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

NCT06434064 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: I-3671523NCI-2024-03909
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Locally Advanced Unresectable Triple-Negative Breast Carcinoma; Metastatic Triple-Negative Breast Carcinoma; Anatomic Stage III Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Will be summarized using frequencies and relative frequencies.

  Up to 4 years

Secondary Outcomes (4)

• Incidence of adverse events

  Until progression or end of treatment, up to 4 years

• Duration of response

  From initial response to disease progression (per RECIST version1.1) up to 4 years

• Overall survival

  From treatment initiation until death due to any cause, up to 4 years

• Progression free survival

  From treatment initiation until disease progression or death due to any cause, up to 4 years

Study Arms (1)

Treatment (tamoxifen, pegylated liposomal doxorubicin)

EXPERIMENTAL

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.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography; Procedure: Magnetic Resonance Imaging; Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Drug: Tamoxifen

Interventions

Biopsy PROCEDURE

Undergo tumor biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (tamoxifen, pegylated liposomal doxorubicin)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (tamoxifen, pegylated liposomal doxorubicin)

Tamoxifen DRUG

Given PO

Also known as: TMX

Treatment (tamoxifen, pegylated liposomal doxorubicin)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (tamoxifen, pegylated liposomal doxorubicin)

Echocardiography PROCEDURE

Undergo echocardiography

Also known as: EC

Treatment (tamoxifen, pegylated liposomal doxorubicin)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: 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

Treatment (tamoxifen, pegylated liposomal doxorubicin)

Pegylated Liposomal Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 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

Treatment (tamoxifen, pegylated liposomal doxorubicin)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 eligible TP53 genomic alteration, as determined by the Roswell Park Oncomine™ Precision Assay (OPA) or similar CLIA-approved assay, using either an archival metastatic tumor sample or, if unavailable, a fresh biopsy. Uncertainty about the eligibility of the TP53 genomic alteration for this study can be resolved by discussion with the study PI
• 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

You may not qualify if:

• 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 Cycle 1 Day 1 (6 weeks for nitrosoureas or mitomycin C), 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; liposomal doxorubicin; Doxorubicin; Tamoxifen

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Stilbenes; Benzylidene Compounds; Benzene Derivatives

Study Officials

• Sheheryar Kabraji

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2024
• First Posted: May 30, 2024
• Study Start: March 15, 2026
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: March 2, 2026

Record last verified: 2026-02

Locations

US (1)