Irinotecan/Cisplatin With or Without Simvastatin in Chemo-naive Patients With Extensive Disease-small Cell Lung Cancer
Recruitment status was: Recruiting
|Small Cell Lung Carcinoma||Drug: IP chemotherapy Drug: IP chemotherapy plus simvastatin||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized Phase II Study of Irinotecan/Cisplatin With or Without Simvastatin in Chemo-naive Patients With Extensive Disease-small Cell Lung Cancer|
- 1-year survival rate [ Time Frame: every 8 weeks ]Survival time will be calculated from the date of study treatment start to the date of death.( or date last seen ) Follow - up visits are conducted every 8 weeks to obtain meaningful data on time- to event variables. Assessment will continue until death or 12 months after treatment.
- Tumor Response rate [ Time Frame: every 2 cycles or 6 weeks ]The response rate will be determined by the number of patients with complete and partial responses according to RECIST criteria 1.1
- Progression free survival [ Time Frame: every 2 cycles or 6 weeks. ]Progression free survival will be calculated from the date of study treatment start to the first objective documentation of progressive disease or to the date of death, whichever occurs first.
- Toxicity [ Time Frame: every 3 weeks ]Safety will be evaluated by the frequency, severity, and relationship of adverse event graded by NCI Common Toxicity Criteria version 4.0 that occur during the treatment and follow up periods.
|Study Start Date:||August 2011|
|Estimated Study Completion Date:||January 2015|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Active Comparator: Control arm
IP chemotherapy arm
Drug: IP chemotherapy
Irinotecan/cisplatin (IP) chemotherapy
Other Name: IP
Experimental: Treatment arm
IP chemotherapy plus simvastatin arm
Drug: IP chemotherapy plus simvastatin
Other Name: IPSimva
Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been used to treat hypercholesterolemia. Besides the lipid lowering effects, they also act as anti-inflammatory and anti-cancer agents. Recently the investigators demonstrated a synergistic cytotoxicity between Simvastatin and Irinotecan in human lung cancer cells. Simvastatin enhances Irinotecan-induced apoptosis by inhibition of proteasome activity. All of these additional actions may counteract harmful effects of smoking-induced chronic inflammation. These properties together with a high safety profile have made Statins more attractive drug for small cell lung cancer (SCLC), the highly smoking-related cancer.
Given the promising preclinical anti-tumor and anti-inflammatory effects of Simvastatin in SCLC, recently the investigators conducted a phase II study of Simvastatin and Irinotecan/Cisplatin (IP) chemotherapy in chemo-naïve- patients with Extensive disease-small cell lung cancer (ED-SCLC). The 1-year survival rate was 39.3%. The median overall survival (OS) and progression free survival (PFS) was 11.0 months and 6.1 months, respectively. Overall relative risk (RR) was 75%. The most common toxicity was neutropenia (67%). The efficacy was significantly associated with smoking-status. Compared with never-smokers, ever-smokers had higher RR (40% v 78%, P=0.01) and longer PFS (2.5 months v 6.4 months, P=0.018) and showed a trend toward improved OS (9.0 months v 11.2 months, P=0.095). The effect of smoking on survival was apparent when subdividing ever smokers according to pack-years (PY). Ever-smokers who smoked > 65 PY showed significantly longer OS compared to ever-smokers who smoked <= 65 PY or never-smokers (20.6 months v 10.6 months v 9.0 months, log-rank P=0.032). In multivariate analysis, PY > 65 was predictive for longer survival (hazard ratio) HR=0.377 [95% CI (confidence interval), 0.157-0.905]). These findings suggest that the addition of Simvastatin to Irinotecan and Cisplatin improved efficacy in ever-smokers with ED-SCLC. The survival benefit of this combination seems apparent in heavy-smokers.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01441349
|Contact: Sung JIn Yoon, RNfirstname.lastname@example.org|
|Contact: JONGHEE HAN, RNemail@example.com|
|Korea, Republic of|
|National Cancer Center , Korea||Recruiting|
|Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769|
|Contact: JONGHEE HAN, RN 82-31-920-0409 firstname.lastname@example.org|
|Sub-Investigator: Jin Soo Lee, MD|
|Sub-Investigator: Heung Tae Kim, MD|
|Sub-Investigator: Tak Yun, MD|
|Sub-Investigator: Young Joo Lee, MD|
|Sub-Investigator: Geon Kook Lee, MD|
|Sub-Investigator: Soo Hyun Lee, MD|
|Principal Investigator:||JI-YOUN HAN, M.D. PhD.||National Cancer Center|