Linsitinib or Topotecan Hydrochloride in Treating Patients With Relapsed Small Cell Lung Cancer
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.
|Recurrent Small Cell Lung Carcinoma||Other: Laboratory Biomarker Analysis Drug: Linsitinib Other: Pharmacological Study Drug: Topotecan Hydrochloride||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||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)|
- Median Progression Free Survival (PFS) [ Time Frame: Up to 6 months ]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.
- Disease Control Rate (DCR) [ Time Frame: Up to 2 years ]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.
- Incidence of Serious Adverse Events (SAEs) Possibly/Probably Definitely Related to Study Drugs [ Time Frame: 1 year, 6 months ]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.
- Overall Survival (OS) [ Time Frame: Up to 2 years ]OS: Time from study enrollment to death from any cause. OS summarized similarly to PFS utilizing the K-M method.
- Changes in Biomarker Expression [ Time Frame: Baseline to up to day 1 of course 3 ]To be assessed by the Wilcoxon rank sum test.
|Study Start Date:||February 2012|
|Study Completion Date:||November 2014|
|Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm I: OS-906 (linsitinib)
OS-906 daily, continuously, every 3 weeks.
Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Linsitinib
150 mg given orally (PO) twice a day (BID)
Other Names:Other: Pharmacological Study
Active Comparator: Arm II (topotecan hydrochloride)
Patients receive topotecan hydrochloride IV over 30 minutes or PO QD on days 1-5. Patients may crossover to Arm I at the time of progressive disease.
Other: Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacological Study
Correlative studiesDrug: Topotecan Hydrochloride
1.5 mg/m^2 intravenously (IV) or 2.3 mg/m^2 orally (PO)
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).
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01533181
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|United States, Georgia|
|Emory University/Winship Cancer Institute|
|Atlanta, Georgia, United States, 30322|
|United States, Iowa|
|University of Iowa/Holden Comprehensive Cancer Center|
|Iowa City, Iowa, United States, 52242|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21231|
|United States, Montana|
|Billings Clinic Cancer Center|
|Billings, Montana, United States, 59107|
|United States, Ohio|
|Case Western Reserve University|
|Cleveland, Ohio, United States, 44106|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|United States, Tennessee|
|Vanderbilt University/Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Johns Hopkins Singapore|
|Singapore, Singapore, 308433|
|Principal Investigator:||Alberto Chiappori||Moffitt Cancer Center|