    Recruiting

  • Maryland Oncology Hematology

    Columbia, Maryland, 21044

    Carol Tweed, MD

    Recruiting

  • Texas Oncology- DFW

    Dallas, Texas, 75246

    Joyce O'Shaughnessy, MD

    Recruiting

  • SCRI Oncology Partners

    Nashville, Tennessee, 37203

    Erika Hamilton, MD

    Recruiting

  • Tennessee Oncology

    Nashville, Tennessee, 37203

    Active, not recruiting

  • Virginia Oncology Associates

    Norfolk, Virginia, 23502

    Nino Balanchivadze, MD

    Recruiting

  • Blue Ridge Cancer Care (Oncology & Hematology Assoc of SW Virginia, Inc)

    Salem, Virginia, 24153

    Amanda Gillespie-Twardy, MD

    Recruiting

  • Texas Oncology- San Antonio

    San Antonio, Texas, 78240

    Emmalind Aponte, MD

    Recruiting

Other trials in United States

About this study

Official title: Phase 2 Single Arm Trial With a Safety Lead-in of Tucatinib in Combination With Doxil for the Treatment of HER2+ Metastatic Breast Cancer

This clinical trial is evaluating tucatinib in combination with Doxil in participants with human epidermal growth factor 2 positive (HER2+) locally advanced or metastatic breast cancer. The main goals of this study are to:

  • Learn how well the combination of tucatinib and Doxil works
  • Learn more about the side effects of the combination of tucatinib and Doxil
Read the detailed description

This is a Phase 2, open-label, single-arm study evaluating the combination of tucatinib with Doxil in participants with HER2+ breast cancer who have received at least one prior line of anti-HER2 therapy for locally advanced/metastatic disease or relapsed within 6 months of completion of anti-HER2 adjuvant therapy.

This study will start with a lead-in phase wherein the first 6 patients will be evaluated weekly for one treatment cycle (28 days) to ensure the regimen is safe and tolerable. If no severe and/or unexpected toxicities are observed in these initial patients, the study will continue to enroll a total of 36 patients.

Conditions
Breast Cancer
Being tested
Tucatinib, Doxil
Keywords
Breast Cancer, HER2+, HER2 positive breast cancer, Human epidermal growth factor receptor 2 positive, Doxil, Tucatinib, Tukysa, Anti-HER2, HER2 inhibitor, HER2 blocker, Tyrosine Kinase Inhibitor, Anthracycline
Medical subject headings
Breast Neoplasms

What participants receive

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

  • TucatinibDrug

    Also called Tukysa

    Participants will receive tucatinib 300mg by mouth twice daily continuously (days 1-28) of each 28 day cycle.

  • DoxilDrug

    Also called doxorubicin hydrochloride liposome injection

    Participants will receive Doxil 40mg/m2 intravenously on day 1 of each 28 day cycle (with a maximum cumulative dose of 550mg/m2).

Study groups in NCT05748834
Study groupRoleWhat they receive
Tucatinib Experimental Treatment ArmExperimentalParticipants will receive tucatinib 300mg by mouth twice daily continuously in combination with Doxil 40mg/m2 given intravenously on day 1 of each cycle. Cycles will be 28 days. Up to 36 participants will be enrolled in this Phase 2 study.
Receives: Drug: Tucatinib; Drug: Doxil

What is being measured

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

  1. Objective response rate (ORR) to assess the anti-tumor activity of tucatinib in combination with Doxil using RECIST v1.1.

    Proportion of participants with confirmed complete response (CR) or partial response (PR) to tucatinib in combination with Doxil according to RECIST v1.1 criteria.

    Measured: Up to approximately 40 months.

Secondary outcomes (2)

  1. Number of participants with treatment-related adverse events as assessed by common terminology criteria for adverse events (CTCAE) v5.0.

    Incidence of treatment related adverse events (AEs) using CTCAE v5.0.

    Measured: from informed consent (cycle 0 day -28) to 30 days after the last dose of study treatment. Each cycle is 28 days.

  2. Progression-free survival (PFS) to assess the anti-tumor activity of tucatinib in combination with Doxil using RECIST v1.1.

    Time from the first day of study drug administration (day 1) until disease progression as defined by RECIST v1.1, or death on study.

    Measured: Up to approximately 40 months.

Timeline

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

  1. First posted1 Mar 2023
  2. Study start24 Jul 2023
  3. Primary completionNov 2027 (estimated)
  4. Study completionNov 2027 (estimated)

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05748834
Sponsor's protocol ID
BRE 381
Status last verified
Mar 2026
First submitted
7 Feb 2023
Last updated
20 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tucatinib and Doxil in people with Breast Cancer, run by SCRI Development Innovations, LLC at 8 sites 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 29 inclusion and 25 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: looking for participants now, as of the sponsor's last update on 20 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Contact Sarah Cannon Development Innovations (1-844-710-6157, SCRI.InnovationsMedical@scri.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR) to assess the anti-tumor activity of tucatinib in combination with Doxil using RECIST v1.1. (time frame: Up to approximately 40 months.). 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 NCT05748834.

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 20 Mar 2026.

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