Tamoxifen plus pegylated liposomal doxorubicin for advanced triple-negative breast cancer
A Pilot, Single-Arm, Phase II Trial of Tamoxifen Plus Pegylated Liposomal Doxorubicin in Patients With Metastatic Triple Negative Breast Cancer
This trial tests whether combining tamoxifen with pegylated liposomal doxorubicin can shrink or control metastatic or inoperable locally advanced triple-negative breast cancer in patients with low ER expression and a confirmed TP53 genomic alteration who have had prior therapies.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Roswell Park Cancer Institute Academic / other |
| Drugs / interventions | chemotherapy, immunotherapy, doxorubicin |
| Locations | 1 site (Buffalo, New York) |
| Trial ID | NCT06434064 on ClinicalTrials.gov |
What this trial studies
This is a phase II, single-center trial combining tamoxifen and pegylated liposomal doxorubicin in patients with metastatic or unresectable locally advanced triple-negative breast cancer (ER ≤10%, HER2-negative) who carry a confirmed TP53 genomic alteration. The primary endpoint is overall response rate by RECIST v1.1, with secondary endpoints including safety, progression-free survival, overall survival, and duration of response. The protocol requires baseline and on-treatment imaging, tumor biopsy or archival tissue for genomic confirmation, and serial blood draws for ctDNA and immune biomarker analyses. Exploratory objectives include RNA-sequencing, tumor microenvironment profiling, and analysis of ERβ–mutant p53 interactions.
Who should consider this trial
Good fit: Adults with metastatic or inoperable locally advanced triple-negative (ER ≤10%, HER2-negative) breast cancer who have a confirmed TP53 genomic alteration and have received at least two prior lines of metastatic therapy are ideal candidates.
Not a fit: Patients without a confirmed TP53 alteration, with ER expression above 10% or HER2-positive disease, or those unable to tolerate anthracycline therapy or required biopsies are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, the combination could increase response rates and prolong disease control for a subset of heavily pretreated TNBC patients with TP53 alterations.
How similar studies have performed: Pegylated liposomal doxorubicin has shown activity in breast cancer, but combining it with tamoxifen specifically for TNBC guided by TP53 status is a novel approach with limited prior clinical evidence.
Eligibility criteria
Show full inclusion / exclusion 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 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 * 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 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
Where this trial is running
Buffalo, New York
- Roswell Park Cancer Institute — Buffalo, New York, United States (Recruiting)
Study contacts
- Principal investigator: Sheheryar Kabraji — Roswell Park Cancer Institute
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.