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Anticancer Activity of Nicotinamide on Lung Cancer

Information source: Chungbuk National University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Non-Small-Cell Lung Carcinoma

Intervention: Nicotinamide (Drug)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: Il Yeong Park, Ph.D.

Official(s) and/or principal investigator(s):
Il Yeong Park, PhD, Study Director, Affiliation: Chungbuk National University

Overall contact:
Young-Chul Kim, MD, PhD, Phone: +82-61-379-7614, Email: kyc0923@jnu.ac.kr


Nicotinamide is an inhibitor of human sirtuins (HDAC III), and is found to re-activate epigenetically silenced tumor suppressors, RUNX3 (runt-related gene 3) and others, in cancer cells. Nicotinamide was found to be effective in several animal cancer models including lung, bladder, liver, etc. The purpose of this study is to determine whether nicotinamide is also effective in the treatment of human lung cancer.

Clinical Details

Official title: Randomized Double-blinded Comparative Trial to Study the Add-on Activity of Combination Treatment of Nicotinamide on Progression Free Survival for EGFR Mutated Lung Cancer Terminal Stage Patients Being Treated With Gefitinib or Erlotinib

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome: Hazard ratio (PFS) of the nicotinamide arm to the placebo arm

Secondary outcome:

Response rate

Quality of life

Overall survival

Detailed description: The standard therapy to the EGFR (epidermal growth factor receptor) mutation positive non-small-cell lung cancer patients who are not eligible to operation is to administer EGFR-TKIs (tyrosine kinase inhibitors, gefitinib or erlotinib). To determine the effectiveness of nicotinamide on lung cancer, nicotinamide or placebo tablet will be co-administered with gefitinib or erlotinib for two years until the event or censoring occurs. The stratified block randomization was designed with 3 covariates (EGFR mutation status, kind of EGFR-TKI, ECOG (Eastern Cooperative Oncology Group) performance status score variation). The size of lesions will be checked every other months by radiology. PD (progressive disease) will be assessed according to RECIST(Response Evaluation Criteria in Solid Tumors)1. 1. After observing 36 events, an interim analysis of hazard ratio by Cox proportional hazard regression will be performed. The final analysis will be done by the same protocol after observation of 72 events. The significance level of the interim and final analysis were set to 0. 0075 and 0. 0209 respectively. Response rate, quality of life (measured by 10 questions at every visit), and overall survival will be analysed together. All other adverse reactions will be analysed and reported, if there.


Minimum age: 19 Years. Maximum age: 80 Years. Gender(s): Both.


Inclusion Criteria:

- Operation-impossible stage 4 non-small-cell lung carcinoma (NSCLC), or recurred

terminal stage NSCLC after previous operation or radiation therapy

- EGFR mutated (exon 19 deletion or L858R mutation)

- Life expectation more than 3 months

- More than 1 measurable lesions by RECIST 1. 1 which were not exposed to radiation


- ECOG (Eastern Cooperative Oncology Group ) performance status grade 0~2

- Who signed the informed consent form

Exclusion Criteria:

- Who had received chemotherapy or EGFR tyrosin kinase inhibitors previously, except

whom had received operation at least 6 months ago and received supplementary chemotherapy

- Who has metastasized brain lesion that needs operation or radiation therapy

- Above grade 2, CTCAE (Common Toxicity Criteria for Adverse Effects) 4. 0 criteria for

blood, liver and kidney

- Who does Not agree to contraception

- Who has allergy to nicotinamide

Locations and Contacts

Young-Chul Kim, MD, PhD, Phone: +82-61-379-7614, Email: kyc0923@jnu.ac.kr

Chonnam National University Hwasun Hospital, Hwasun, Chonnam 519-763, Korea, Republic of; Recruiting
Young-Chul Kim, MD, PhD, Phone: +82-61-379-7614, Email: kyc0923@jnu.ac.kr
Sun Hyung Park, Nurse, Phone: +82-61-379-7851, Email: nr-shpark@hanmail.net
Additional Information

Related publications:

Li QL, Kim HR, Kim WJ, Choi JK, Lee YH, Kim HM, Li LS, Kim H, Chang J, Ito Y, Youl Lee K, Bae SC. Transcriptional silencing of the RUNX3 gene by CpG hypermethylation is associated with lung cancer. Biochem Biophys Res Commun. 2004 Jan 30;314(1):223-8.

Li QL, Ito K, Sakakura C, Fukamachi H, Inoue Ki, Chi XZ, Lee KY, Nomura S, Lee CW, Han SB, Kim HM, Kim WJ, Yamamoto H, Yamashita N, Yano T, Ikeda T, Itohara S, Inazawa J, Abe T, Hagiwara A, Yamagishi H, Ooe A, Kaneda A, Sugimura T, Ushijima T, Bae SC, Ito Y. Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell. 2002 Apr 5;109(1):113-24.

Avalos JL, Bever KM, Wolberger C. Mechanism of sirtuin inhibition by nicotinamide: altering the NAD(+) cosubstrate specificity of a Sir2 enzyme. Mol Cell. 2005 Mar 18;17(6):855-68.

Black JC, Mosley A, Kitada T, Washburn M, Carey M. The SIRT2 deacetylase regulates autoacetylation of p300. Mol Cell. 2008 Nov 7;32(3):449-55. doi: 10.1016/j.molcel.2008.09.018.

Lee YS, Lee JW, Jang JW, Chi XZ, Kim JH, Li YH, Kim MK, Kim DM, Choi BS, Kim EG, Chung JH, Lee OJ, Lee YM, Suh JW, Chuang LS, Ito Y, Bae SC. Runx3 inactivation is a crucial early event in the development of lung adenocarcinoma. Cancer Cell. 2013 Nov 11;24(5):603-16. doi: 10.1016/j.ccr.2013.10.003.

Omar MF, Ito K, Nga ME, Soo R, Peh BK, Ismail TM, Thakkar B, Soong R, Ito Y, Salto-Tellez M. RUNX3 downregulation in human lung adenocarcinoma is independent of p53, EGFR or KRAS status. Pathol Oncol Res. 2012 Oct;18(4):783-92. Epub 2012 Jun 24.

Kim WJ, Lee JW, Quan C, Youn HJ, Kim HM, Bae SC. Nicotinamide inhibits growth of carcinogen induced mouse bladder tumor and human bladder tumor xenograft through up-regulation of RUNX3 and p300. J Urol. 2011 Jun;185(6):2366-75. doi: 10.1016/j.juro.2011.02.017. Epub 2011 Apr 21. Erratum in: J Urol. 2011 Aug;186(2):762.

Park SY, Lee KB, Lee MJ, Bae SC, Jang JJ. Nicotinamide inhibits the early stage of carcinogen-induced hepatocarcinogenesis in mice and suppresses human hepatocellular carcinoma cell growth. J Cell Physiol. 2012 Mar;227(3):899-908. doi: 10.1002/jcp.22799.

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Peck B, Chen CY, Ho KK, Di Fruscia P, Myatt SS, Coombes RC, Fuchter MJ, Hsiao CD, Lam EW. SIRT inhibitors induce cell death and p53 acetylation through targeting both SIRT1 and SIRT2. Mol Cancer Ther. 2010 Apr;9(4):844-55. doi: 10.1158/1535-7163.MCT-09-0971. Epub 2010 Apr 6.

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Knip M, Douek IF, Moore WP, Gillmor HA, McLean AE, Bingley PJ, Gale EA; European Nicotinamide Diabetes Intervention Trial Group. Safety of high-dose nicotinamide: a review. Diabetologia. 2000 Nov;43(11):1337-45. Review.

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Starting date: March 2015
Last updated: April 29, 2015

Page last updated: August 23, 2015

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