Irinotecan/Cisplatin With or Without Simvastatin in Chemo-naive Patients With Extensive Disease-small Cell Lung Cancer
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|ClinicalTrials.gov Identifier: NCT01441349|
Recruitment Status : Recruiting
First Posted : September 27, 2011
Last Update Posted : August 25, 2017
|Condition or disease||Intervention/treatment||Phase|
|Small Cell Lung Carcinoma||Drug: IP chemotherapy Drug: IP chemotherapy plus simvastatin||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||192 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||August 2011|
|Estimated Primary Completion Date :||December 2019|
|Estimated Study Completion Date :||December 2020|
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
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01441349
|Contact: Sung JIn Yoon, RNemail@example.com|
|Contact: JONGHEE HAN, RNfirstname.lastname@example.org|
|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 email@example.com|
|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|