Sequential Therapies Modeled on Evolutionary Dynamics for Breast Cancer

A Pilot Study of Sequential ("First Strike, Second Strike") Therapies, Modeled on Evolutionary Dynamics of Anthropocene Extinctions, for Hormone Positive Metastatic Breast Cancer

The purpose of the study is to test a treatment strategy with currently approved drugs to see if it is practical to administer the available drugs in a new way that researchers hope could be more effective in treating metastatic breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Taxotere; Drug: Cytoxan; Drug: Trastuzumab deruxtecan; Drug: Sacituzumab govitecan; Drug: Xeloda; Drug: Fulvestrant; Drug: Ribociclib; Drug: Abemaciclib

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Luza Herrera Dominguez; Phone Number: 813-745-5332; Email: Luza.Herrera@moffitt.org

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Principal Investigator: Aixa Soyano, MD
      • Sub-Investigator: Dana Ataya, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female patients 18 years or older
• Histologically or cytologically confirmed diagnosis of hormone positive HER2 negative metastatic breast cancer per ASCO/CAP criteria (Allison et al, 2020, Wolff et al, 2018), with diagnosis established through either a breast/axillary biopsy or biopsy of a metastatic lesion.
• Hormone positive MBC previously treated with endocrine therapy with either an aromatase inhibitor or Tamoxifen (alone or in combination with a CDK4/6 inhibitor).
• Elevated breast tumor markers which may include cancer antigen 15-3 (CA 15-3) levels above the institutional upper limit of normal (ULN) range of 0.0-31.0 U/mL, cancer antigen 27-29 (CA 27-29) (range <38 U/mL) and/or elevated Carcinoembryonic antigen (CEA) above institutional upper limit of normal (range 0.0 - 5.2 ng/mL).
• Presence of measurable disease on imaging via RECIST v1.1.
• ECOG performance status 0-1.
• Participants must have adequate organ and marrow function as defined in the protocol.
• A negative pregnancy test for pre-menopausal women of childbearing potential.
• Pre-menopausal women of childbearing potential who are sexually active with a male partner must agree to use adequate contraception prior to the study, for the duration of study participation.
• Inclusion of minorities: patients of all races and ethnic groups who meet the above inclusion and below exclusion criteria are eligible for this trial.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Ability to understand and the willingness to sign a written informed consent document or have a legally authorized representative sign on the participant's behalf.

Exclusion Criteria:

• Have previously received Fulvestrant for treatment of their breast cancer.
• History of allergic reactions attributed to the study drugs.
• Documented brain metastasis or active or newly diagnosed CNS metastases, including meningeal carcinomatosis, because systemic treatment would need to be paused for these patients.
• Treatment with any investigational compound within 30 days prior to the first dose of study drugs or during this study.
• Diagnosis or treatment for another systemic malignancy within 2 years before the first dose of study drugs, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Uncontrolled intercurrent illness including-but not limited to-ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term, including massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome.
• Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HBsAg]), or hepatitis C (HCV). Participants with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Participants with positive HCV antibody are eligible if polymerase chain reaction is negative for HCV RNA.
• Concurrent or prior use of immunosuppressive medication within 14 days before the first dose of study drugs, with the following exceptions: premedication with dexamethasone, intranasal, inhaled, topical or local steroid injections, systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or its equivalent; steroids as premedication for hypersensitivity reactions (e.g., premedication for iodinated contrast allergy before CT scan).
• Inability to comply with protocol requirements.
• Pregnant and/or breastfeeding women are excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sequential therapy; In this study sequential therapies will be administered. Strike 1: Cytoxan/Taxotere/GM-CSF Strike 2: Sacituzumab govitecan or trastuzumab deruxtecan Strike 3: Capecitabine Strike 4: Fulvestrant + CDK 4/6 inhibitor (ribociclib or abemaciclib)

Drug: Taxotere; 75 mg/m2 once every 21 days for 4 cycles; Other Names: Docetaxel; Drug: Cytoxan; 600 mg/m2 once every 21 days for 4 cycles; Other Names: Cyclophosphamide; Drug: Trastuzumab deruxtecan; 5.4 mg/kg once every 21 days for 5 cycles; Other Names: Enhertu; Drug: Sacituzumab govitecan; 10 mg/kg on days 1 and 8 cycled every 21 days for 5 cycles; Other Names: Trodelvy; Drug: Xeloda; 1000 mg/m2 orally twice daily for 14 days cycled every 21 days for 5 cycles; Other Names: Capecitabine; Drug: Fulvestrant; 500 mg intramuscular (IM) on days 1, 15 and 28 of the first cycle followed by every 28 days for a total of 4 cycles; Other Names: Faslodex; Drug: Ribociclib; 600 mg orally daily 21 days on, 7 days off; Other Names: Kisqali; Drug: Abemaciclib; 150 mg by mouth twice daily; Other Names: Verzenio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of Sequential Therapy	The proportion of patients able to complete the sequence of therapies by the conclusion of the trial.	Up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	The proportion of patients who experience adverse events or serious adverse events.	Up to 18 months
No Evidence of Disease (NED)	The proportion of patients who are able to reach NED status by the conclusion of the trial will be calculated.	Up to 18 months

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Investigators: Principal Investigator: Aixa Soyano, MD, Moffitt Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: May 7, 2024
• First Submitted That Met QC Criteria: May 7, 2024
• First Posted (Actual): May 10, 2024

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Polycyclic Compounds; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Steroids; Fused-Ring Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Nucleosides; Uracil; Pyrimidinones; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Deoxyribonucleosides; Fluorouracil; Docetaxel; Capecitabine; Fulvestrant; Cyclophosphamide; abemaciclib; trastuzumab deruxtecan; ribociclib; sacituzumab govitecan
• Other Study ID Numbers: MCC-22617

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No