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Irinotecan/Cisplatin With or Without Simvastatin in Chemo-naive Patients With Extensive Disease-small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01441349
Recruitment Status : Recruiting
First Posted : September 27, 2011
Last Update Posted : September 10, 2020
Information provided by (Responsible Party):
Ji-youn Han, National Cancer Center, Korea

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.

Condition or disease Intervention/treatment Phase
Small Cell Lung Carcinoma Drug: IP chemotherapy Drug: IP chemotherapy plus simvastatin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 192 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : August 2011
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Control arm
IP chemotherapy arm
Drug: IP 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
Other Name: IP

Experimental: Treatment arm
IP chemotherapy plus simvastatin arm
Drug: IP 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
Other Name: IPSimva

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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

  2. 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.

  3. Toxicity profile [ 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

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 identifier (NCT number): NCT01441349

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Contact: Sung JIn Yoon, RN 82-31-920-0405
Contact: JONGHEE HAN, RN 82-31-920-0409

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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   
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         
Sponsors and Collaborators
National Cancer Center, Korea
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Principal Investigator: JI-YOUN HAN, M.D. PhD. National Cancer Center
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Responsible Party: Ji-youn Han, Head, lung cancer center, National Cancer Center, Korea Identifier: NCT01441349    
Other Study ID Numbers: NCCCTS-11-527
First Posted: September 27, 2011    Key Record Dates
Last Update Posted: September 10, 2020
Last Verified: September 2020
Keywords provided by Ji-youn Han, National Cancer Center, Korea:
Extensive Disease
Additional relevant MeSH terms:
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Small Cell Lung Carcinoma
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors