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Non-Small-Cell Lung CarcinomaPhase 2/3NCT02416739

Anticancer Activity of Nicotinamide on Lung Cancer

A Phase 2/3 study testing Nicotinamide in people with Non-Small-Cell Lung Carcinoma, run by Il Yeong Park, Ph.D. at 1 site in South Korea.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small-Cell Lung Carcinoma
What is being tested?
Nicotinamide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
110 participants
Where
1 siteSouth Korea
Study dates
Mar 2015to Jun 2020
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 previously
  • ECOG (Eastern Cooperative Oncology Group ) performance status grade 0~2
  • Who signed the informed consent form

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Chonnam National University Hwasun Hospital

    Hwasun, Chonnam, 58128

Other trials in South Korea

About this study

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

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.

Read the 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.

Being tested
Nicotinamide
Keywords
EGFR mutated lung cancer
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NicotinamideDrug

    Also called Amina-X

    Nicotinamide (1g/day) or placebo treatment is added to the standard drug treatment (gefitinib or erlotinib) to EGFR mutated NSCLC patients

Study groups in NCT02416739
Study groupRoleWhat they receive
NicotinamideExperimentalNicotinamide with EGFR-TKI: 1. gefitinib (250mg tab) or erlotinib (150mg tab) - per oral, once a day 2. nicotinamide (500mg tab) - per oral, twice a day, until the event or censoring occurs
Receives: Drug: Nicotinamide
PlaceboPlacebo comparatorPlacebo tablet with EGFR-TKI: 1. gefitinib (250mg tab) or erlotinib (150mg tab) - per oral, once a day 2. placebo tablet - per oral, twice a day, until the event or censoring occurs
Receives: Drug: Nicotinamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Hazard ratio (PFS) of the nicotinamide arm to the placebo arm

    Cox regression analysis

    Measured: two year

Secondary outcomes (3)

  1. Response rate

    chi-square test of complete response and partial response (RECIST 1.1)

    Measured: two year

  2. Difference in quality of life between the nicotinamide arm and the placebo arm

    measured by the cancer-related QOL questionaire response (questioned at each visit)

    Measured: two year

  3. Overall survival

    Cox regression analysis

    Measured: two year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Apr 2015 (estimated)
  2. Study startMar 2015
  3. Primary completionMar 2020 (estimated)
  4. Study completionJun 2020 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
110 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02416739
Sponsor's protocol ID
Amina-X-002
Status last verified
Jan 2020
First submitted
3 Apr 2015
Last updated
27 Jan 2020
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

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. doi: 10.1016/j.bbrc.2003.12.079.

    PubMed 14715269

  • 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. doi: 10.1016/s0092-8674(02)00690-6.

    PubMed 11955451

  • 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. doi: 10.1016/j.molcel.2005.02.022.

    PubMed 15780941

  • 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.

    PubMed 18995842

  • 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.

    PubMed 24229708

  • 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. doi: 10.1007/s12253-011-9485-5. Epub 2012 Jun 24.

    PubMed 22729835

  • 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.

    PubMed 21511279

  • 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.

    PubMed 21503886

  • Surjana D, Halliday GM, Damian DL. Role of nicotinamide in DNA damage, mutagenesis, and DNA repair. J Nucleic Acids. 2010 Jul 25;2010:157591. doi: 10.4061/2010/157591.

    PubMed 20725615

  • 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.

    PubMed 20371709

  • McCarthy AR, Sachweh MC, Higgins M, Campbell J, Drummond CJ, van Leeuwen IM, Pirrie L, Ladds MJ, Westwood NJ, Lain S. Tenovin-D3, a novel small-molecule inhibitor of sirtuin SirT2, increases p21 (CDKN1A) expression in a p53-independent manner. Mol Cancer Ther. 2013 Apr;12(4):352-60. doi: 10.1158/1535-7163.MCT-12-0900. Epub 2013 Jan 15.

    PubMed 23322738

  • 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. doi: 10.1007/s001250051536.

    PubMed 11126400

  • Gale EA, Bingley PJ, Emmett CL, Collier T; European Nicotinamide Diabetes Intervention Trial (ENDIT) Group. European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes. Lancet. 2004 Mar 20;363(9413):925-31. doi: 10.1016/S0140-6736(04)15786-3.

    PubMed 15043959

  • Petley A, Macklin B, Renwick AG, Wilkin TJ. The pharmacokinetics of nicotinamide in humans and rodents. Diabetes. 1995 Feb;44(2):152-5. doi: 10.2337/diab.44.2.152.

    PubMed 7859933

  • Schoenfeld DA. Sample-size formula for the proportional-hazards regression model. Biometrics. 1983 Jun;39(2):499-503.

    PubMed 6354290

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Nicotinamide in people with Non-Small-Cell Lung Carcinoma, run by Il Yeong Park, Ph.D. at 1 site in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hazard ratio (PFS) of the nicotinamide arm to the placebo arm (time frame: two year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02416739, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2020.

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