Alisertib for Small Cell Lung Cancer

(ALISCA-Lung1 Trial)

Recruiting at 30 trial locations

Overseen By Puma Biotechnology, Inc. Clinical Operations Senior Director

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Puma Biotechnology, Inc.

Must not be taking: AURKA inhibitors

Disqualifiers: Prior AURKA treatment, 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: 21-day cycles, assessed up to 36 months

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests alisertib, an experimental treatment for small cell lung cancer (SCLC). It targets individuals whose cancer has progressed after both platinum-based chemotherapy and anti-PD-L1 immunotherapy. The trial aims to determine if alisertib slows the disease and identifies specific patient groups who benefit most. Individuals who have undergone up to two prior treatments for SCLC, excluding alisertib or similar drugs, may qualify. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study center to understand any specific requirements.

Is there any evidence suggesting that alisertib is likely to be safe for humans?

Research has shown that alisertib has been tested for safety in patients with various solid tumors, including small cell lung cancer (SCLC). In these studies, about 43% of patients experienced serious side effects related to the drug. Despite this, researchers see potential in further studying the treatment. While alisertib carries some risks, it might benefit certain patients with SCLC. Potential participants should discuss these risks and benefits with their healthcare provider to make an informed decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for small cell lung cancer?

Unlike the standard treatments for small cell lung cancer, which typically involve chemotherapy and immunotherapy, Alisertib offers a fresh approach by targeting a specific enzyme called Aurora A kinase. This enzyme plays a crucial role in cell division, and by inhibiting it, Alisertib aims to prevent cancer cells from multiplying. Researchers are excited about this treatment because it could potentially offer a more targeted attack on cancer cells, possibly resulting in fewer side effects compared to traditional chemotherapy. Additionally, the oral administration of Alisertib makes it a convenient option for patients, potentially improving adherence to treatment.

What evidence suggests that alisertib might be an effective treatment for small cell lung cancer?

Research suggests that alisertib, a new drug under study in this trial, might help treat small cell lung cancer (SCLC). This drug blocks a protein that aids cancer cell division and growth. In earlier research, alisertib demonstrated tumor-fighting capabilities in lab tests, which is encouraging. One study showed a patient with SCLC experienced a partial response, meaning their cancer reduced in size. While these results are promising, ongoing research in this trial is needed to determine which patients might benefit the most. ^{2 3 6 7 8}

Who Is on the Research Team?

Chief Scientific Officer

Principal Investigator

Puma Biotechnology, Inc.

Are You a Good Fit for This Trial?

This trial is for adults over 18 with extensive-stage small cell lung cancer (ES-SCLC) who have already tried platinum-based chemotherapy and an anti-PDL-1 immunotherapy agent but the cancer has progressed. People can't join if they've previously been treated with AURKA or pan-Aurora-targeted agents, including alisertib.

Inclusion Criteria

My cancer is a type of small cell lung cancer confirmed by a lab test.

My cancer progressed after first-line platinum chemotherapy and I've had anti-PDL-1 treatment.

Exclusion Criteria

I have been treated with a drug targeting AURKA or Aurora kinases, like alisertib.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 50 mg of alisertib PO BID on days 1-7 of each 21-day cycle

21-day cycles, assessed up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• Alisertib

Trial Overview The study is testing the effectiveness of a drug called Alisertib in patients whose ES-SCLC has worsened despite initial treatments. It aims to understand how safe Alisertib is, how it affects the body, and which specific patient groups might benefit most from it.

How Is the Trial Designed?

Group I: Alisertib Experimental Treatment 1 Intervention

50 mg (Prior to Amendment 2) or 60 mg (Amendment 2) of alisertib PO BID on days 1-7 of each 21-day cycle

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

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]

Alisertib, a potent Aurora A kinase inhibitor, shows promising anti-cancer effects by improving time to disease progression and progression-free survival in a review of seven studies involving 630 patients.

Despite its efficacy, Alisertib is associated with serious hematological side effects in a significant number of patients, suggesting the need for careful management and consideration of more targeted administration routes to minimize these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical risk-benefit assessment of the novel anti-cancer aurora a kinase inhibitor alisertib (MLN8237): A comprehensive review of the clinical data. Tayyar, Y., Jubair, L., Fallaha, S., et al.[2018]

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 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 study of 178 patients with relapsed or refractory small cell lung cancer (SCLC), the combination of alisertib and paclitaxel showed a median progression-free survival (PFS) of 3.32 months, compared to 2.17 months with placebo and paclitaxel, indicating a potential benefit of the treatment.

Patients with specific genetic alterations in cell cycle regulators experienced significantly improved PFS and overall survival when treated with alisertib/paclitaxel, suggesting that these genetic markers could help predict who will benefit most from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II Study of Paclitaxel plus Alisertib versus Paclitaxel plus Placebo as Second-Line Therapy for SCLC: Primary and Correlative Biomarker Analyses. Owonikoko, TK., Niu, H., Nackaerts, K., et al.[2021]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS8128

Alisertib in patients with extensive-stage small-cell lung ... Alisertib is a highly selective, reversible, ATP-competitive, orally administered, small-molecule AURKA inhibitor under investigation for treating SCLC.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06095505

NCT06095505 | A Study of Alisertib in Patients With ... This study is intended to identify the biomarker-defined subgroup(s) that may benefit most from alisertib treatment and to evaluate the efficacy, safety, and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8259450/

Phase 1 Study of Alisertib (MLN8237) and Weekly ... One partial response in 11 efficacy evaluable patients (9%) occurred in a patient with small cell lung cancer. The study was terminated prior to the planned ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)45041-2/fulltext

Randomized phase 2 study of investigational aurora A ... Alisertib, a selective AAK inhibitor, showed single-agent antitumor activity in preclinical in vivo SCLC models and was synergistic with P in this setting.

5. jto.org jto.org/article/S1556-0864(16)31494-0/fulltext

OA05.05 Randomized Phase 2 Study: Alisertib (MLN8237) ... Alisertib, an investigational selective Aurora A kinase inhibitor, showed single-agent antitumor activity in preclinical in vivo SCLC models and was ...

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

Safety and activity of alisertib, an investigational aurora ... These data support further clinical assessment of alisertib in patients with solid tumours, particularly those with breast cancer and small-cell lung cancer.

8. ascopubs.org ascopubs.org/doi/10.1200/jco.2013.31.15_suppl.605

Updated ph II results in patients (pts) with small cell lung ... Updated safety and efficacy results from phase I/II study of HM61713 in patients (pts) with EGFR mutation positive non-small cell lung cancer ( ...