Alisertib + Endocrine Therapy for Breast Cancer

(ALISCA-Breast1 Trial)

Recruiting at 39 trial locations

Overseen By Puma Biotechnology, Inc. Clinical Operations Senior Director

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 48 months

150 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

Is 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. ^{1 2 3 4 6}

What 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. ^{1 2 3 4 7}

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.

Research Team

Chief Reg Affairs, PV, Medical Affairs and Law Officer

Principal Investigator

Puma Biotechnology, Inc.

Eligibility 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.

My breast cancer has returned or spread and cannot be cured with surgery or radiation.

I have been treated with CDK4/6 inhibitors and hormone therapy for my cancer.

Exclusion Criteria

I am receiving chemotherapy for cancer that has returned or spread.

I have been treated with a drug targeting Aurora Kinase A.

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

Treatment Details

Interventions

• Alisertib

Trial Overview 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.

Participant Groups

Group I: Alisertib 50 mg Experimental Treatment 2 Interventions

Alisertib with selected endocrine therapy

Group II: Alisertib 40 mg Experimental Treatment 2 Interventions

Alisertib with selected endocrine therapy

Group III: Alisertib 30 mg Experimental Treatment 2 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

Who Is Running the Clinical Trial?

Puma Biotechnology, Inc.

Lead Sponsor

Trials

58

Recruited

10,100+

Findings from Research

The combination of alisertib (20 mg twice daily) and docetaxel (75 mg/m²) was found to be safe and well-tolerated in a study involving 41 patients with metastatic cancer, with the recommended phase 2 dose established for future research.

Out of 28 patients evaluated for efficacy, 29% showed objective responses, including one complete response in bladder cancer and several partial responses in prostate cancer and angiosarcoma, indicating potential antitumor activity of the combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label, multicenter, phase 1 study of alisertib (MLN8237), an aurora A kinase inhibitor, with docetaxel in patients with solid tumors. Graff, JN., Higano, CS., Hahn, NM., et al.[2018]

In a phase I trial involving 10 postmenopausal patients with endocrine-resistant ER+ metastatic breast cancer, the combination of alisertib and fulvestrant was well tolerated, with no severe toxicities reported during the first treatment cycle.

The treatment showed promising antitumor activity, with a median progression-free survival of 12.4 months and a 6-month clinical benefit rate of 77.8%, indicating potential effectiveness even in patients who had previously progressed on fulvestrant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial to evaluate the addition of alisertib to fulvestrant in women with endocrine-resistant, ER+ metastatic breast cancer. Haddad, TC., D'Assoro, A., Suman, V., et al.[2023]

The phase I study of MLN8237 (alisertib) in 87 adult patients with advanced solid tumors demonstrated that the drug is generally well-tolerated, with common side effects including fatigue, nausea, and neutropenia.

At the maximum tolerated dose of 50 mg twice daily, MLN8237 effectively inhibited Aurora A kinase activity, leading to a partial response in 1% of patients and stable disease in 23% for at least 3 months, suggesting potential efficacy in treating solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of aurora A kinase inhibitor MLN8237 in advanced solid tumors: safety, pharmacokinetics, pharmacodynamics, and bioavailability of two oral formulations. Dees, EC., Cohen, RB., von Mehren, M., et al.[2021]

Alisertib, an investigational cancer treatment, showed a 26% increase in total systemic exposure when administered as an oral solution compared to its powder-in-capsule formulation, indicating better bioavailability.

The oral solution of alisertib was absorbed faster than the capsule form, with a quicker peak concentration reached in the bloodstream, suggesting it may be a more effective option for patients who have difficulty swallowing solid medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative bioavailability of a prototype oral solution of the Aurora A kinase inhibitor alisertib (MLN8237) in patients with advanced solid tumors. Falchook, GS., Venkatakrishnan, K., Sarantopoulos, J., et al.[2015]

High expression of the RET receptor tyrosine kinase in ER-positive breast cancer patients is linked to significantly worse survival outcomes, indicating it may be a critical biomarker for identifying high-risk patients.

Patients with high RET and GDNF expression may benefit from targeted therapies, as their tumors show enrichment for pathways that can be targeted with tyrosine kinase inhibitors, suggesting a potential new treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High expression of the RET receptor tyrosine kinase and its ligand GDNF identifies a high-risk subset of estrogen receptor positive breast cancer. Kakati, RT., Kim, H., Whitman, A., et al.[2023]

The maximum tolerated dose (MTD) of alisertib for East Asian patients with advanced solid tumors or lymphomas was determined to be 30 mg twice daily, which is lower than the 50 mg dose established for Western patients, likely due to higher systemic exposure in this population.

Alisertib was generally well tolerated, with common side effects including neutropenia and stomatitis, and it demonstrated preliminary efficacy, with one patient achieving a partial response and over half of the participants maintaining stable disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in East Asian cancer patients: pharmacokinetics and recommended phase 2 dose. Venkatakrishnan, K., Kim, TM., Lin, CC., et al.[2022]

Alisertib (MLN8237) is a selective inhibitor of Aurora A kinase, showing promise in treating various cancers, including neuroblastoma and small cell lung cancer, based on its role in cell division and potential non-mitotic functions.

The development of alisertib is guided by scientific insights into Aurora A biology, leading to its evaluation in combination with other therapies like taxanes and EGFR inhibitors to enhance its antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scientific Rationale Supporting the Clinical Development Strategy for the Investigational Aurora A Kinase Inhibitor Alisertib in Cancer. Niu, H., Manfredi, M., Ecsedy, JA.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Open-label, multicenter, phase 1 study of alisertib (MLN8237), an aurora A kinase inhibitor, with docetaxel in patients with solid tumors. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Phase I trial to evaluate the addition of alisertib to fulvestrant in women with endocrine-resistant, ER+ metastatic breast cancer. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Phase I study of aurora A kinase inhibitor MLN8237 in advanced solid tumors: safety, pharmacokinetics, pharmacodynamics, and bioavailability of two oral formulations. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Relative bioavailability of a prototype oral solution of the Aurora A kinase inhibitor alisertib (MLN8237) in patients with advanced solid tumors. [2015]

5. Netherlands pubmed.ncbi.nlm.nih.gov

High expression of the RET receptor tyrosine kinase and its ligand GDNF identifies a high-risk subset of estrogen receptor positive breast cancer. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Phase 1 study of the investigational Aurora A kinase inhibitor alisertib (MLN8237) in East Asian cancer patients: pharmacokinetics and recommended phase 2 dose. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Scientific Rationale Supporting the Clinical Development Strategy for the Investigational Aurora A Kinase Inhibitor Alisertib in Cancer. [2023]