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

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

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer Statins

Drug Information available for: Cisplatin Simvastatin Irinotecan U 101440E Irinotecan hydrochloride

U.S. FDA Resources

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 response ] [ 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:	January 2010
Estimated Primary Completion Date:	November 2009 (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

No publications provided

Responsible Party:	National Cancer Center, Korea ( Ji-Youn Han )
Study ID Numbers:	NCCCTS-06-176
Study First Received:	March 26, 2007
Last Updated:	December 24, 2008
ClinicalTrials.gov Identifier:	NCT00452634 History of Changes
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:

Antimetabolites
Disulfiram
Thoracic Neoplasms
Carcinoma, Neuroendocrine
Simvastatin
Antilipemic Agents
Irinotecan
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Carcinoma
Neuroendocrine Tumors
Carcinoma, Small Cell

Neuroectodermal Tumors
Radiation-Sensitizing Agents
Cisplatin
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Adenocarcinoma
Antineoplastic Agents, Phytogenic
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Antimetabolites
Thoracic Neoplasms
Molecular Mechanisms of Pharmacological Action
Carcinoma, Neuroendocrine
Antineoplastic Agents
Neoplasms, Nerve Tissue
Irinotecan
Physiological Effects of Drugs
Neoplasms by Site
Respiratory Tract Diseases
Cisplatin
Lung Neoplasms
Neoplasms, Germ Cell and Embryonal
Therapeutic Uses
Respiratory Tract Neoplasms

Neoplasms by Histologic Type
Simvastatin
Antilipemic Agents
Enzyme Inhibitors
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions
Neuroendocrine Tumors
Carcinoma
Carcinoma, Small Cell
Neuroectodermal Tumors
Neoplasms
Radiation-Sensitizing Agents
Lung Diseases
Adenocarcinoma

ClinicalTrials.gov processed this record on September 10, 2009