Small Cell Lung Carcinoma
Conditions
Keywords
Simvastatin, SCLC, Extensive Disease
Brief summary
The purpose of this study is to compare the efficacy of Simvastatin and Irinotecan/Cisplatin chemotherapy with Irinotecan/Cisplatin chemotherapy alone in Extensive disease-small cell lung cancer.
Detailed description
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.
Interventions
DRUGIP chemotherapy
Irinotecan/cisplatin (IP) chemotherapy * Cisplatin(30 mg/m2) diluted into 150 ml of 0.9% NS for IV over 30 min on day 1 &8. * Irinotecan(65mg/m2) diluted into 200ml of 5DW IV over 90 min on day 1 & 8 * Every 21 days
DRUGIP chemotherapy plus simvastatin
* Cisplatin(30mg/m2)diluted into 150 ml of 0.9% NS for IV over 30 min on day 1 &8 * Irinotecan( 65 mg/m2) diluted into 200ml of 5DW IV over 90 min on day 1& 8. * Every 21days. * Simvastatin 40 mg per day orally D1of cycle 1
Sponsors
National Cancer Center, Korea
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed SCLC * Extensive - stage disease, defined as disease extending beyond one hemithorax or involving contralateral mediastinal, hilar or supraclavicular lymph nodes, and/ or pleural effusion * ever smoker( have smoked\> 100 cigarettes in entire lifetime * No prior chemotherapy, immunotherapy, or radiotherapy * Measurable disease according to RECIST 1.1 * Patient compliance that allow adequate follow - up * Adequate hematologic , hepatic and renal function. * Written informed consent that is consistent with International Conference on Harmonization (ICH) - Good Clinical Practice (GCP) guidelines * Males of females at least 18 years of age * If female : childbearing potential either terminated by surgery, radiation, or menopause or attenuated by use of an approved contraceptive method(intrauterine device, birth control pills, or barrier device)during for 3 months after trial. If male, use of an approved contraceptive method during the study and 3 months afterwards. Females with childbearing potential must have a urine negative hCG test within 7 days prior to the study enrollment. * No concomitant prescriptions including cyclosporin A, valproic acid, phenobarbital, phenytoin, ketoconazole. * Patients with brain metastasis are allowed unless there were clinically significant neurological symptoms or signs.
Exclusion criteria
* Inability to comply with protocol or study procedures. * A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study. * A serious cardiac condition, such as myocardial infarction with 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV. * Second primary malignancy that is clinically detectable at the time of consideration for study enrollment. * Concurrent administration of any other antitumor therapy. * Pregnant or Breast-feeding. * Taking simvastatin or Any contraindications for therapy with simvastatin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-year survival rate | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response rate | 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 | 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 profile | 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. |
Countries
South Korea
Outcome results
None listed