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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04791384
Recruitment Status : Not yet recruiting
First Posted : March 10, 2021
Last Update Posted : March 10, 2021
Information provided by (Responsible Party):
Criterium, Inc.

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Abemaciclib Drug: Elacestrant Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multicenter Open Label Phase Ib/II Trial of Abemaciclib and Elacestrant in Patients With Brain Metastasis Due to HR+/Her2- Breast Cancer
Estimated Study Start Date : May 2021
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Abemaciclib

Arm Intervention/treatment
Experimental: Abemaciclib/Elacestrant
Abemaciclib and Elacestrant combination
Drug: Abemaciclib
taken orally

Drug: Elacestrant
taken orally

Primary Outcome Measures :
  1. The number of patients in Phase 1b part of the study with any adverse events (AE). [ Time Frame: 1.5 years ]
    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.

  2. Assess the efficacy of the drug combination abemaciclib and elacestrant. [ Time Frame: The whole study- 2.5 years ]
    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.

Secondary Outcome Measures :
  1. Evaluate tumor response rates of treatment with abemaciclib and elacestrant combination. [ Time Frame: 2.5 years ]
    Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. tumor responses conducted before patients start treatment, at timepoints while they receive treatment, and when their treatment ends, will be evaluated.

  2. Evaluate duration of tumor response rates of treatment with abemaciclib and elacestrant combination. [ Time Frame: 2.5 years ]
    Duration of intracranial benefit rate will be measured per the response assessment in neuro-oncology brain metastases (RANO-BM) for the time of participation in the study.

  3. The percentage of patients to complete the study. [ Time Frame: 2.5 years ]
    Study participants will be followed for the duration of their participate in the study for overall survival.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion 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).

      Post-menopausal status is defined as:

      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.

      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

      Renal Serum creatinine: </= 1.5 × ULN Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; ULN = upper limit of normal.

    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).

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04791384

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Contact: Kari Anderson 518-583-0095

Sponsors and Collaborators
Criterium, Inc.
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Principal Investigator: Peter Kabos, MD University of Colorado, Denver
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Responsible Party: Criterium, Inc. Identifier: NCT04791384    
Other Study ID Numbers: Lilly-I3Y-US-I026
First Posted: March 10, 2021    Key Record Dates
Last Update Posted: March 10, 2021
Last Verified: March 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Brain Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases