Randomized Phase II Study of Single Agent OSI-906, an Oral, Small Molecule, Tyrosine Kinase Inhibitor (TKI) of the Insulin Growth Factor-1 Receptor (IGF-1R) Versus Topotecan for the Treatment of Patients With Relapsed Small Cell Lung Cancer (SCLC)
I. To compare the progression-free survival (PFS) of single-agent linsitinib (OSI-906) to
that of single-agent topotecan hydrochloride (topotecan) in patients with relapsed small
cell lung cancer (SCLC).
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 using Response Evaluation Criteria in
Solid Tumors (RECIST) v 1.1.
II. To describe the toxicity profile of single-agent OSI-906 in this population using the
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
III. To evaluate potential predictive biomarkers of OSI-906 sensitivity by examining
multiple biomarkers (molecular and radiographic) and to correlate their pre- and
post-treatment samples with clinical outcomes (RR, DCR, PFS, and OS). (Exploratory) IV. To
determine whether the baseline IGF-1, IGF-BP's, or angiogenic markers (VEGF and 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. (Exploratory) V. To
assess whether the baseline AKT and/or ERK phosphorylation or the extent of inhibition of
AKT and/or ERK phosphorylation in peripheral blood mononuclear cells (PBMC) significantly
differs between progressors and non-progressors and to correlate them with survival.
(Exploratory) VI. 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. (Exploratory)
OUTLINE: This is a multicenter study. Patients are stratified according to response to prior
first-line platinum therapy (platinum sensitive vs platinum resistant) and ECOG performance
status (0-1 vs 2). 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 IV over 30 minutes or PO once daily (QD) on
days 1-5.* NOTE: *Patients treated on arm II may crossover to arm I at the time of
In both arms, courses repeat every 21 days in the absence of disease progression or
unacceptable toxicity. Patients undergo blood sample collection at baseline, at 6 weeks of
treatment, and at the time of disease progression for IGF-1, IGF-BP's, VEGF, IL-8, Akt,
and/or ERK phosphorylation analysis by ELISA and AQUA. Patients undergo enhanced thoracic
computed tomography scans at baseline, at 6 weeks of treatment, and at the time of
progression for radiomic analysis.
After completion of study treatment, patients are followed up for 4 weeks and then every 6
months for 2 years.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
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 will be constructed when appropriate.
Time from the time of randomization to time of disease progression or death, up to 18 weeks
H. Lee Moffitt Cancer Center and Research Institute
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|
|University of Wisconsin Hospital and Clinics||Madison, Wisconsin 53792-0001|
|Mayo Clinic in Arizona||Scottsdale, Arizona 85259-5404|
|Vanderbilt University||Nashville, Tennessee 37232-6305|
|University of North Carolina||Chapel Hill, North Carolina 27599|
|Case Western Reserve University||Cleveland, Ohio 44106|
|Emory University||Atlanta, Georgia 30322|
|Ohio State University Medical Center||Columbus, Ohio 43210|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|Billings Clinic||Billings, Montana 59107-7000|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital||Baltimore, Maryland 21231|