RECRUITING

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

Conditions

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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 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.

Official Title

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

Quick Facts

Study Start:2022-04-21

Study Completion:2025-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04791384

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

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Patients will be eligible for inclusion in this study if all of the following criteria apply: 1. 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). 1. Documented surgical bilateral oophorectomy 2. Age \> 59 years with amenorrhea for \> 1 year since last menses 3. Age \< 60 years with amenorrhea for \> 1 year since last menses and serum estradiol and FSH in post-menopausal laboratory range. 2. 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. 3. 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. 4. ECOG performance status ≤ 2 (see Appendix B). 5. 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 6. 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. 7. The patient has adequate organ function for all of the following criteria, as defined in Table 1 below. 8. Ability to take oral medications. 9. Women of child-producing potential must agree to use effective contraceptive methods prior to study entry, during study participation, and for at least 30 days after the last administration of study medication. A serum pregnancy test within 72 hours prior to the initiation of therapy will be required for women of childbearing potential. 10. Have the ability to understand the requirements of the study, provide written informed consent which includes authorization for release of protected health information, abide by the study restrictions, and agree to return for the required assessments. 11. Availability of archival tumor tissue (core biopsy or surgical tumor blocks) for analysis. Sites will be asked to submit archival tissue (subjects may start the study if tissue is available at an outside hospital, but not yet requested or received).	* Patients will not be eligible for inclusion in this study if any of the following criteria apply: 1. Women who are pregnant or lactating and men. 2. Patients under age of 18 3. Prior use of abemaciclib or elacestrant (use of other cdk4/6 inhibitors are allowed) 4. 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). 5. 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. 6. 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. 7. Wome who are pre-menopausal (women with chemically induced menopause are eligible). 8. More than two seizures in the last 4 weeks. 9. Have uncontrolled serious medical or psychiatric illness. 10. 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. 11. 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. 12. Patients may not be receiving any other investigational agents. A washout period of 14 days is required for all prior anti-cancer therapies.

Inclusion Criteria

Exclusion Criteria

* Patients will be eligible for inclusion in this study if all of the following criteria apply:
1. 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).
1. Documented surgical bilateral oophorectomy
2. Age \> 59 years with amenorrhea for \> 1 year since last menses
3. Age \< 60 years with amenorrhea for \> 1 year since last menses and serum estradiol and FSH in post-menopausal laboratory range.
2. 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.
3. 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.
4. ECOG performance status ≤ 2 (see Appendix B).
5. 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
6. 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.
7. The patient has adequate organ function for all of the following criteria, as defined in Table 1 below.
8. Ability to take oral medications.
9. Women of child-producing potential must agree to use effective contraceptive methods prior to study entry, during study participation, and for at least 30 days after the last administration of study medication. A serum pregnancy test within 72 hours prior to the initiation of therapy will be required for women of childbearing potential.
10. Have the ability to understand the requirements of the study, provide written informed consent which includes authorization for release of protected health information, abide by the study restrictions, and agree to return for the required assessments.
11. Availability of archival tumor tissue (core biopsy or surgical tumor blocks) for analysis. Sites will be asked to submit archival tissue (subjects may start the study if tissue is available at an outside hospital, but not yet requested or received).

* Patients will not be eligible for inclusion in this study if any of the following criteria apply:
1. Women who are pregnant or lactating and men.
2. Patients under age of 18
3. Prior use of abemaciclib or elacestrant (use of other cdk4/6 inhibitors are allowed)
4. 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).
5. 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.
6. 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.
7. Wome who are pre-menopausal (women with chemically induced menopause are eligible).
8. More than two seizures in the last 4 weeks.
9. Have uncontrolled serious medical or psychiatric illness.
10. 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.
11. 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.
12. Patients may not be receiving any other investigational agents. A washout period of 14 days is required for all prior anti-cancer therapies.

Contacts and Locations

Study Contact

Raquel Lopez

CONTACT

518-583-0095

rlopez@criteriuminc.com

Ruth Stone

CONTACT

518-583-0095

restone@criteriuminc.com

Principal Investigator

Peter Kabos, MD

PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Study Locations (Sites)

University of Colorado

Aurora, Colorado, 80045

United States

Duke Cancer Center

Durham, North Carolina, 27710

United States

Cancer Care Northwest

Spokane Valley, Washington, 99216

United States

Collaborators and Investigators

Sponsor: Criterium, Inc.

Peter Kabos, MD, PRINCIPAL_INVESTIGATOR, University of Colorado, Denver

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 Date2022-04-21

Study Completion Date2025-01

Study Record Updates

Study Start Date2022-04-21

Study Completion Date2025-01

Terms related to this study

Additional Relevant MeSH Terms

Breast Cancer