Clinical trial NCT01533181
Conditions: Recurrent Small Cell Lung Carcinoma
Sponsor: National Cancer Institute (NCI)
Start date: 2012-02-01; Completion date: 2014-11-01
Enrollment: 44 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: OS-906 daily, continuously, every 3 weeks. arm 2: 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.
Interventions: intervention 1: Laboratory Biomarker Analysis intervention 2: Linsitinib intervention 3: Pharmacological Study intervention 4: Topotecan Hydrochloride
Intervention descriptions: intervention 1: Correlative studies intervention 2: 150 mg given orally (PO) twice a day (BID) intervention 3: Correlative studies intervention 4: 1.5 mg/m\^2 intravenously (IV) or 2.3 mg/m\^2 orally (PO)

Protocol documents: