IRB Study Number 23-1000
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objective
Determine whether any biomarker correlates with alisertib response
Secondary Objectives
Determine investigator-assessed efficacy in the patient population
Determine survival outcomes in the patient population
Determine the safety profile of alisertib
Update the population pharmacokinetic (popPK) profile of alisertib
Inclusion Criteria
Provide written, informed consent to participate in the study and follow the study procedures.
Aged ≥18 years at signing of informed consent.
Pathologically confirmed ES-SCLC. Note: SCLC must be the primary diagnosis; mixed SCLC is allowed. Patients with transformed SCLC are not eligible.
Progression on or after first-line platinum-based chemotherapy. Patients must have also received a prior anti-PDL-1 immunotherapy agent.
At least one measurable target lesion outside of the central nervous system (CNS) as defined by RECIST v1.1.
Must provide most recent formalin fixed paraffin embedded (FFPE) tissue biopsy. Archival tissue is acceptable; if archival tissue is unavailable, patient must be willing to provide fresh tissue biopsy.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Elapsed time from prior indication-based therapy to C1D1:
a. ≥21 days or 5 half-life periods (whichever is shorter) from last dose of prior systemic therapy. There must be a minimum of 7 days between the last dose of prior systemic therapy and C1D1.
b. ≥14 days from previous radiation therapy.
Negative serum β-human chorionic gonadotropin (hCG) pregnancy test for premenopausal women of childbearing potential (those who are biologically capable of having children) and for women less than 12 months after menopause.
Patients requiring full systemic anticoagulation must have been on a stable dose and schedule for more than 1 month prior to C1D1.
Female patients of childbearing potential must agree and commit to the use of a highly effective method of contraception from the time of informed consent until 28 days after the last dose of the study treatment. If 1 of the highly effective methods cannot be used, using 2 other effective methods at the same time is required. Male patients must agree and commit to using a highly effective method of contraception while on treatment and for 3 months after last dose of study treatment. Male patients must refrain from donating sperm during the trial and for 3 months after last dose of study treatment.
a. Highly effective methods: Intra-uterine (IUD) devices, hormonal (birth control pills/oral contraceptives, injectable contraceptives, contraceptive patches, or contraceptive implants)
b. Other effective methods (barrier methods): Latex condom, diaphragm with spermicide, cervical cap, sponge
- Adequate major organ and hematologic function as defined by the screening parameters below: (See protocol)
Exclusion Criteria
Major surgery within 21 days of C1D1 (major according to the Investigator’s and/or Medical Monitor’s assessment).
Prior treatment with an AURKA specific-targeted or pan-Aurora-targeted agent, including alisertib in any setting.
Grade ≥3 dyspnea or dependence on daily intermittent oxygen within 14 days of C1D1.
Any active infection requiring systemic treatment (antibacterial, antiviral, or antifungal) within 7 days of C1D1.
Immunocompromised patients, including:
a. Known active HIV infection as determined by HIV RNA viral load and CD4 count.
b. Known active or uncontrolled hepatitis B or C infection as determined by positive hepatitis B tests (HBs and anti-HBc) or hepatitis C test (HCV antibody).
Known upcoming need for radiation therapy.
Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association [NYHA] functional classification of ≥2), unstable angina, myocardial infarction or ventricular arrhythmia within 12 months of C1D1.
Mean resting corrected QTcF interval >470 milliseconds or known history of congenital QT-prolongation or Torsade de Pointes.
Left ventricular ejection fraction (LVEF) <50% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA).
History of malignancy other than the one to be studied within the past 2 years with the exception of appropriately treated non-invasive malignancies (e.g., non-melanoma skin cancers, in situ carcinoma of the uterine cervix), unless the patient has been treated with curative intent with no evidence of disease for at least 2 years.
Unresolved Grade >1 toxicities from previous systemic anti-cancer therapy, defined as toxicities not yet improved to National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events Version 5.0 [CTCAE v.5.0] Grade ≤1 or baseline, prior to C1D1, except for any Grade alopecia and Grade 2 neuropathy, Grade 2 fatigue, and residual toxicities from prior immunotherapy, including endocrinopathies adequately controlled by replacement therapy.
CNS metastases. Note: Patients with stable, treated brain metastases are eligible if there is no evidence of progression or hemorrhage and are asymptomatic for at least 14 days prior to C1D1. The patient must be off steroids for at least 14 days prior to C1D1. Patients may remain on a stable dose of anti-convulsants
Currently pregnant or breast-feeding.
Significant chronic GI disorder that can impair the absorption of orally administered drugs (e.g., Crohn’s disease, malabsorption, or Grade ≥ 2 NCI CTCAE v.5.0 diarrhea of any etiology at baseline).
Any use of a proton pump inhibitor (PPI) or H2 receptor antagonists within 5 days prior to C1D1.
Treatment with moderate to strong CYP3A4 inducers (e.g., phenytoin, rifampin) and inhibitors (e.g., ketoconazole) within 14 days prior to C1D1 and during study conduct (see Appendix 3).
Known hypersensitivity to any component of the study treatment or compounds of similar chemical composition.
Any condition that, in the Investigator’s and/or Medical Monitor’s judgment, makes the patient an unreliable trial patient, unlikely to complete the trial, and/or unable to comply with the protocol procedures.
Unable or unwilling to swallow tablets.
