Clinical Trial of Avasopasem in Patients With Metastatic Hormone Receptor Positive Breast Cancer With Progression on a CDK 4/6 Inhibitor and Hormonal Therapy

NCT ID: NCT07137871

Last Updated: 2025-10-31

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-02
• Study Completion Date: 2028-10-31

Brief Summary

This study aims to evaluate the safety of avasopasem in combination with CDK 4/6 inhibitor and hormonal therapy in women with metastatic hormone receptor positive breast cancer, and to see if the addition of avasopasem improves the effectiveness of a CDK 4/6 inhibitor and hormonal therapy.

Detailed Description

This is a phase 1 non-randomized clinical trial of Avasopasem in patients with metastatic hormone receptor positive breast cancer with progression on first line therapy consisting of a CDK 4/6 inhibitor and hormonal therapy to determine the efficacy and safety of the addition of Avasopasem in patients with metastatic HR+ breast cancer with progression after first line treatment with hormonal therapy (an AI or fulvestrant) and a CDK 4/6 inhibitor (ribociclib or abemaciclib). Each treatment cycle will be 28 days and tumor assessment by imaging with CT scans of the chest, abdomen and pelvis will be performed every two cycles.

Conditions

Breast Cancer Metastatic

Study Design

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

Study Groups

Metastatic Hormone Receptor Positive Breast Cancer

This study is investigating the addition of a novel agent, Avasopasem (or GC4419), in patients with hormonal receptor positive (HR+) metastatic breast cancer with progression while on treatment with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor and an aromatase inhibitor.

Group Type: EXPERIMENTAL

Avasopasem

Intervention Type: DRUG

Avasopasem has also been shown to exhibit both antitumor effects as well as minimal toxicity. Participants are currently taking a CDK 4/6 inhibitor and hormonal therapy

Interventions

Avasopasem

Avasopasem has also been shown to exhibit both antitumor effects as well as minimal toxicity. Participants are currently taking a CDK 4/6 inhibitor and hormonal therapy

Intervention Type: DRUG

Other Intervention Names

GC4419

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed diagnosis of HR+, HER2 negative metastatic breast cancer.
• Estrogen receptor (ER) and/or progesterone receptor (PR) expression positivity is defined as at least 10% of tumor cells nuclei positive by immunohistochemistry in the sample on testing.
• HER2 negative: defined as IHC staining of 0 or 1+. If HER2 overexpression is equivocal by IHC, defined as 2+, the tumor must be non-gene amplified by FISH (ratio <2 and HER2 copy number <4).
• Progression on treatment with a CDK 4/6 inhibitor and hormonal therapy in the metastatic setting

• The CDK 4/6 inhibitor must be ribociclib or abemaciclib. Patients on palbociclib are not eligible.
• Patient may have been on palbociclib previously but must have been stable on ribociclib or abemaciclib for at least three months prior to enrolling. In this case, the switch from palbociclib to either ribociclib or abemaciclib must have been of toxicity management and not progression of disease.
• Hormonal therapy is defined as an aromatase inhibitor (anastrozole, letrozole, exemestane) or fulvestrant.
• Patients on tamoxifen are not eligible.
• Both men and pre/perimenopausal women must be on ovarian suppression with a luteinizing hormone-releasing hormone (LHRH) agonist.
• Patients must have measurable disease based on RECIST 1.1 criteria.
• Females of child-bearing potential (FOCBP) who engage in intercourse must agree to use adequate contraception (e.g., hormonal or an intrauterine device [IUD] or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 3 weeks following completion of therapy.

NOTE: A FOCBP is any woman who meets the following criteria:

• Has not undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy
• Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months)

• FOCBP must have a negative serum pregnancy test within 7 days prior to registration.
• Patients must be ≥ 18 years of age at the time of signing consent.
• Patients must have an estimated life expectancy of at least 12 weeks.
• Patients must exhibit an ECOG performance status of 0 or 1.
• Patients must have adequate organ and bone marrow function as defined below:

• Leukocytes (WBC) ≥ 3,000/mcL
• Absolute neutrophil count (ANC) ≥ 1000/mcL
• Hemoglobin (Hgb) ≥ 7 g/dL
• Platelets (PLT) ≥ 100,000/mcL
• Total bilirubin < 1.5 x Institutional upper limit of normal (ULN); ≤ 3.0 x ULN for patients with Gilbert's syndrome
• AST (SGOT)/ALT (SGPT) < 3 x institutional ULN, or < 5 x ULN if liver metastasis present
• Creatinine < 1.5 Institutional ULN
• Patients with treated brain metastases are eligible if follow-up brain imaging at least 6 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression.
• Patients must have sufficient samples available to meet Menarini Silicon Biosystems (MSB) specimen requirements.
• Patients with known history or current symptoms of cardiac disease, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• Patients must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

• Patients who have any systemic therapy in the metastatic setting except hormonal therapy in combination with a CDK 4/6 inhibitor. Previously palliative targeted radiation therapy is allowed. Bone targeting agents such as bisphosphonates and rank ligand inhibitors for metastatic breast cancer to the bone is also allowed prior and during this trial.
• Patients with untreated new or progressive brain metastases or leptomeningeal disease
• Use of concomitant nitrates and PDE5 inhibitors.
• Use of potent CYP3A4 inhibitors or inducers and not able to discontinue two weeks prior to enrolling onto the trial.
• Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints. Note: Patients with HIV or infectious hepatitis must exhibit well controlled disease with stable treatment regimen (where applicable) that in the opinion of the treating physician should not preclude them from participating in the study.
• Patients who are currently pregnant or breast feeding.
• Patients with a history of another invasive malignancy within 2 years of registration with the exception of local squamous cell or basal cell carcinoma of the skin.

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

Sponsors

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role: lead

Responsible Party

Kate Lathrop

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kate Lathrop, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center at San Antonio

Locations

Mays Cancer Center, UT Health San Antonio

San Antonio, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Kate Lathrop, MD

Role: CONTACT

lathrop@uthscsa.edu

210-450-1000

Facility Contacts

Kayla Chamberlin, RN

Role: primary

chamberlink@uthscsa.edu

210-450-1000

Kate Lathrop, MD

Role: backup

lathrop@uthscsa.edu

210-450-1000

Other Identifiers

STUDY00000816

Identifier Type: OTHER

Identifier Source: secondary_id

CTMS# 24-0096

Identifier Type: -

Identifier Source: org_study_id