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A Randomized Phase II Study of Irinotecan/Cisplatin With or Without Simvastatin in Chemo-naive Patients With Extensive Disease-small Cell Lung Cancer

Phase 2
18 Years
Open (Enrolling)
Small Cell Lung Carcinoma

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Trial Information

A Randomized Phase II Study of Irinotecan/Cisplatin With or Without Simvastatin in Chemo-naive Patients With Extensive Disease-small Cell Lung Cancer

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

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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

1-year survival rate

Outcome Description:

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.

Outcome Time Frame:

every 8 weeks

Safety Issue:


Principal Investigator


Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Center


South Korea: Korea Food and Drug Administration (KFDA)

Study ID:




Start Date:

August 2011

Completion Date:

January 2015

Related Keywords:

  • Small Cell Lung Carcinoma
  • Simvastatin
  • SCLC
  • Extensive Disease
  • Carcinoma
  • Lung Neoplasms
  • Small Cell Lung Carcinoma