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

NCT ID: NCT00452634

Last Updated: 2013-06-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-04-30
• Study Completion Date: 2010-05-31

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.

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.

Conditions

Small Cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

study arm

Group Type: EXPERIMENTAL

Irinotecan

Intervention Type: DRUG

Irinotecan 65mg/m2/iv over 90min on day 1 and 8, repeat Q 3weeks. until disease progression, unacceptable toxicity or patients' refusal.

Cisplatin

Intervention Type: DRUG

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

Simvastatin

Intervention Type: DRUG

simvastatin 40mg/QD, PO, daily, every 3 weeks

Interventions

Irinotecan

Irinotecan 65mg/m2/iv over 90min on day 1 and 8, repeat Q 3weeks. until disease progression, unacceptable toxicity or patients' refusal.

Intervention Type: DRUG

Cisplatin

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

Intervention Type: DRUG

Simvastatin

simvastatin 40mg/QD, PO, daily, every 3 weeks

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Center, Korea

OTHER_GOV

Sponsor Role: lead

Responsible Party

Ji-youn Han

Head of Lung Cancer Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ji-Youn Han, M.D.,Ph.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Center, Korea

Locations

National Cancer Center, Korea

Goyang-si, Gyenggi, South Korea

Countries

South Korea

Other Identifiers

NCCCTS-06-176

Identifier Type: -

Identifier Source: org_study_id