Alisertib + Endocrine Therapy for Breast Cancer

(ALISCA-Breast1 Trial)

Recruiting at 56 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of alisertib (also known as MLN8237) combined with endocrine therapy for a specific type of breast cancer. It targets individuals with HR-positive/HER2-negative metastatic breast cancer that has worsened after at least two hormonal treatments. The trial aims to determine the optimal dose of alisertib and assess its effectiveness and safety. It also seeks to identify which patient groups might benefit most from this combination treatment. Candidates may qualify if their breast cancer has spread and worsened after at least two hormone-based treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous research has generally shown that alisertib is well-tolerated, with most people not experiencing severe problems. It is often used to treat certain types of cancer. However, some patients experienced serious side effects, occurring in about 43% of participants in some studies. The most common side effects were cytopenias, which involve lower blood cell counts. Despite these issues, researchers continue to study the treatment due to its potential benefits.

This trial is in Phase 2, indicating that alisertib has already been tested in people. At this stage, the goal is to determine the best dose while ensuring safety and effectiveness. Although risks exist, the treatment has shown promise, especially for those who haven't responded to other treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about Alisertib for breast cancer because it targets a unique mechanism compared to standard treatments like hormone therapies or chemotherapy. Alisertib works by inhibiting Aurora A kinase, a protein that plays a critical role in cell division. This action can potentially halt the rapid growth of cancer cells more effectively. Additionally, the trial is exploring different dosages of Alisertib combined with endocrine therapy, which could lead to more personalized and effective treatment strategies for patients.

What evidence suggests that this trial's treatments could be effective for metastatic breast cancer?

Research has shown that alisertib, when combined with hormone therapy, yields promising results for treating HR-positive/HER2-negative metastatic breast cancer. In one study, 41.3% of patients who received alisertib experienced positive effects over six months, known as the 24-week clinical benefit rate. Patients lived an average of 5.6 months without their cancer worsening. Another study found that 61% of patients had stable disease, meaning their cancer did not progress. These findings suggest that alisertib, along with hormone therapy, may help manage this type of breast cancer. Participants in this trial will receive different dosages of alisertib combined with selected endocrine therapy to further evaluate its effectiveness. ^{3 6 7 8 9}

Who Is on the Research Team?

Chief Reg Affairs, PV, Medical Affairs and Law Officer

Principal Investigator

Puma Biotechnology, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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, 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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36892847/

The Phase 2 TBCRC041 Randomized Clinical Trial - PubMed In arm 1, the 24-week clinical benefit rate and median progression-free survival time were 41.3% (90% CI, 29.0%-54.5%) and 5.6 months (95% CI, ...

2. onclive.com onclive.com/view/alisertib-induces-early-signals-of-efficacy-in-endocrine-resistant-breast-cancer

Alisertib Induces Early Signals of Efficacy in Endocrine ... We saw a 19.6% ORR and a 24-week clinical benefit rate [CBR] of 41.3% for the patients who received alisertibmonotherapy. The median progression ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.3589

Phase I study of the combination of alisertib (MLN8237) ... Fourteen of 23 evaluable pts (61%) had stable disease and 2 pts (9%) had partial response (PR) as best overall response. Median PFS was 2.9 ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)52306-7/fulltext

Randomized Phase 2 Study of Investigational, Selective ... Aim: Alisertib has shown modest single-agent activity in platinum-resistant OC and enhanced cytotoxicity with paclitaxel (P) preclinically. A phase 1 study ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4589445/

Inhibition of the Aurora A kinase augments the anti-tumor ... Alisertib enhanced MV oncolysis in vitro and significantly improved outcome in vivo against breast cancer xenografts. In a disseminated MDA-231-lu-P4 lung ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25728526/

Safety and activity of alisertib, an investigational aurora kinase ... Serious drug-related adverse events were reported in 108 (43%) patients. Interpretation: These data support further clinical assessment of alisertib in patients ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01091428

Alisertib (MLN8237) in Participants With Ovarian, Fallopian ... Alisertib was tested to treat people who have ovarian and breast cancer. This study looked at safety, any anti-tumor effect, and it also determined a ...

8. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70051-3/supplemental

Safety and activity of alisertib, an investigational aurora ... Serious drug-related adverse events were reported in 108 (43%) patients. Interpretation. These data support further clinical assessment of alisertib in patients ...

9. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2802267

Evaluation of Alisertib Alone or Combined With Fulvestrant ... Alisertib, a selective AURKA inhibitor, upregulates ERα and restores endocrine sensitivity in preclinical metastatic breast cancer (MBC) models.