Abemaciclib + SRS for Breast Cancer Brain Metastases
Recruiting in Palo Alto (17 mi)
Overseen ByKamran A Ahmed, MD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Must be taking:Endocrine therapy
Must not be taking: Abemaciclib
Disqualifiers: Leptomeningeal disease, Whole brain radiation, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This is a single arm study of abemaciclib and endocrine therapy with stereotactic radiosurgery (SRS) among patients with hormone receptor (HR)+/HER2- metastatic breast cancer brain metastases.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.
What data supports the effectiveness of the drug Abemaciclib for treating breast cancer brain metastases?
Research shows that Abemaciclib, when combined with endocrine therapy, significantly improves progression-free survival in patients with advanced hormone receptor-positive, HER2-negative breast cancer. This suggests it may be effective in managing breast cancer brain metastases as well.
12345Is Abemaciclib safe for use in humans?
Abemaciclib, when used in combination with endocrine therapy for breast cancer, has shown a tolerable safety profile in clinical trials. Common side effects include diarrhea, infections, and neutropenia (low white blood cell count), but these are generally manageable.
12346What makes the drug Abemaciclib unique for treating breast cancer brain metastases?
Abemaciclib is unique because it is a CDK4/6 inhibitor that, when combined with endocrine therapy, has shown effectiveness in treating hormone receptor-positive breast cancer with brain metastases, a condition that typically has a poor prognosis and limited treatment options. This combination has demonstrated the ability to achieve partial remission in brain metastases, offering a novel approach compared to traditional therapies.
12378Eligibility Criteria
This trial is for individuals with HR+/HER2- metastatic breast cancer brain metastases. Participants can have had prior radiation treatments if there's measurable disease not previously treated with radiation. They must be able to undergo stereotactic radiosurgery, have ≤ 15 brain lesions eligible for this treatment, and a performance status of 0 to 2. Women must test negative for pregnancy and agree to use contraception.Inclusion Criteria
I can take care of myself and am up and about more than half of my waking hours.
I have a brain tumor or cavity from surgery that can be measured and is at least 0.5 cm big.
I can provide a tissue sample from my tumor for testing.
I am a candidate for targeted radiation to my brain or the area where my brain tumor was removed.
I have 15 or fewer brain tumors suitable for targeted radiation.
My breast cancer is hormone receptor positive.
I can take pills by mouth.
My breast cancer is not HER2 positive.
My largest brain tumor is 4 cm or smaller.
Exclusion Criteria
I am not pregnant or breastfeeding.
I have had fainting spells, irregular heartbeats, or sudden cardiac arrest due to heart issues.
I am not allergic to any of the drugs or their components used in this study.
My cancer has spread to the lining of my brain and spinal cord.
I have received whole brain radiation therapy before.
I have not taken abemaciclib for brain metastases or in the past 6 months for metastatic disease.
I do not have any active infections.
Participant Groups
The study tests the combination of abemaciclib and endocrine therapy alongside stereotactic radiosurgery (SRS) in patients with specific breast cancer that has spread to the brain. It's a single-arm study, meaning all participants receive the same treatment without comparison groups.
2Treatment groups
Experimental Treatment
Group I: Phase 2: Radiation Therapy and AbemaciclibExperimental Treatment3 Interventions
Treatment will be initiated with one week of abemaciclib followed by stereotactic radiation at the phase 1 dose to sites of brain metastases or post-operative cavities with continued abemaciclib.
Group II: Phase 1: Radiation Therapy and AbemaciclibExperimental Treatment3 Interventions
Treatment will be initiated with one week of abemaciclib followed by stereotactic radiation to sites of brain metastases or post-operative cavities with continued abemaciclib. In the phase I portion, safety will be monitored initially by a 3+3 design. If unexpected neurologic toxicities are noted, the dose of radiation therapy will be modified.
Abemaciclib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Verzenio for:
- Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
- HR+, HER2- node-positive early breast cancer
🇪🇺 Approved in European Union as Verzenio for:
- HR+, HER2- advanced or metastatic breast cancer
- HR+, HER2- node-positive early breast cancer
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
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Who is running the clinical trial?
H. Lee Moffitt Cancer Center and Research InstituteLead Sponsor
Eli Lilly and CompanyIndustry Sponsor
References
First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]Interim data from the MONARCH3 study indicate that abemaciclib is an effective first-line therapy for advanced ER-positive, HER2-negative breast cancer. Adding the investigational CDK4/6 inhibitor to letrozole significantly improved patients' progression-free survival, compared with those given a placebo alongside endocrine therapy.
Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]Abemaciclib [Verzenio® (USA) or Verzenios® (EU)] is a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor approved in combination with adjuvant endocrine therapy for patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), node-positive, early breast cancer with a high risk of recurrence. In a phase III trial, abemaciclib plus endocrine therapy reduced the risk of recurrence of breast cancer compared with endocrine therapy alone, including in patients who had previously received neoadjuvant chemotherapy, in patients with high- and low-scoring Ki-67 tumours, and in both premenopausal and postmenopausal patients. The tolerability profile of abemaciclib plus endocrine therapy was acceptable and manageable, with diarrhoea, infections and neutropenia being the most common adverse events. Thus, abemaciclib in combination with standard endocrine therapy is a valuable additional treatment option for patients with HR+, HER2-, node-positive early breast cancer with a high risk of recurrence.
Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials. [2022]Abemaciclib in combination with endocrine therapy (ET) has demonstrated significant efficacy benefits in HR+ , HER2- advanced breast cancer patients in the Phase 3 studies MONARCH 2 (fulvestrant as ET) and MONARCH 3 (letrozole or anastrozole as ET). Here, we report age-specific safety and efficacy outcomes.
MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. [2022]Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events. Results Median progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P = .000021; median: not reached in the abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59% in the abemaciclib arm and 44% in the placebo arm ( P = .004). In the abemaciclib arm, diarrhea was the most frequent adverse effect (81.3%) but was mainly grade 1 (44.6%). Comparing abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were neutropenia (21.1% v 1.2%), diarrhea (9.5% v 1.2%), and leukopenia (7.6% v 0.6%). Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.
MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. [2022]Purpose MONARCH 2 ( ClinicalTrials.gov identifier: NCT02107703) compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, plus fulvestrant with fulvestrant alone in patients with advanced breast cancer (ABC). Patients and Methods MONARCH 2 was a global, double-blind, phase III study of women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who had progressed while receiving neoadjuvant or adjuvant endocrine therapy (ET), ≤ 12 months from the end of adjuvant ET, or while receiving first-line ET for metastatic disease. Patients were randomly assigned 2:1 to receive abemaciclib or placebo (150 mg twice daily) on a continuous schedule and fulvestrant (500 mg, per label). The primary end point was investigator-assessed progression-free survival (PFS), and key secondary end points included overall survival, objective response rate (ORR), duration of response, clinical benefit rate, quality of life, and safety. Results Between August 2014 and December 2015, 669 patients were randomly assigned to receive abemaciclib plus fulvestrant (n = 446) or placebo plus fulvestrant (n = 223). Abemaciclib plus fulvestrant significantly extended PFS versus fulvestrant alone (median, 16.4 v 9.3 months; hazard ratio, 0.553; 95% CI, 0.449 to 0.681; P
Abemaciclib: First Global Approval. [2019]Abemaciclib (Verzenio™) is an orally administered inhibitor of cyclin-dependent kinases 4 and 6 that is being developed by Eli Lilly and Company. Abemaciclib has been approved in the USA for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer, in combination with fulvestrant in women with disease progression following endocrine therapy, and as monotherapy in adult patients with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting. In addition, abemaciclib is in various stages of development internationally for a variety of cancers. This article summarizes the milestones in the development of abemaciclib leading to its first approval for the treatment of patients with HR-positive, HER2-negative advanced or metastatic breast cancer.
Abemaciclib plus fulvestrant for the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer with cystic brain metastases: A case report and literature review. [2022]Cystic brain metastases (CBM) in patients with breast cancer are rare. They have a worse prognosis than solid brain metastases, and they are less sensitive to radiotherapy. We report a case of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer with CBM. The patient underwent treatment with docetaxel combined with capecitabine for 5 months, followed by anastrozole maintenance therapy for 10 months, and palbociclib combined with exemestane for 22 months. CBM emerged and bone metastases increased in number. A missense mutation in PIK3CA (exon 10, c.1633G>A [p.Glu545Lys]) was detected by whole-exome next-generation sequencing from peripheral blood samples. After whole-brain radiotherapy (40 Gy/20 fx) combined with 3 months of treatment with everolimus and fulvestrant, CBM demonstrated partial remission (PR), but extracranial bone metastases continued to increase in number. Thus, the patient underwent fourth-line treatment with abemaciclib (100 mg bid) combined with fulvestrant (500 mg). Three months later, CBM significantly demonstrated PR and extracranial bone metastases were stable. At present, the patient has above 9 months of progression-free survival time without obvious adverse effects. This is the first report of abemaciclib combined with fulvestrant in the treatment of CBM in a patient with HR+/HER2- breast cancer.
A Phase II Study of Abemaciclib in Patients with Brain Metastases Secondary to Hormone Receptor-Positive Breast Cancer. [2021]Label="PURPOSE">The primary objective was to evaluate intracranial objective response rate (iORR) in patients receiving abemaciclib with brain or leptomeningeal metastases (LM) secondary to hormone receptor-positive (HR+) metastatic breast cancer (MBC). Secondary objectives evaluated extracranial response, abemaciclib pharmacokinetics, brain metastases tissue exposure, and safety.