RECRUITING

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

Conditions

Breast Cancer Metastasis Androgen Receptor-positive HER2 negative Abemaciclib Bicalutamide

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

A Multicenter, Phase IB/II Study of Abemaciclib in Combination With Bicalutamide for Androgen Receptor-positive, HER2-negative Metastatic Breast Cancer

Quick Facts

Study Start:2021-09-20

Study Completion:2026-10

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05095207

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 90 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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) * 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: * 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"): * 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. * Post-menopausal status or receiving ovarian ablation with a GnRH agonist such as goserelin or leuprolide. Postmenopausal status is defined by any one of the following criteria: * Prior bilateral oophorectomy. * Age ≥ 60 years. * Age \< 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, or ovarian suppression) and FSH, LH, and estradiol in the postmenopausal range per local normal. * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).	* Treatment with any of the following: 1. Any investigational agents or study drugs from a previous clinical study within 28 days of the first dose of study treatment 2. Any other chemotherapy, immunotherapy or anticancer agents within 21 days of the first dose of study treatment 3. 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: 1. Mean resting corrected QT interval (QTc) \> 470 msec obtained from 3 consecutive electrocardiograms (ECGs) 2. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block) 3. 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 4. 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. 5. 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 6. Uncontrolled hypotension - Systolic BP \<90mmHg and/or diastolic BP \<50mmHg 7. Left ventricular ejection fraction (LVEF) below lower limit of normal for site * Prior history of DVT/PE or embolic stroke, unless currently on therapeutic anticoagulation * Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: 1. Absolute neutrophil count \< 1.5 x 109/L 2. Platelet count \< 100 x 109/L 3. Hemoglobin \< 8 g/L (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.) 4. Alanine aminotransferase \> 3 times the upper limit of normal (ULN) 5. Aspartate aminotransferase \> 3 times ULN 6. Total bilirubin \> 1.5 times ULN (patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted) 7. Creatinine \>1.5 times ULN concurrent with creatinine clearance \< 50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is \> 1.5 times ULN 8. Proteinuria 3+ on dipstick analysis or \>500mg/24 hours 9. Sodium or potassium outside normal reference range for site * Liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis. Patients who are hepatitis B Core antibody IgG positive are allowed to participate if taking and compliant with daily oral hepatitis B prophylactic medications * The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], 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). * Severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 89% or less at rest on room air * Uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN * Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption abemaciclib or bicalutamide * Patients with an active bleeding diathesis * The patient has active systemic 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. * History of hypersensitivity or allergic reaction to abemaciclib or bicalutamide, or drugs with a similar chemical structure or class * Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements * Co-administration with CYP3A4 inducers (e.g., phenytoin, rifampin, carbamazepine, St John's Wort, bosentan, efavirenz, etravirine, modafinil, and nafcillin), CYP3A4 inhibitors (e.g., clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, verapamil, and voriconazole), and CYP3A4 substrates (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, pimozide, quinidine, sirolimus and tacrolimus). See Appendix C for complete list. * Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin. * Female patients who are pregnant or breast feeding/lactating, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a method of contraception.

Inclusion Criteria

Exclusion Criteria

* 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)
* 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:
* 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"):
* 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.
* Post-menopausal status or receiving ovarian ablation with a GnRH agonist such as goserelin or leuprolide. Postmenopausal status is defined by any one of the following criteria:
* Prior bilateral oophorectomy.
* Age ≥ 60 years.
* Age \< 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, or ovarian suppression) and FSH, LH, and estradiol in the postmenopausal range per local normal.
* Has not undergone a hysterectomy or bilateral oophorectomy; or
* Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

* Treatment with any of the following:
1. Any investigational agents or study drugs from a previous clinical study within 28 days of the first dose of study treatment
2. Any other chemotherapy, immunotherapy or anticancer agents within 21 days of the first dose of study treatment
3. 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:
1. Mean resting corrected QT interval (QTc) \> 470 msec obtained from 3 consecutive electrocardiograms (ECGs)
2. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block)
3. 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
4. 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.
5. 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
6. Uncontrolled hypotension - Systolic BP \<90mmHg and/or diastolic BP \<50mmHg
7. Left ventricular ejection fraction (LVEF) below lower limit of normal for site
* Prior history of DVT/PE or embolic stroke, unless currently on therapeutic anticoagulation
* Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
1. Absolute neutrophil count \< 1.5 x 109/L
2. Platelet count \< 100 x 109/L
3. Hemoglobin \< 8 g/L (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.)
4. Alanine aminotransferase \> 3 times the upper limit of normal (ULN)
5. Aspartate aminotransferase \> 3 times ULN
6. Total bilirubin \> 1.5 times ULN (patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted)
7. Creatinine \>1.5 times ULN concurrent with creatinine clearance \< 50 ml/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is only required when creatinine is \> 1.5 times ULN
8. Proteinuria 3+ on dipstick analysis or \>500mg/24 hours
9. Sodium or potassium outside normal reference range for site
* Liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis. Patients who are hepatitis B Core antibody IgG positive are allowed to participate if taking and compliant with daily oral hepatitis B prophylactic medications
* The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], 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).
* Severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 89% or less at rest on room air
* Uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN
* Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption abemaciclib or bicalutamide
* Patients with an active bleeding diathesis
* The patient has active systemic 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.
* History of hypersensitivity or allergic reaction to abemaciclib or bicalutamide, or drugs with a similar chemical structure or class
* Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
* Co-administration with CYP3A4 inducers (e.g., phenytoin, rifampin, carbamazepine, St John's Wort, bosentan, efavirenz, etravirine, modafinil, and nafcillin), CYP3A4 inhibitors (e.g., clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, verapamil, and voriconazole), and CYP3A4 substrates (e.g., alfentanil, cyclosporine, dihydroergotamine, ergotamine, everolimus, fentanyl, pimozide, quinidine, sirolimus and tacrolimus). See Appendix C for complete list.
* Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
* Female patients who are pregnant or breast feeding/lactating, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a method of contraception.

Contacts and Locations

Study Contact

Laura A Fiedler, MPH

CONTACT

(646) 957-1407

laura.fiedler@mssm.edu

Esther Kim, CRC

CONTACT

esther.kim@mssm.edu

Principal Investigator

Amy Tiersten, MD

PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Study Locations (Sites)

Mount Sinai Beth Israel

New York, New York, 10003

United States

Mount Sinai - West

New York, New York, 10019

United States

Dubin breast Center

New York, New York, 10029

United States

Collaborators and Investigators

Sponsor: Icahn School of Medicine at Mount Sinai

Amy Tiersten, MD, PRINCIPAL_INVESTIGATOR, Icahn School of Medicine at Mount Sinai

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-09-20

Study Completion Date2026-10

Study Record Updates

Study Start Date2021-09-20

Study Completion Date2026-10

Terms related to this study

Keywords Provided by Researchers

Breast Cancer
Androgen Receptor-positive
HER2 negative
Abemaciclib
Bicalutamide

Additional Relevant MeSH Terms

Breast Cancer
Metastasis