Clinical trial NCT01441349: Irinotecan/Cisplatin With or Without Simvastatin in Chemo-naive Patients With Extensive Disease-small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Small Cell Lung Carcinoma
Keywords: Simvastatin
SCLC
Extensive Disease
Lead sponsor: National Cancer Center, Korea
Sponsor class: OTHER_GOV
First posted: 2011-09-27
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 1-year survival rate
timeFrame: every 8 weeks
Secondary outcomes:
measure: Tumor Response rate
timeFrame: every 2 cycles or 6 weeks
measure: Progression free survival
timeFrame: every 2 cycles or 6 weeks.
measure: Toxicity profile
timeFrame: every 3 weeks
Other outcomes:
Locations:
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center , Korea
state: Gyeonggi-do
Study officials:
affiliation: National Cancer Center
name: JI-YOUN HAN, M.D. PhD.
role: PRINCIPAL_INVESTIGATOR
References: