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Irinotecan/Cisplatin Plus Simvastatin in ED-SCLC

This study is currently recruiting participants.
Verified by National Cancer Center, Korea, December 2007

Sponsored by: National Cancer Center, Korea
Information provided by: National Cancer Center, Korea
ClinicalTrials.gov Identifier: NCT00452634
  Purpose

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, we will conduct this phase II trial to evaluate the efficacy & toxicity of irinotecan/cisplatin plus simvastatin in patients with chemo-naïve ED-SCLC.


Condition Intervention Phase
Small Cell Lung Cancer
Drug: Irinotecan
Drug: Cisplatin
Drug: Simvastatin
Phase II

MedlinePlus related topics:   Cancer    Lung Cancer   

ChemIDplus related topics:   Cisplatin    Irinotecan    Irinotecan hydrochloride    Disulfiram    Simvastatin   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:   A Phase II Study of Irinotecan/Cisplatin Plus Simvastatin in Chemo-Naive Patients With Extensive Disease-Small Cell Lung Cancer

Further study details as provided by National Cancer Center, Korea:

Primary Outcome Measures:
  • 1-year survival & overall survival [ Time Frame: the first day of treatment to death or last survival confirm date ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor response rate [ Time Frame: the ratio between the number of responders and number of patients assessable for tumor resonse ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: the first day of treatment to the date that disease progression is reported ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: the first date of treatment to 30 days after the last dose of study drug ] [ Designated as safety issue: Yes ]

Estimated Enrollment:   61
Study Start Date:   April 2006
Estimated Study Completion Date:   February 2008
Estimated Primary Completion Date:   February 2008 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
1: Experimental 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

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.

  Eligibility
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

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.
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00452634

Contacts
Contact: Ji-Youn Han, M.D.,Ph.D.     +82-31-920-1154     jymama@ncc.re.kr    

Locations
Korea, Republic of, Gyenggi
National Cancer Center, Korea     Recruiting
      Goyang-si, Gyenggi, Korea, Republic of, 411-769
      Contact: Ji-Youn Han, M.D.,Ph.D.     +82-31-920-1154        
      Principal Investigator: Ji-Youn Han, M.D.            
      Sub-Investigator: Jin Soo Lee, M.D.            
      Sub-Investigator: Heung Tae Kim, M.D.            
      Sub-Investigator: Kun Young Lim, M.D.            
      Sub-Investigator: Tak Yun, M.D.            

Sponsors and Collaborators
National Cancer Center, Korea

Investigators
Principal Investigator:     Ji-Youn Han, M.D.,Ph.D.     National Cancer Center, Korea    
  More Information


Responsible Party:   National Cancer Center, Korea ( Ji-Youn Han )
Study ID Numbers:   NCCCTS-06-176
First Received:   March 26, 2007
Last Updated:   January 25, 2008
ClinicalTrials.gov Identifier:   NCT00452634
Health Authority:   South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by National Cancer Center, Korea:
Irinotecan  
cisplatin  
Simvastatin  
Extensive disease  
SCLC  

Study placed in the following topic categories:
Disulfiram
Thoracic Neoplasms
Carcinoma, Neuroendocrine
Simvastatin
Irinotecan
Carcinoma
Neuroendocrine Tumors
Carcinoma, Small Cell
Neuroectodermal Tumors
Cisplatin
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Adenocarcinoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Antimetabolites
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antilipemic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Enzyme Inhibitors
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Radiation-Sensitizing Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on October 20, 2008




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