Sunitinib as a Second-line Treatment for Patients With Recurrent Small Cell Lung Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Sunitinib as a Second-line Treatment for Patients With Recurrent Small Cell Lung Cancer.|
- Tumor response rate [ Time Frame: at 4week and every 8 weeks ] [ Designated as safety issue: No ]The response rate will be determined by the number of patients with complete and partial responses according to RECIST criteria.
- Overall survival [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]Survival time will be calculated from the date of study treatment start to the date of death (or date last seen).
- Progression-Free Survival [ Time Frame: at 4 week and every 8 weeks ] [ Designated as safety issue: No ]Progression free survival will be calculated from the date of study treatment start to the first objective documentation of progressive disease or death.
- Toxicity [ Time Frame: every 4 weeks ] [ Designated as safety issue: No ]Safety will be evaluated by the frequency, severity, and relationship of adverse events graded by NCI Common Toxicity Criteria (CTC) version 3.0 that occur during the treatment and follow-up periods.
|Study Start Date:||March 2008|
|Study Completion Date:||September 2012|
|Primary Completion Date:||February 2012 (Final data collection date for primary outcome measure)|
Experimental: Single arm
Single arm (sunitinib arm) until PD, unacceptable toxicity, patients refused
sunitinib (50mg/day, 4weeks on, 2 weeks off) Repeat every 6 weeks. Treatment will continue until disease progression, unacceptable toxicity, or patients' refusal.
Chemotherapy is the primary treatment option for patients with small cell lung cancer, leading to a 5-year survival of about 20% in limited disease (LD), and less than 5% in extensive disease (ED). Although initial tumor response rate to chemotherapy is very high (up to 96% for LD and up to 65% in ED), SCLC relapses in approximately 4 months in ED and 12 months in LD adn despite the administration of second-line chemotherapy, the overall median survival of patients with limited and extensive disease is approximately 18 and 9 months, respectively. In the setting of second-line therapy, response rates to chemotherapy range between 15 and 25%, with median survival in the range of 4-6 months. Second-line therapeutic options include cyclophosphamide, doxorubicin and vincristine (CAV) given every 3 weeks or topotecan, which have similar response rates, time to progression and survival in the two treatment arms (topotecan 24%, 13 and 24.7 weeks; CAV 18%, 12 and 22 weeks, respectively). However, both treatments however have substantial toxicities, with 9% of patients on trial withdrawing for toxicity reasons. Treatment-associated mortality was as high as 4.7% (possibly and definitely related), and many patients required transfusion support. Thus, while these treatments have acceptable activity second-line, more active and less toxic treatments are required for this patient population.Tyrosine kinase inhibitors have become a promising new class of anti-cancer agents owing to the importance of their targets in tumor proliferation, survival (apoptosis), angiogenesis, motility, and metastasis Among the most important receptor tyrosine kinases that regulate tumor angiogenesis are the vascular endothelial growth factor receptor 2 (VEGFR2/Flk-1/KDR), PDGFR, and the fibroblast growth factor (FGF) receptor family. These receptors belong to the split-kinase domain superfamily, which also includes Kit, the receptor for stem cell factor (SCF). Kit is frequently expressed in multiple hematologic and non-hematologic malignancies. It can also be activated in an autocrine fashion by coexpression with SCF, as is the case in SCLC, where approximately 70% of tumors and cell lines coexpress Kit and SCF at some level. Inhibition of Kit using small molecule inhibitors results in growth inhibition of multiple SCLC cell lines. Sunitinib, a novel small molecule receptor tyrosine kinase inhibitor with direct antitumor as well as antiangiogenic activity via targeting the vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), KIT, and FLT3 receptor tyrosine kinases, which showed anti-tumor activity in mouse xenograft model of SCLC. Therefore, the investigators will conduct a phase II trial to evaluate the efficacy and toxicity of Sunitinib in patients with recurrent SCLC.-Single arm
-Sunitinib(50mg/day, 4weeks on, 2 weeks off) Repeat every 6 weeksTreatment will continue until disease progression, unacceptable toxicity, or patients' refusal
Please refer to this study by its ClinicalTrials.gov identifier: NCT00620347
|Korea, Republic of|
|National Cancer Center, Korea|
|Goyang-si, Gyeonggi-do, Korea, Republic of, 411-764|
|Principal Investigator:||Ji-Youn Han, M.D.,Ph.D.||National Cancer Center, Korea|