Trial Title:
Study of Tucatinib and Doxil in Participants with Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Metastatic Breast Cancer
NCT ID:
NCT05748834
Condition:
Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Doxorubicin
Liposomal doxorubicin
Tucatinib
Conditions: 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
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Tucatinib
Description:
Participants will receive tucatinib 300mg by mouth twice daily continuously (days 1-28)
of each 28 day cycle.
Arm group label:
Tucatinib Experimental Treatment Arm
Other name:
Tukysa
Intervention type:
Drug
Intervention name:
Doxil
Description:
Participants will receive Doxil 40mg/m2 intravenously on day 1 of each 28 day cycle (with
a maximum cumulative dose of 550mg/m2).
Arm group label:
Tucatinib Experimental Treatment Arm
Other name:
doxorubicin hydrochloride liposome injection
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. 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
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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 longer) 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:
- 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Maryland Oncology Hematology
Address:
City:
Columbia
Zip:
21044
Country:
United States
Status:
Recruiting
Contact:
Last name:
Carol Tweed, MD
Facility:
Name:
SCRI Oncology Partners
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Contact:
Last name:
Erika Hamilton, MD
Facility:
Name:
Tennessee Oncology
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Active, not recruiting
Facility:
Name:
Texas Oncology- DFW
Address:
City:
Dallas
Zip:
75246
Country:
United States
Status:
Recruiting
Contact:
Last name:
Joyce O'Shaughnessy, MD
Facility:
Name:
Texas Oncology- San Antonio
Address:
City:
San Antonio
Zip:
78240
Country:
United States
Status:
Recruiting
Contact:
Last name:
Emmalind Aponte, MD
Facility:
Name:
Virginia Oncology Associates
Address:
City:
Norfolk
Zip:
23502
Country:
United States
Status:
Recruiting
Contact:
Last name:
Nino Balanchivadze, MD
Facility:
Name:
Blue Ridge Cancer Care (Oncology & Hematology Assoc of SW Virginia, Inc)
Address:
City:
Salem
Zip:
24153
Country:
United States
Status:
Recruiting
Contact:
Last name:
Amanda Gillespie-Twardy, MD
Start date:
July 24, 2023
Completion date:
July 2026
Lead sponsor:
Agency:
SCRI Development Innovations, LLC
Agency class:
Other
Collaborator:
Agency:
Seagen Inc.
Agency class:
Industry
Source:
SCRI Development Innovations, LLC
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05748834
