The purpose of this study is to evaluate how OSI-906 compares to Topotecan in trying to slow down the growth and/or progression of the tumors of participants with relapsed or recurrent Small Cell Lung Cancer. This study also plans to find out what effects, good or bad (side effects), OSI-906 has on participants and or Small Cell Lung Cancer. The study will also investigate if some proteins measured in the blood or tumor and some imaging features obtained from computed tomography (CT) scans can help predict whether OSI-906 or topotecan will be effective against Small Cell Lung Cancer.
PRIMARY OBJECTIVES: I. To compare the progression-free survival (PFS) of single-agent OSI-906 (linsitinib) to that of single-agent topotecan (topotecan hydrochloride) in patients with relapsed small cell lung cancer (SCLC). SECONDARY OBJECTIVES: I. To evaluate the response rate (RR), disease-control rate (DCR) and overall survival (OS) of single-agent OSI-906 in patients with relapsed SCLC. II. To describe the toxicity profile of single-agent OSI-906 in this population. TERTIARY OBJECTIVES: I. To evaluate potential predictive biomarkers of OSI-906 sensitivity. II. To determine whether the baseline insulin-like growth factor (IGF)-1, IGF-binding proteins (BPs), or angiogenic markers (vascular endothelial growth factor \[VEGF\] and interleukin \[IL\]-8) plasma levels or their pre- and post-treatment plasma level changes, significantly differ between progressor and non-progressor patients and correlate them with survival. III. To assess whether the baseline protein kinase B (AKT) and/or mitogen-activated protein kinase 1 (ERK) phosphorylation or the extent of inhibition of AKT and/or ERK phosphorylation in peripheral blood mononuclear cells (PBMCs) significantly differs between progressors and non-progressors and to correlate them with survival. IV. To determine whether the subcellular localization of IGF-1R, IGF-BPs, and/or the phosphorylation of IGF-1R throughout the cell by AQUA (automated quantitative immunofluorescence) significantly differs between progressors and non-progressors and correlate them with survival. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive linsitinib orally (PO) twice daily (BID) on days 1-21. ARM II: Patients receive topotecan hydrochloride intravenously (IV) over 30 minutes or PO once daily (QD) on days 1-5. Patients may crossover to Arm I at the time of progressive disease. In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks and then every 6 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
44
Correlative studies
150 mg given orally (PO) twice a day (BID)
Correlative studies
1.5 mg/m\^2 intravenously (IV) or 2.3 mg/m\^2 orally (PO)
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Moffitt Cancer Center
Tampa, Florida, United States
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital
Baltimore, Maryland, United States
Billings Clinic Cancer Center
Billings, Montana, United States
Case Western Reserve University
Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
...and 1 more locations
Median Progression Free Survival (PFS)
PFS: Time from randomization to time of disease progression or death. PFS summarized with the Kaplan-Meier (K-M) method by two arms (experimental versus control). Confidence intervals for the median PFS and PFS rates at different time points to be constructed when appropriate.
Time frame: Up to 6 months
Disease Control Rate (DCR)
DCR: Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) + Progressive Disease (PD). DCR summarized using both point estimates and exact confidence intervals based on the binomial distribution by arm.
Time frame: Up to 2 years
Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs
Participants with Grade 3 and 4 toxicities, possibly/probably/definitely related to study drugs. Number of Participants is per Event Category. Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Time frame: 1 year, 6 months
Overall Survival (OS)
OS: Time from study enrollment to death from any cause. OS summarized similarly to PFS utilizing the K-M method.
Time frame: Up to 2 years
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