Tamoxifen and Pegylated Liposomal Doxorubicin for the Treatment of Patients With Metastatic or Inoperable, Locally Advanced Triple Negative Breast Cancer

NCT ID: NCT06434064

Last Updated: 2025-12-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-15
• Study Completion Date: 2028-11-30

Brief 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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (tamoxifen, pegylated liposomal doxorubicin)

Patients receive tamoxifen PO QD on days 1-28 of each cycle and pegylated liposomal doxorubicin IV on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography, CT scan or MRI, tumor biopsy, and blood sample collection throughout the study.

Group Type: EXPERIMENTAL

Biopsy

Intervention Type: PROCEDURE

Undergo tumor biopsy

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type: PROCEDURE

Undergo CT scan

Echocardiography

Intervention Type: PROCEDURE

Undergo echocardiography

Magnetic Resonance Imaging

Intervention Type: PROCEDURE

Undergo MRI

Pegylated Liposomal Doxorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Tamoxifen

Intervention Type: DRUG

Given PO

Interventions

Biopsy

Undergo tumor biopsy

Intervention Type: PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type: PROCEDURE

Computed Tomography

Undergo CT scan

Intervention Type: PROCEDURE

Echocardiography

Undergo echocardiography

Intervention Type: PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type: PROCEDURE

Pegylated Liposomal Doxorubicin Hydrochloride

Given IV

Intervention Type: DRUG

Tamoxifen

Given PO

Intervention Type: DRUG

Other Intervention Names

BIOPSY_TYPE; Bx; Biological Sample Collection; Biospecimen Collected; Specimen Collection; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized axial tomography (procedure); Computerized Tomography; Computerized Tomography (CT) scan; CT; CT Scan; tomography; EC; Magnetic Resonance; Magnetic Resonance Imaging (MRI); Magnetic resonance imaging (procedure); Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI; MRI Scan; MRIs; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; sMRI; Structural MRI; ATI-0918; Caelyx; Dox-SL; Doxil; Doxilen; Doxorubicin HCl Liposomal; Doxorubicin HCl Liposome; Doxorubicin Hydrochloride Liposome; Duomeisu; Evacet; LipoDox; Lipodox 50; Liposomal Adriamycin; Liposomal Doxorubicin Hydrochloride; Liposomal-Encapsulated Doxorubicin; Pegylated Doxorubicin HCl Liposome; Pegylated Liposomal Doxorubicin; S-Liposomal Doxorubicin; Stealth Liposomal Doxorubicin; TLC D-99; TMX

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 a confirmed TP53 mutation, as determined by the Roswell Park Oncomine™ Precision Assay (OPA) (see Appendix J ), using either an archival metastatic tumor sample or, if unavailable, a fresh biopsy
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roswell Park Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sheheryar Kabraji

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Sheheryar Kabraji

Role: primary

Sheheryar.Kabraji@roswellpark.org

716-845-3429

Other Identifiers

NCI-2024-03909

Identifier Type: REGISTRY

Identifier Source: secondary_id

I-3671523

Identifier Type: OTHER

Identifier Source: secondary_id

I-3671523

Identifier Type: -

Identifier Source: org_study_id