A Study of Alisertib and Paclitaxel in Patients With Small Cell Lung Cancer (SCLC)

A Phase 2 Study of Alisertib in Combination With Paclitaxel in Patients With Small Cell Lung Cancer

The goal of this clinical trial is to determine how well people tolerate treatment with alisertib at different doses when it is used together with paclitaxel to treat people with SCLC. The main question it aims to answer is:

• What percentage of side effects, both mild and serious, do participants experience when being treated with alisertib and paclitaxel based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v.5.0)?

The study will consist of different groups, called cohorts, in which alisertib will be studied at increasing doses. Participants in the first group, Cohort 1, will take 30 mg of alisertib by mouth 2 times a day. The dose will increase by 10 mg 2 times a day for each new cohort of participants joining the study. Side effects will be checked during the study, and the decision to increase the dose of alisertib will be based on the specific side effects experienced during the first 21 days of treatment for each cohort.

Participants will:

• take alisertib by mouth on their own 2 times a day from Day 1 through Day 7 of each 21-day cycle and will be given paclitaxel intravenously at a dose of 60 mg/m2 on Day 1 and Day 8 of each 21-day cycle.
• be given a preventive treatment to increase their body defenses, called granulocyte-colony stimulating factor (G-CSF). Study staff will give G-CSF after the last dose of alisertib or paclitaxel of each 21-day cycle in which alisertib was given.
• provide blood samples to evaluate the different levels of alisertib in the blood at different times. Blood samples will be collected on Days 1 and 7 of the first and second 21-day cycles of treatment.
• be treated with alisertib and paclitaxel until death, worsening of the disease, unacceptable toxicity, unwillingness to continue participating in the trial, or other criteria that requires participants to stop treatment and participation in the study.
• be contacted every 8 weeks after stopping alisertib and paclitaxel treatment as part of a specific study phase called the long-term follow-up period. This will last until death, unwillingness to continue participating in the trial, or until the end of the study.

This is a Phase 2 open label study evaluating increasing doses of alisertib administered in combination with paclitaxel in patients with pathologically confirmed small cell lung cancer (SCLC) following progression on or after treatment with up to 2 prior treatment regimens. Patients must have received treatment with platinum-based chemotherapy and an anti-programmed death receptor 1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) immunotherapy agent. Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Starting with alisertib 30 mg twice a day (BID) in Cohort 1 and increasing in each successive cohort by 10 mg BID, each dosing cohort will enroll approximately 10 safety-evaluable patients to assess safety. Toxicity will be assessed throughout the study using NCI CTCAE v5.0, and decisions regarding escalating the alisertib dose will be based on the occurrence of Events during Cycle 1 (Days 1-21) of each dose level. If 3 or fewer patients experience an Event during Cycle 1, then the alisertib dose may be increased by 10 mg BID at the next dose level. It is not anticipated that the planned dosage of alisertib would exceed 70 mg BID. At the time 10 patients have completed Cycle 1 or the maximum number (4) of Events has been reached, whichever is sooner, the Sponsor will hold enrollment until a decision on moving to the next dose level is made.

Inclusion Criteria:

• Aged ≥18 years at signing of informed consent
• Pathologically confirmed SCLC
• Prior treatment with one platinum-based chemotherapy and an anti-PD-1/PD-L1 immunotherapy. Up to one additional systemic anti-cancer therapy for SCLC is allowed, for a total of up to 2 prior treatment regimens
• Measurable disease as defined by RECIST v1.1

Exclusion Criteria:

• Prior treatment with an aurora kinase A (AURKA) specific-targeted or pan-Aurora- targeted agent, including alisertib, in any setting

There are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.