Phase Ib/II Trial of Abemaciclib and Elacestrant in Patients With Brain Metastasis Due to HR+/Her2- Breast Cancer

NCT04791384 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: Lilly-I3Y-US-I026
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 4

Brief Summary

This is a multi-institutional, single arm, open label, Phase Ib/II study of abemaciclib in combination with elacestrant in patients with HR+/Her2- breast cancer metastatic to the brain. Patients may have received up to two prior lines of systemic chemotherapy for locally advanced or metastatic disease. There will be no limit on prior use of endocrine therapy including aromatase inhibitors, tamoxifen and fulvestrant, given a documented clinical benefit of elacestrant in this setting.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• The number of patients in Phase 1b part of the study with any adverse events (AE).

  To determine the safety and tolerability of the abemaciclib and elacestrant combination. We will assess the incidence, nature and severity of all adverse events (AE) that occur on or after C1D1 of therapy, AE severities will be classified using the CTCAE criteria.

  1.5 years

• Assess the efficacy of the drug combination abemaciclib and elacestrant.

  Determine the overall intracranial response rate (OIRR; complete and partial response) and clinical benefit rate (CBR) as defined by brain metastasis response criteria (RANO-BM) in women with HR+ / Her2- breast cancer using the sum of study participants who experience complete response or partial response within 24 weeks or less. This assessment will look at tumor responses conducted before patients start treatment, at timepoints while receiving treatment, and at treatment end.

  The whole study- 2.5 years

Secondary Outcomes (3)

• Evaluate tumor response rates of treatment with abemaciclib and elacestrant combination.

  2.5 years

• Evaluate duration of tumor response rates of treatment with abemaciclib and elacestrant combination.

  2.5 years

• The percentage of patients to complete the study.

  2.5 years

Study Arms (1)

Abemaciclib/Elacestrant

EXPERIMENTAL

Abemaciclib and Elacestrant combination

Drug: Abemaciclib; Drug: Elacestrant

Interventions

Elacestrant DRUG

taken orally

Abemaciclib/Elacestrant

Abemaciclib DRUG

taken orally

Also known as: Verzenio

Abemaciclib/Elacestrant

Eligibility Criteria

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

You may qualify if:

• Post-menopausal women with histologically or cytologically diagnosed metastatic HR+/Her2- breast cancer defined as positive for estrogen receptor or progesterone receptor (more than 1% staining by immunohistochemistry, as defined in 2010 ASCO recommendations, Hammond 2010) and negative for HER2 amplification (immunohistochemistry result of 0-1+, or a negative in situ hybridization).
• Post-menopausal status is defined as:
• Documented surgical bilateral oophorectomy
• Age \> 59 years with amenorrhea for \> 1 year since last menses
• Age \< 60 years with amenorrhea for \> 1 year since last menses and serum estradiol and FSH in post-menopausal laboratory range.
• Patients must have measurable brain metastasis (patients with leptomeningeal disease and measurable parenchymal disease are permitted) with documented intracranial disease progression. One measurable lesion \>10mm, or previously irradiated lesion with increase in size by at least 5mm as defined by RANO-BM criteria and revised RECIST criteria (version 1.1, Appendix C). Patients with prior whole brain radiotherapy are permitted.
• Prior treatment with up to two lines of systemic chemotherapy for metastatic disease and two weeks from any previous anticancer therapy including biologics and recovered from expected toxicity; at least 4 weeks from major surgery and recovered; at least 3 weeks from radiation affecting more than 25% of bone marrow and recovered; and 2 weeks from other palliative radiation and recovered.
• ECOG performance status ≤ 2 (see Appendix B).
• Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization. A washout period of at least 14 days is required between last chemotherapy dose and randomization (provided the patient did not receive radiotherapy
• Patients who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and randomization.
• The patient has adequate organ function for all of the following criteria, as defined in Table 1 below.
• Table 1: Laboratory Value Guidance to Establish Adequate Organ Function System Laboratory Value Hematologic ANC: \>/= 1.5 × 109/L Platelets: \>/=100 × 109/L Hemoglobin: \>/=8 g/dL
• Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
• Hepatic Total bilirubin: \</= 1.5 × ULN Patients with Gilbert's syndrome with a total bilirubin \</=2.0 times ULN and direct bilirubin within normal limits are permitted.
• ALT and AST: \</= 3 × ULN

You may not qualify if:

• Women who are pregnant or lactating and men.
• Patients under age of 18
• Prior use of abemaciclib or elacestrant (use of other cdk4/6 inhibitors are allowed)
• The patient has serious preexisting medical condition(s) that would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• The patient has active bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment.
• The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• Wome who are pre-menopausal (women with chemically induced menopause are eligible).
• More than two seizures in the last 4 weeks.
• Have uncontrolled serious medical or psychiatric illness.
• Have any medical condition that would impair the administration of oral agents including recurrent bowel obstructions, inflammatory bowel disease or uncontrolled nausea, vomiting. Baseline grade 2 or greater diarrhea.
• Have an additional malignancy diagnosed within 5 years of study enrollment with the exception of basal or squamous cell skin cancer or cervical cancer in situ.
• Patients may not be receiving any other investigational agents. A washout period of 14 days is required for all prior anti-cancer therapies.

Sponsors & Collaborators

• Criterium, Inc.: lead

Study Sites (4)

University of Colorado

Aurora, Colorado, 80045, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Cancer Care Northwest

Spokane Valley, Washington, 99216, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

abemaciclib; elacestrant

Condition Hierarchy (Ancestors)

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

Study Officials

• Peter Kabos, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2020
• First Posted: March 10, 2021
• Study Start: April 21, 2022
• Primary Completion: September 16, 2024
• Study Completion: September 17, 2024
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

US (4)