Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Up to 3 single ascending doses of GMI-1359 followed by the highest tolerated dose given for 3 consecutive days.

GMI-1359

Jeremy Force, DO

Dorothy A Sipkins, MD, PhD

This trial is being conducted to investigate the safety, tolerability, pharmacokinetics (the effect the body has on the drug), and pharmacodynamics (the effect the drug has on the body) of GMI-1359 when given with standard-of-care treatment to subjects with HR+ metastatic breast cancer.

A Study to Determine Safety and Tolerability of GMI-1359 in Subjects With HR+ Metastatic Breast Cancer

A Phase 1b, Single and Multiple Dose, Open-Label Trial of Intravenous GMI-1359 in HR+ Metastatic Breast Cancer Subjects

GlycoMimetics Incorporated

Symptoms and General Pathology

Nervous System Diseases

Neoplasm Metastasis

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

All Drugs and Chemicals

Antineoplastic Agents

Hormones

Fulvestrant

Aromatase Inhibitors

Hormone Antagonists

Treatment will be initiated with one week of abemaciclib followed by stereotactic radiation to sites of brain metastases or post-operative cavities with continued abemaciclib. In the phase I portion, safety will be monitored initially by a 3+3 design. If unexpected neurologic toxicities are noted, the dose of radiation therapy will be modified.

Treatment will be initiated with one week of abemaciclib followed by stereotactic radiation at the phase 1 dose to sites of brain metastases or post-operative cavities with continued abemaciclib.

Patients will receive single session SRS to intact brain metastases and post-operative cavities. For intact brain metastases, this will be 15 Gy to lesions between 31-40 mm, 18 Gy to 21- 30 mm, and 24 Gy to lesions measuring ≤ 20 mm.

Stereotactic Radiosurgery (SRS)

Abemaciclib is an orally administered selective small-molecule inhibitor of CDK4 and CDK6 that is 14 times more potent against CDK4 than CDK6 in enzymatic assays that is approved for the treatment of advanced or metastatic breast cancers. Abemaciclib will be administered at a dose of 150 mg twice daily.

Abemaciclib

Abemaciclib will be administered with standard of care endocrine therapy. Endocrine therapy can consist of fulvestrant or an aromatase inhibitor. Dosing of concurrent endocrine therapy with abemaciclib should follow standard dosing and safety guidelines.

Endocrine therapy

Kamran A Ahmed, MD

Michelle DeJesus

Avan Armaghani, MD

John Arrington, MD

Ricardo Costa, MD, MSc

Arnold Etame, MD, PhD

Peter Forsyth, MD

Hung Khong, MD

James Liu, MD

Daniel Oliver, MD

Marilin Rosa, MD

Hatem Soliman, MD

Aixa Soyano Muller, MD

Nam Tran, MD, PhD

Michael Vogelbaum, MD, PhD

Michael Yu, MD

Heather Han, MD

This is a single arm study of abemaciclib and endocrine therapy with stereotactic radiosurgery (SRS) among patients with hormone receptor (HR)+/HER2- metastatic breast cancer brain metastases.

The study is designed as a prospective, single-arm, nonrandomized, open-label, phase I/II trial of abemaciclib and endocrine therapy with stereotactic radiosurgery (SRS) among patients with hormone receptor (HR)+/HER2- metastatic breast cancer brain metastases. Treatment will be initiated with one week of abemaciclib followed by stereotactic radiation to sites of brain metastases or post-operative cavities with continued abemaciclib. Safety will be monitored initially by a 3+3 design. This will be followed by a phase 2 study to evaluate intracranial progression free survival (PFS). If unexpected neurologic toxicities are noted, the dose of radiation therapy will be modified.

Stereotactic Radiation & Abemaciclib in the Management of HR+/HER2- Breast Cancer Brain Metastases

Phase I/II Study of Stereotactic Radiation and Abemaciclib in the Management of Hormone Receptor Positive HER2 Negative Breast Cancer Brain Metastases

Intracranial Progression Free Survival: defined as the time from the date of start of treatment to investigator-determined date of progression or death due to any cause, whichever comes first. Progression will be determined by Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) Criteria.

Intracranial local brain tumor control following SRS and abemaciclib will be determined from irradiated lesions according to RANO-BM criteria.

Intracranial distant brain tumor control following SRS and abemaciclib will determined by the development of new lesions outside of the irradiated area.

Extracranial Progression Free Survival: Time from the date of start of treatment to the investigator determined date of progression (determined by RECIST) or death due to any cause, whichever occurs first.

Overall Survival is defined as the time from the start of treatment to death due to any cause.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study to Determine Safety and Tolerability of GMI-1359 in Subjects With HR+ Metastatic Breast Cancer	NCT04197999	HR+ Metastatic ... Breast Cancer Breast Cancer M...	GMI-1359	18 Years -	GlycoMimetics Incorporated
Stereotactic Radiation & Abemaciclib in the Management of HR+/HER2- Breast Cancer Brain Metastases	NCT04923542	Brain Metastase... HR+ Metastatic ...	Stereotactic Ra... Abemaciclib Endocrine thera...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for hr+ metastatic breast cancer