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

Plain English Summary

Phase Ib/II Trial of Abemaciclib and Elacestrant in Patients With Brain Metastasis Due to HR+/Her2- Breast Cancer is a Phase 2 clinical trial sponsored by Criterium, Inc. studying Breast Cancer. This trial tests a combination of two drugs, abemaciclib and elacestrant, to see how well they work and if they are safe for patients with breast cancer that has spread to the brain. It is for post-menopausal women with a specific type of breast cancer (HR+/Her2-) that has spread to the brain and may have progressed after previous treatments. Participation involves taking oral medications and attending regular study visits for assessments. The trial is open-label, meaning both patients and doctors know which treatment is being given. Alternatives may include other cancer treatments, palliative care, or clinical trials investigating different therapies. The trial aims to enroll 5 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Women who are post-menopausal and have been diagnosed with HR+/Her2- breast cancer that has spread to the brain. Patients must have measurable brain tumors and may have had up to two prior chemotherapy treatments for metastatic disease. Individuals with certain serious pre-existing medical conditions, or those who are pregnant or breastfeeding, cannot participate. Patients must have adequate organ function (blood counts, liver, and kidney function) and be able to take oral medications. This trial is studying Breast Cancer, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures will assess the safety of the drug combination by tracking any side effects experienced by patients and evaluate how well the combination treatment controls or shrinks tum The specific primary outcome measures are: The number of patients in Phase 1b part of the study with any adverse events (AE). (1.5 years); Assess the efficacy of the drug combination abemaciclib and elacestrant. (The whole study- 2.5 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for effective treatments for breast cancer that has spread to the brain, a common and challenging complication of the disease. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial investigates a novel combination therapy for a difficult-to-treat subset of breast cancer patients, potentially opening new treatment avenues and representing a significant market opportuni Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of abemaciclib and elacestrant, and how this trial fits with other treatment options. Be prepared for regular clinic visits for blood tests, scans, and to report any side effects or changes in your health. You will need to take the study medications by mouth as directed and use effective birth control if you are of childbearing potential. The trial is being conducted at 4 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 5 participants

Interventions

• DRUG: Abemaciclib — taken orally
• DRUG: Elacestrant — taken orally

Primary Outcomes

• The number of patients in Phase 1b part of the study with any adverse events (AE). (1.5 years)
• Assess the efficacy of the drug combination abemaciclib and elacestrant. (The whole study- 2.5 years)

Secondary Outcomes

• Evaluate tumor response rates of treatment with abemaciclib and elacestrant combination. (2.5 years)
• Evaluate duration of tumor response rates of treatment with abemaciclib and elacestrant combination. (2.5 years)
• The percentage of patients to complete the study. (2.5 years)

Full 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

Trial Locations

• University of Colorado, Aurora, Colorado, United States
• Mount Sinai Comprehensive Cancer Center, Miami Beach, Florida, United States
• Duke Cancer Center, Durham, North Carolina, United States
• Cancer Care Northwest, Spokane Valley, Washington, United States

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Metastatic Breast Cancer
• Hormone Receptor-Positive Breast Cancer
• HER2-Negative Breast Cancer
• Brain Metastasis
• Cancer Treatment
• Oncology
• Endocrine Therapy
• Targeted Therapy
• Clinical Trials

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