Abemaciclib in Combination With Bicalutamide for Androgen Receptor-positive, HER2-negative Metastatic Breast Cancer

NCT05095207 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: GCO 21-0699
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open label multicenter, Phase IB/II Study of Abemaciclib in Combination with Bicalutamide for Androgen Receptor-positive, HER2-negative Metastatic Breast Cancer

Conditions

Breast Cancer; Metastasis

Keywords

Breast Cancer; Androgen Receptor-positive; HER2 negative; Abemaciclib; Bicalutamide

Outcome Measures

Primary Outcomes (1)

• The Dose-Limiting Toxicity (DLT) and Recommended Phase II Dose (RP2D)

  For the Phase 1 portion of the trial Bayesian optimal interval (BOIN) design is being used. a minimum of 3 and a maximum of 12 patients enrolled to determine the dose-limiting toxicity (DLT) and will be the recommended phase II dose (RP2D). • A DLT will be defined as: * Grade 3 or 4 non-hematologic toxicity * Grade 3 neutropenia lasting greater than 21 days * Grade 3 or 4 neutropenia with neutropenic fever * Grade 4 hematologic toxicity events experienced within the first 4 weeks (1 cycle) of study treatment. These will be assessed via National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] v.5.0 toxicity criteria. The DLT period will be the first cycle (28 days) of therapy.

  12 weeks

Secondary Outcomes (2)

• Frequency of Adverse Events (AE)

  12 weeks

• Disease Control Rate (DCR)

  12 weeks

Study Arms (1)

Participants with Androgen Receptor-positive, HER2-negative Metastatic Breast Cancer

EXPERIMENTAL

Abemaciclib in Combination with Bicalutamide

Drug: Abemaciclib; Drug: Bicalutamide

Interventions

Abemaciclib DRUG

100 mg orally twice daily, day 1 to 28. If no toxicity in cycle 1 for the first 3 patients, increase dose to 150mg orally twice daily day 1-28 and enroll 3 patients. If excessive toxicity experienced at 100mg orally twice daily dose, decrease dose to 50mg orally twice daily day 1-28.

Participants with Androgen Receptor-positive, HER2-negative Metastatic Breast Cancer

Bicalutamide DRUG

150 mg orally daily, day 1 to 28.

Participants with Androgen Receptor-positive, HER2-negative Metastatic Breast Cancer

Eligibility Criteria

• Age: 18 Years - 90 Years
• Gender Eligibility Details: All Female All Male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
• If a patient declines to participate in any voluntary exploratory research and/or genetic component of the study, there will be no penalty or loss of benefit to the patient and he/she will not be excluded from other aspects of the study
• Women aged at least 18 years
• The patient has a biopsy-confirmed diagnosis of recurrent, unresectable, locally advanced, or metastatic HER2neu-negative breast cancer (including bone-only metastatic disease) o The patient must have had biopsy confirmation of a metastatic site (with appropriate ER/PR/HER2neu IHC staining)
• o The patient has measurable or evaluable disease as evidenced on pre-treatment baseline CT chest, abdomen, and pelvis with bone scan OR PET/CT
• The patient has AR+ breast cancer (defined as \> or equal to 1% staining on immunohistochemistry of metastatic breast cancer specimen)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks
• If the patient has ER+ or PR+ (\>1% on IHC) metastatic breast cancer:
• o patient must have had 1 prior line of endocrine therapy in the metastatic setting
• prior CDK4/6 inhibitor exposure allowed (abemaciclib. palbociclib, or ribociclib)
• no more than 2 prior line of cytotoxic chemotherapy in the metastatic setting allowed
• If the patient has ER-,PR-, HER2- metastatic breast cancer ("triple-negative"):
• o The patient may have had up to 4 prior lines of chemotherapy in the metastatic setting and at least 1 prior line of chemotherapy in the metastatic setting
• 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 21 days is required between last chemotherapy dose and randomization (provided the patient did not receive radiotherapy).
• Patients who received 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.

You may not qualify if:

• Treatment with any of the following:
• Any investigational agents or study drugs from a previous clinical study within 28 days of the first dose of study treatment
• Any other chemotherapy, immunotherapy or anticancer agents within 21 days of the first dose of study treatment
• Any prior exposure to anti-androgen therapy (bicalutamide, abiraterone, and/or enzalutamide)
• Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study treatment
• Spinal cord compression, leptomeningeal carcinomatosis, or brain metastases - unless asymptomatic, treated and stable and not requiring steroids for at least 2 weeks prior to start of study treatment
• Concurrent use of endocrine therapy (tamoxifen, anastrozole, letrozole, exemestane, oral contraceptive pills)
• As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) \> 470 msec obtained from 3 consecutive electrocardiograms (ECGs)
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block)
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, abnormalities in serum electrolytes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval
• Personal history of syncope of cardiovascular etiology, ventricular arrhythmia (of pathologic origin including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure NYHA Grade 2 or greater
• Uncontrolled hypotension - Systolic BP \<90mmHg and/or diastolic BP \<50mmHg

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (3)

Mount Sinai Beth Israel

New York, New York, 10003, United States

RECRUITING

Mount Sinai - West

New York, New York, 10019, United States

RECRUITING

Dubin breast Center

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

abemaciclib; bicalutamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Amy Tiersten, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura A Fiedler, MPH

CONTACT

(646) 957-1407; laura.fiedler@mssm.edu

Esther Kim, CRC

CONTACT

esther.kim@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor - Hematology Oncology

Model Details: For the Phase 1 portion of the trial Bayesian optimal interval (BOIN) design is being used. a minimum of 3 and a maximum of 12 patients enrolled to determine RP2D. The 3-9 patients evaluated at the RP2D of the Phase I part of the trial will be enrolled and included in the Phase II part of the trial. If 2 or fewer among 12 patients in the first stage of Phase II have disease control, the trial will stop. However, if at least 3 have disease control in the first stage, then an additional 33 patients will be enrolled in the second stage, for a total of 46 patients. If among the 46 patients, 12 or fewer achieved complete response, partial response or stable disease, the treatment regimen under investigation in this trial will be rejected; or if at least 13 out of the 46 patients respond, the treatment regimen will be considered worthy of further study. The total sample size for Phase I and II portions combined is a minimum of 3 and a maximum of 60.

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: October 27, 2021
• Study Start: September 20, 2021
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ('learned intermediary') identified for this purpose. To achieve aims in the approved proposal. Information will be made once available

Locations

US (3)