Alisertib + Endocrine Therapy for Breast Cancer
(ALISCA-Breast1 Trial)
Recruiting in Palo Alto (17 mi)
+25 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Puma Biotechnology, Inc.
Must be taking: Endocrine therapy
Must not be taking: Chemotherapy, Aurora Kinase inhibitors
Disqualifiers: Chemotherapy, Aurora Kinase inhibitors, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?PUMA-ALI-1201 is a randomized, dose optimization, multicenter, Phase 2 study of alisertib administered in combination with endocrine therapy in participants with pathology-confirmed HR-positive/HER2-negative metastatic breast cancer (MBC) following progression on or after at least two prior lines of endocrine therapy in the recurrent or metastatic setting. This study is intended to evaluate the optimal alisertib dose administered in combination with the selected endocrine therapy. The study is also planned to evaluate the efficacy, safety, and pharmacokinetics of alisertib in combination with endocrine and to identify the biomarker-defined subgroup(s) that may benefit most from combined alisertib and endocrine therapy.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants must have progressed on at least two prior lines of endocrine therapy, suggesting that you may need to continue with some form of endocrine therapy. Please consult with the study center for specific guidance.
What data supports the effectiveness of the drug Alisertib (MLN8237) when used with endocrine therapy for breast cancer?
In studies, Alisertib, which targets a protein called Aurora A kinase, has shown anti-tumor activity in patients with advanced solid tumors. Additionally, combining Alisertib with fulvestrant, a type of endocrine therapy, has been explored for its potential to overcome resistance in estrogen receptor-positive breast cancer.
12345Is alisertib (MLN8237) safe for humans?
Alisertib has been tested in several studies for safety in humans with different types of cancer. These studies found that it is generally safe, but like many cancer treatments, it can have side effects, which vary depending on the individual and the specific combination of drugs used.
12346What makes the drug Alisertib unique for treating breast cancer?
Alisertib is unique because it is an oral drug that specifically inhibits Aurora A kinase, a protein involved in cell division, which is linked to resistance in estrogen receptor-positive breast cancer. This makes it a novel option when combined with endocrine therapy for patients who have developed resistance to standard treatments.
12347Eligibility Criteria
This trial is for individuals with HR-positive/HER2-negative metastatic breast cancer who have already tried at least two endocrine therapy lines without success. Participants must have confirmed pathology reports and can't join if they've had certain treatments or conditions that the study details exclude.Inclusion Criteria
My cancer progressed after at least 2 hormone treatments in the advanced stage.
I am 18 years old or older.
My breast cancer has returned or spread and cannot be cured with surgery or radiation.
+2 more
Exclusion Criteria
I am receiving chemotherapy for cancer that has returned or spread.
I have been treated with a drug targeting Aurora Kinase A.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive alisertib in combination with endocrine therapy to evaluate optimal dosing and efficacy
48 months
Regular visits as per protocol
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The PUMA-ALI-1201 study tests different doses of Alisertib combined with standard endocrine therapy to find the best dose and assess its effectiveness, safety, and how it's processed in the body. It also aims to identify specific patient subgroups most likely to benefit from this combination treatment.
3Treatment groups
Experimental Treatment
Group I: Alisertib 50 mgExperimental Treatment2 Interventions
Alisertib with selected endocrine therapy
Group II: Alisertib 40 mgExperimental Treatment2 Interventions
Alisertib with selected endocrine therapy
Group III: Alisertib 30 mgExperimental Treatment2 Interventions
Alisertib with selected endocrine therapy
Alisertib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Alisertib for:
- Acute myeloid leukemia (AML)
🇪🇺 Approved in European Union as Alisertib for:
- None approved; under investigation for various cancers
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cancer Specialists of North FloridaJacksonville, FL
UNC Hospitals, University of North Carolina at Chapel HillChapel Hill, NC
Taylor Cancer Research CenterMaumee, OH
University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer CenterSan Francisco, CA
More Trial Locations
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Who Is Running the Clinical Trial?
Puma Biotechnology, Inc.Lead Sponsor
References
Open-label, multicenter, phase 1 study of alisertib (MLN8237), an aurora A kinase inhibitor, with docetaxel in patients with solid tumors. [2018]This study was designed to determine the safety, tolerability, and pharmacokinetics (PK) of alisertib (MLN8237) in combination with docetaxel and to identify a recommended dose for the combination.
Phase I trial to evaluate the addition of alisertib to fulvestrant in women with endocrine-resistant, ER+ metastatic breast cancer. [2023]In estrogen receptor-positive (ER+) breast cancer models, activation of Aurora A kinase (AURKA) is associated with downregulation of ERα expression and resistance to endocrine therapy. Alisertib is an oral selective inhibitor of AURKA. The primary objectives of this phase I trial were to determine the recommended phase II dose (RP2D) and evaluate the toxicities and clinical activity of alisertib combined with fulvestrant in patients with ER+ metastatic breast cancer (MBC).
Phase I study of aurora A kinase inhibitor MLN8237 in advanced solid tumors: safety, pharmacokinetics, pharmacodynamics, and bioavailability of two oral formulations. [2021]This phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of the investigational oral drug MLN8237 (alisertib), a small-molecule Aurora A kinase (AAK) inhibitor, in 87 adult patients with advanced solid tumors.
Relative bioavailability of a prototype oral solution of the Aurora A kinase inhibitor alisertib (MLN8237) in patients with advanced solid tumors. [2015]Alisertib (MLN8237) is an investigational, oral, small-molecule, selective inhibitor of Aurora A kinase. Phase I/II studies of powder-in-capsule (PIC) and enteric-coated tablet formulations of alisertib have determined the recommended phase II dose and have demonstrated anti-tumor activity. This phase I relative bioavailability study characterized the pharmacokinetics of a prototype oral solution (OS) of alisertib (developed for patients unable to swallow solid dosage forms) in reference to the PIC formulation in adult cancer patients.
High expression of the RET receptor tyrosine kinase and its ligand GDNF identifies a high-risk subset of estrogen receptor positive breast cancer. [2023]Resistance to endocrine therapy is the primary cause of treatment failure and death in patients with ER-positive (ER +)/luminal breast cancer. Expression and activation of the RET receptor tyrosine kinase may be driving poor outcomes. We aim to identify high-risk patients and druggable pathways for biomarker-based clinical trials.
Phase 1 study of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in East Asian cancer patients: pharmacokinetics and recommended phase 2 dose. [2022]This phase 1 study assessed the pharmacokinetics (PK), maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), safety, and preliminary efficacy of the investigational Aurora A kinase inhibitor, alisertib, in East Asian patients with advanced solid tumors or lymphomas.
Scientific Rationale Supporting the Clinical Development Strategy for the Investigational Aurora A Kinase Inhibitor Alisertib in Cancer. [2023]Alisertib (MLN8237) is a selective small molecule inhibitor of Aurora A kinase that is being developed in multiple cancer indications as a single agent and in combination with other therapies. A significant amount of research has elucidated a role for Aurora A in orchestrating numerous activities of cells transiting through mitosis and has begun to shed light on potential non-mitotic roles for Aurora A as well. These biological insights laid the foundation for multiple clinical trials evaluating the antitumor activity of alisertib in both solid cancers and heme-lymphatic malignancies. Several key facets of Aurora A biology as well as empirical data collected in experimental systems and early clinical trials have directed the development of alisertib toward certain cancer types, including neuroblastoma, small cell lung cancer, neuroendocrine prostate cancer, atypical teratoid/rhabdoid tumors, and breast cancer among others. In addition, these scientific insights provided the rationale for combining alisertib with other therapies, including microtubule perturbing agents, such as taxanes, EGFR inhibitors, hormonal therapies, platinums, and HDAC inhibitors among others. Here, we link the key aspects of the current clinical development of alisertib to the originating scientific rationale and provide an overview of the alisertib clinical experience to date.