Linsitinib or Topotecan Hydrochloride in Treating Patients With Relapsed Small Cell Lung Cancer
This randomized phase II trial studies how well linsitinib works compared to topotecan hydrochloride in treating patients with relapsed small cell lung cancer. Linsitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether linsitinib is more effective than topotecan hydrochloride in treating small cell lung cancer
Combined Type Small Cell Lung Cancer
Fusiform Type Small Cell Lung Cancer
Lymphocyte-like Type Small Cell Lung Cancer
Polygonal Type Small Cell Lung Cancer
Recurrent Small Cell Lung Cancer
Drug: topotecan hydrochloride
Other: laboratory biomarker analysis
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, 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)|
- Progression-free survival [ Time Frame: Time from the time of randomization to time of disease progression or death, up to 18 weeks ] [ Designated as safety issue: No ]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.
- Response rate (RR) as assessed by RECIST v 1.1 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Summarized using both point estimates and exact confidence intervals based on the binomial distribution by arm. Each patient will be assigned one of the following categories: 1) complete response, 2) partial response, 3) stable disease, 4) progressive disease, 5) early death from malignant disease, 6) early death from toxicity, 7) early death because of other cause, or 9) unknown (not assessable, insufficient data).
- Disease-control rate (DCR) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Summarized using both point estimates and exact confidence intervals based on the binomial distribution by arm.
- Overall response rate (RR, DCR, and overall survival [OS]) as assessed by the RECIST v1.1 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Summarized using both point estimates and exact confidence intervals based on the binomial distribution by arm.
- Incidence of toxicities as assessed by NCI CTCAE v.4.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]Simple descriptive statistics will be utilized.
|Study Start Date:||February 2012|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm I (linsitinib)
Patients receive linsitinib PO BID on days 1-21.
Other Name: OSI-906Other: laboratory biomarker analysis
Active Comparator: Arm II (topotecan hydrochloride)
Patients receive topotecan hydrochloride IV over 30 minutes or PO QD on days 1-5.
Drug: topotecan hydrochloride
Given IV or PO
Other Names:Other: laboratory biomarker analysis
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) v.4.0.
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 progressive disease.
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.
|United States, Arizona|
|Mayo Clinic in Arizona||Recruiting|
|Scottsdale, Arizona, United States, 85259|
|Contact: Helen J. Ross 480-301-8335 email@example.com|
|Principal Investigator: Helen J. Ross|
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute||Recruiting|
|Tampa, Florida, United States, 33612|
|Contact: Alberto A. Chiappori 813-745-3050 firstname.lastname@example.org|
|Principal Investigator: Alberto A. Chiappori|
|United States, Georgia|
|Atlanta, Georgia, United States, 30322|
|Contact: Taofeek K. Owonikoko 404-778-5575 email@example.com|
|Principal Investigator: Taofeek K. Owonikoko|
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center||Recruiting|
|Chicago, Illinois, United States, 60637-1470|
|Contact: Ravi Salgia 773-702-1000 firstname.lastname@example.org|
|Principal Investigator: Ravi Salgia|
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital||Recruiting|
|Baltimore, Maryland, United States, 21231|
|Contact: Christine L. Hann 410-502-0678 email@example.com|
|Principal Investigator: Christine L. Hann|
|United States, Montana|
|Billings, Montana, United States, 59107-7000|
|Contact: Jorge J. Nieva 406-435-7415 firstname.lastname@example.org|
|Principal Investigator: Jorge J. Nieva|
|United States, North Carolina|
|University of North Carolina||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Thomas E. Stinchcombe 919-966-9268 email@example.com|
|Principal Investigator: Thomas E. Stinchcombe|
|United States, Ohio|
|Case Western Reserve University||Recruiting|
|Cleveland, Ohio, United States, 44106|
|Contact: Afshin Dowlati 216-844-8573 firstname.lastname@example.org|
|Principal Investigator: Afshin Dowlati|
|Ohio State University Medical Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Gregory A. Otterson 614-293-9424 email@example.com|
|Principal Investigator: Gregory A. Otterson|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37232|
|Contact: Leora Horn 615-936-3524 firstname.lastname@example.org|
|Principal Investigator: Leora Horn|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics||Recruiting|
|Madison, Wisconsin, United States, 53792|
|Contact: Afshin Dowlati 216-844-8573 email@example.com|
|Principal Investigator: Afshin Dowlati|
|Principal Investigator:||Alberto Chiappori||H. Lee Moffitt Cancer Center and Research Institute|