Small Cell Lung Cancer ( SCLC )
Conditions
Keywords
alisertib, SCLC
Brief summary
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.
Detailed description
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.
Interventions
DRUGAlisertib
Alisertib enteric-coated tablets, 30 mg BID self-administered orally on Days 1-7 of every 21-day cycle
DRUGPaclitaxel
60 mg/m\^2 IV on Days 1 and 8 of every 21-day cycle
Sponsors
Puma Biotechnology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with Treatment-Emergent Adverse Events (Adverse Events and Serious Adverse Events) | From date of first dose through last dose plus 28 days, assessed up to 24 months | Treatment emergent adverse events are those events reported on or after the first dose of investigational product and up to 28 days after the last dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From date of first dose to first confirmed Complete or Partial Response, assessed up to 24 months | ORR is defined as the proportion of participants demonstrating a confirmed Complete or Partial Response during the treatment phase of the study. |
| Duration of response (DOR) | From start date of response to first PD or death, assessed up to 24 months | DOR is measured from the time at which measurement criteria are first met for confirmed Complete or Partial Response (whichever status is recorded first) until the first date of recurrence or progressive disease (PD) or death is objectively documented. |
| Disease Control Rate (DCR) | From date of first dose to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 24 months | DCR is defined as the proportion of patients who achieve overall tumor response (confirmed Complete or Partial Response) or Stable Disease lasting for at least 12 weeks from first dose of investigational product. |
| Progression Free Survival (PFS) | From date of first dose to date of recurrence, progression or death, assessed up to 24 months | PFS is measured in months and based on the local tumor assessment. The time interval from the date of first dose until the first date on which recurrence, progression, or death due to any cause, is documented. |
| Overall Survival (OS) | From date of first dose to death, assessed up to 24 months | OS is defined as the time from date of first dose to death due to any cause, censored at the last date known alive on or prior to the data cutoff employed for the analysis, whichever was earlier. |
Countries
Spain
Contacts
CONTACTPuma Biotechnology, Inc. Clinical Operations Senior Director
STUDY_DIRECTORChief Reg Affairs, Med Affairs, Pharmacovigilance Officer
Puma Biotechnology, Inc.
Outcome results
None listed