Trial Title:
Tamoxifen and Pegylated Liposomal Doxorubicin for the Treatment of Patients With Metastatic or Inoperable, Locally Advanced Triple Negative Breast Cancer
NCT ID:
NCT06434064
Condition:
Anatomic Stage III Breast Cancer AJCC v8
Anatomic Stage IV Breast Cancer AJCC v8
Locally Advanced Unresectable Triple-Negative Breast Carcinoma
Metastatic Triple-Negative Breast Carcinoma
Conditions: Official terms:
Carcinoma
Breast Neoplasms
Triple Negative Breast Neoplasms
Tamoxifen
Doxorubicin
Liposomal doxorubicin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo tumor biopsy
Arm group label:
Treatment (tamoxifen, pegylated liposomal doxorubicin)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (tamoxifen, pegylated liposomal doxorubicin)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Treatment (tamoxifen, pegylated liposomal doxorubicin)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo echocardiography
Arm group label:
Treatment (tamoxifen, pegylated liposomal doxorubicin)
Other name:
EC
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (tamoxifen, pegylated liposomal doxorubicin)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Drug
Intervention name:
Pegylated Liposomal Doxorubicin Hydrochloride
Description:
Given IV
Arm group label:
Treatment (tamoxifen, pegylated liposomal doxorubicin)
Other name:
ATI-0918
Other name:
Caelyx
Other name:
Dox-SL
Other name:
Doxil
Other name:
Doxilen
Other name:
Doxorubicin HCl Liposomal
Other name:
Doxorubicin HCl Liposome
Other name:
Doxorubicin Hydrochloride Liposome
Other name:
Duomeisu
Other name:
Evacet
Other name:
LipoDox
Other name:
Lipodox 50
Other name:
Liposomal Adriamycin
Other name:
Liposomal Doxorubicin Hydrochloride
Other name:
Liposomal-Encapsulated Doxorubicin
Other name:
Pegylated Doxorubicin HCl Liposome
Other name:
Pegylated Liposomal Doxorubicin
Other name:
S-Liposomal Doxorubicin
Other name:
Stealth Liposomal Doxorubicin
Other name:
TLC D-99
Intervention type:
Drug
Intervention name:
Tamoxifen
Description:
Given PO
Arm group label:
Treatment (tamoxifen, pegylated liposomal doxorubicin)
Other name:
TMX
Summary:
This phase II trial tests how well tamoxifen and pegylated liposomal doxorubicin works in
treating patients with triple negative breast cancer that has spread from where it first
started (primary site) to other places in the body (metastatic) or that has spread to
nearby tissue or lymph nodes (locally advanced) and is unable to be operated on
(inoperable). Tamoxifen works by blocking the effects of estrogen in the breast. This may
help stop the growth of tumor cells that need estrogen to grow. Doxorubicin is in a class
of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill
cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair.
Liposomal doxorubicin is a form of the anticancer drug doxorubicin that is contained
inside very tiny, fat-like particles. Liposomal doxorubicin may have fewer side effects
and work better than other forms of the drug. Giving tamoxifen and pegylated liposomal
doxorubicin together may work better in treating patients with metastatic or inoperable,
locally advanced triple negative breast cancer than giving either of these drugs alone.
Detailed description:
PRIMARY OBJECTIVE:
I. To determine the efficacy of the combination of tamoxifen and pegylated liposomal
doxorubicin in patients with metastatic or inoperable locally advanced triple negative
breast cancer (TNBC) (estrogen receptor [ER] < 10%) as assessed by overall response rate
(ORR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)
1.1.
SECONDARY OBJECTIVES:
I. To assess the safety and tolerability of pegylated liposomal doxorubicin given in
combination with tamoxifen.
II. To determine clinical benefit including overall and progression free survival
(overall survival [OS] and progression free survival [PFS]) as defined by RECIST v1.1.
III. To determine the duration of response.
EXPLORATORY OBJECTIVES:
I. To analyze changes in circulating tumor deoxyribonucleic acid (ctDNA) from
longitudinal liquid biopsy to follow therapeutic response.
II. To determine estrogen receptor beta (ERβ)-mutant p53 interaction in tumors with in
situ proximity ligation assay (PLA).
III. To analyze changes in gene expression by global ribonucleic acid (RNA)-sequencing
(seq).
IV. To determine changes in the tumor microenvironment (TME) of tumors in response to
treatment by analyzing tumor infiltrating lymphocytes (TILS) selected markers in the
tumor and stromal tissues combined with CYBERSORT analysis of the transcriptome data.
V. Analyze changes in immune cell populations and circulating protein biomarkers as
detectable from blood.
OUTLINE:
Patients receive tamoxifen orally (PO) once daily (QD) on days 1-28 of each cycle and
pegylated liposomal doxorubicin intravenously (IV) on day 1 of each cycle. Cycles repeat
every 28 days in the absence of disease progression or unacceptable toxicity. Patients
undergo echocardiography, computed tomography (CT) scan or magnetic resonance imaging
(MRI), tumor biopsy and blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 30 days and every 6
months for up to 2 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients with pathologically confirmed metastatic triple negative breast cancer (ER
≤ 10%) that have been previously treated with at least 2 lines of therapy in the
metastatic setting
- Patients must have ERα (estrogen receptor alpha) and PgR (progesterone receptor)
status assessed using current American Society of Clinical Oncology (ASCO) College
of American Pathologists (CAP) guidelines. Patients are eligible if the tumor
staining is ERα low/negative (ER ≤ 10%) and PgR negative by ASCO/CAP guidelines
- The tumor must be HER-2 negative by immunochemistry (IHC) 0-1+ or IHC 2 + and
fluorescence in situ hybridization (FISH) negative
- Patients must be ≥ 18 years of age
- Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance
status of 0-1
- Absolute neutrophil count (ANC) ≥ 1500/ μL
- Hemoglobulin (hb) ≥ 9 g/dL
- Platelet count ≥ 100,000/ μL
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2 x ULN
- Creatinine clearance > 60 mL/min (Cockroft-Gault Equation)
- Left ventricular ejection fraction (LVEF) assessment must be performed within 30
days prior to enrollment. (LVEF assessment performed by 2-D echocardiogram is
preferred; however, multigated acquisition scan [MUGA] scan may be substituted based
on institutional preferences). The LVEF must be ≥ 50% regardless of the cardiac
imaging facility's lower limit of normal
- Patients must be able to swallow oral medications
- Participants of child-bearing potential must agree to use adequate contraceptive
methods (e.g., hormonal or barrier method of birth control; abstinence) prior to
study entry. Should a woman become pregnant or suspect she is pregnant while she or
her partner is participating in this study, she should inform her treating physician
immediately
- Participant must understand the investigational nature of this study and sign an
Independent Ethics Committee/Institutional Review Board approved written informed
consent form prior to receiving any study related procedure
Exclusion Criteria:
- Patients must not have any known contraindications to endocrine therapy, in the
opinion of the treating investigator
- Participants who have had chemotherapy, hormonal/endocrine therapy, immunotherapy,
biologics or radiotherapy (as well as any other investigational agents/devices)
within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
or those who have not recovered from adverse events due to agents administered more
than 4 weeks earlier
- Have a known history of hypersensitivity reactions attributed to compounds of
similar chemical or biologic composition to tamoxifen or any of its excipients
- Patients known or suspected to have hypercoagulable syndrome or with history of
venous or arterial thrombosis, stroke, transient ischemic attack (TIA), or pulmonary
embolism
- Known human immunodeficiency virus (HIV) positivity or acquired immunodeficiency
syndrome (AIDS) related illness
- Cardiac disease (history of and/or active disease) that would preclude the use of
the drugs included in the treatment regimen. This includes angina pectoris,
arrhythmias except for benign premature ventricular contractions, a history of
myocardial infarction, documented congestive heart failure (CHF) or cardiomyopathy
- Patients with cirrhosis or severe hepatic impairment
- Patients must not have a condition or an uncontrolled intercurrent illness
including, but not limited to any of the following: ongoing or active infection
requiring systemic treatment, except uncomplicated urinary tract infection (UTI), or
psychiatric illness/social situations that would limit compliance with study
requirements
- Pregnant or nursing female participants
- Unwilling or unable to follow protocol requirements
- Any condition which in the Investigator's opinion deems the participant an
unsuitable candidate to receive study drug
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Roswell Park Cancer Institute
Address:
City:
Buffalo
Zip:
14263
Country:
United States
Contact:
Last name:
Sheheryar Kabraji
Phone:
716-845-3429
Email:
Sheheryar.Kabraji@roswellpark.org
Investigator:
Last name:
Sheheryar Kabraji
Email:
Principal Investigator
Start date:
November 30, 2024
Completion date:
November 30, 2028
Lead sponsor:
Agency:
Roswell Park Cancer Institute
Agency class:
Other
Source:
Roswell Park Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06434064
