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Irinotecan/Cisplatin Plus Simvastatin in Extensive Disease-Small Cell Lung Cancer (ED-SCLC)

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. Read our disclaimer for details. Identifier: NCT00452634
Recruitment Status : Completed
First Posted : March 27, 2007
Last Update Posted : June 19, 2013
Information provided by (Responsible Party):
Ji-youn Han, National Cancer Center, Korea

Brief Summary:
3-Hydroxy-3-methylglutaryl CoA reductase inhibitors, commonly referred to as the statins, have proven therapeutic and preventative effects in cardiovascular diseases. Recently, there are emerging interests in their use as anticancer agents based on preclinical evidence of their antiproliferative, proapoptotic, anti-invasive, and radiosensitizing properties. Inhibition of 3-hydroxy-3-methylglutaryl CoA reductase by the statins interferes with the rate-limiting step of the mevalonate pathway, leading to reduced levels of mevalonate and its downstream products, many of which play important roles in critical cellular functions such as membrane integrity, cell signaling, protein synthesis, and cell cycle progression. Perturbations of these processes in neoplastic cells by the statins may therefore result in control of tumor initiation, growth, and metastasis. The statins have demonstrated growth inhibitory activity in cancer cell lines and preclinical tumor models in animals. Simvastatin, a member of the statin family, profoundly impaired basal and growth factor-stimulated SCLC cell growth in vitro and induced apoptosis. SCLC cells treated with simvastatin were sensitized to the effects of the chemotherapeutic agent etoposide. Moreover, SCLC tumour growth in vivo was inhibited by simvastatin. Therefore, the investigators will conduct this phase II trial to evaluate the efficacy & toxicity of irinotecan/cisplatin plus simvastatin in patients with chemo-naïve ED-SCLC.

Condition or disease Intervention/treatment Phase
Small Cell Lung Cancer Drug: Irinotecan Drug: Cisplatin Drug: Simvastatin Phase 2

Detailed Description:

Cisplatin-30 mg/m2 on day 1 and 8 repeat q 3 weeks Irinotecan-65 mg/m2 on day1 and 8 repeat q 3 weeks Simvastatin 40 mg per day orally from D1 of cycle 1

Treatment will be continued until disease progression, unacceptable toxicity, or patients' refusal.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Irinotecan/Cisplatin Plus Simvastatin in Chemo-naive Patients With Extensive Disease-Small Cell Lung Cancer
Study Start Date : April 2006
Actual Primary Completion Date : November 2009
Actual Study Completion Date : May 2010

Arm Intervention/treatment
Experimental: study arm Drug: Irinotecan
Irinotecan 65mg/m2/iv over 90min on day 1 and 8, repeat Q 3weeks. until disease progression, unacceptable toxicity or patients' refusal.

Drug: Cisplatin
Cisplatin 30mg/m2/iv over 30min on day 1 and 8, repeat Q 3weeks. until disease progression, unacceptable toxicity or patients' refusal.

Drug: Simvastatin
simvastatin 40mg/QD, PO, daily, every 3 weeks

Primary Outcome Measures :
  1. 1-year survival & overall survival [ Time Frame: the first day of treatment to death or last survival confirm date ]

Secondary Outcome Measures :
  1. Tumor response rate [ Time Frame: the ratio between the number of responders and number of patients assessable for tumor response ]
  2. Time to progression [ Time Frame: the first day of treatment to the date that disease progression is reported ]
  3. Toxicity [ Time Frame: the first date of treatment to 30 days after the last dose of study drug ]

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:

  • Histologic or cytologic diagnosis of SCLC
  • Extensive-stage disease, defined as disease extending beyond one hemithorax or involving contralateral mediastinal, hilar or supraclavicular lymph nodes, and/or pleural effusion.
  • No prior chemotherapy, immunotherapy, or radiotherapy
  • Performance status of 0, 1, 2 on the ECOG criteria.
  • At least one unidimensional measurable lesion meeting Response Evaluation Criteria in Solid Tumors (RECIST. 2000).
  • Patient compliance that allow adequate follow-up.
  • Adequate hematologic (WBC count ≥ 4,000/mm3, platelet count ≥ 150,000/mm3), hepatic (bilirubin level ≤ 1.5 mg/dL, AST/ALT ≤ 80 IU/L), and renal (creatinine concentration ≤ 1.5 mg/dL) function.
  • Informed consent from patient or patient's relative.
  • Males or 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 [IUD], birth control pills, or barrier device) during and 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 within 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.

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): NCT00452634

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Korea, Republic of
National Cancer Center, Korea
Goyang-si, Gyenggi, Korea, Republic of, 411-769
Sponsors and Collaborators
National Cancer Center, Korea
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Principal Investigator: Ji-Youn Han, M.D.,Ph.D. National Cancer Center, Korea
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Responsible Party: Ji-youn Han, Head of Lung Cancer Center, National Cancer Center, Korea Identifier: NCT00452634    
Other Study ID Numbers: NCCCTS-06-176
First Posted: March 27, 2007    Key Record Dates
Last Update Posted: June 19, 2013
Last Verified: June 2013
Keywords provided by Ji-youn Han, National Cancer Center, Korea:
Extensive disease
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticholesteremic Agents
Hypolipidemic Agents
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors