Combination treatment of abemaciclib and elacestrant for breast cancer that has spread to the brain

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

This study is testing if a combination of two medications, abemaciclib and elacestrant, can help people with breast cancer that has spread to the brain feel better and improve their treatment outcomes.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 44 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Criterium, Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation
• Locations: 3 sites (Aurora, Colorado and 2 other locations)
• Trial ID: NCT04791384 on ClinicalTrials.gov

What this trial studies

This is a multi-institutional, open-label Phase Ib/II study evaluating the efficacy of abemaciclib combined with elacestrant in patients with HR+/Her2- breast cancer that has metastasized to the brain. Participants may have previously undergone up to two lines of systemic chemotherapy and can have unlimited prior endocrine therapy. The treatment regimen includes abemaciclib at 150 mg twice daily and elacestrant at 400 mg daily, with monitoring for adverse events and potential dose adjustments. The study will assess safety and efficacy based on patient responses after initial accrual.

Who should consider this trial

Good fit: Ideal candidates are post-menopausal women with measurable brain metastasis from HR+/Her2- breast cancer.

Not a fit: Patients with HER2-positive breast cancer or those who are not post-menopausal may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with brain metastases from HR+/Her2- breast cancer.

How similar studies have performed: While this approach is novel in this specific context, previous studies have shown promise with similar combinations in other settings.

Eligibility criteria

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.

Where this trial is running

Aurora, Colorado and 2 other locations

• University of Colorado — Aurora, Colorado, United States (Recruiting)
• Duke Cancer Center — Durham, North Carolina, United States (Recruiting)
• Cancer Care Northwest — Spokane Valley, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Peter Kabos, MD — University of Colorado, Denver
• Study coordinator: Raquel Lopez

Conditions Breast Cancer