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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2011 by National Cancer Center, Korea
Sponsor:
Information provided by (Responsible Party):
Ji-youn Han, National Cancer Center, Korea
ClinicalTrials.gov Identifier:
NCT01441349
First received: September 14, 2011
Last updated: October 18, 2012
Last verified: November 2011
  Purpose

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 Intervention Phase
Small Cell Lung Carcinoma
Drug: IP chemotherapy
Drug: IP chemotherapy plus simvastatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 1-year survival rate [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]
    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:
  • Tumor Response rate [ Time Frame: every 2 cycles or 6 weeks ] [ Designated as safety issue: No ]
    The response rate will be determined by the number of patients with complete and partial responses according to RECIST criteria 1.1

  • Progression free survival [ Time Frame: every 2 cycles or 6 weeks. ] [ Designated as safety issue: No ]
    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.

  • Toxicity [ Time Frame: every 3 weeks ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 192
Study Start Date: August 2011
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01441349

Contacts
Contact: Sung JIn Yoon, RN 82-31-920-0405 jinijyniya@ncc.re.kr
Contact: JONGHEE HAN, RN 82-31-920-0409 hanjonghee@ncc.re.kr

Locations
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    hanjonghee@ncc.re.kr   
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
Investigators
Principal Investigator: JI-YOUN HAN, M.D. PhD. National Cancer Center
  More Information

No publications provided

Responsible Party: Ji-youn Han, Head, lung cancer center, National Cancer Center, Korea
ClinicalTrials.gov Identifier: NCT01441349     History of Changes
Other Study ID Numbers: NCCCTS-11-527
Study First Received: September 14, 2011
Last Updated: October 18, 2012
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by National Cancer Center, Korea:
Simvastatin
SCLC
Extensive Disease

Additional relevant MeSH terms:
Small Cell Lung Carcinoma
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Irinotecan
Cisplatin
Simvastatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014