Anticancer Activity of Nicotinamide on Lung Cancer

Sponsor

Il Yeong Park, Ph.D. (Other)

Overall Status

Unknown status

CT.gov ID

NCT02416739

Collaborator

(none)

110

Enrollment

Location

Arms

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief 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. The purpose of this study is to determine whether nicotinamide is also effective in the treatment of human lung cancer.

Condition or Disease	Intervention/Treatment	Phase
Non-Small-Cell Lung Carcinoma	Drug: Nicotinamide	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

110 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 1, 2015

Anticipated Primary Completion Date :

Mar 1, 2020

Anticipated Study Completion Date :

Jun 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nicotinamide Nicotinamide with EGFR-TKI: gefitinib (250mg tab) or erlotinib (150mg tab) - per oral, once a day nicotinamide (500mg tab) - per oral, twice a day, until the event or censoring occurs	Drug: Nicotinamide Nicotinamide (1g/day) or placebo treatment is added to the standard drug treatment (gefitinib or erlotinib) to EGFR mutated NSCLC patients Other Names: Amina-X
Placebo Comparator: Placebo Placebo tablet with EGFR-TKI: gefitinib (250mg tab) or erlotinib (150mg tab) - per oral, once a day placebo tablet - per oral, twice a day, until the event or censoring occurs	Drug: Nicotinamide Nicotinamide (1g/day) or placebo treatment is added to the standard drug treatment (gefitinib or erlotinib) to EGFR mutated NSCLC patients Other Names: Amina-X

Arm

Intervention/Treatment

Experimental: Nicotinamide

Nicotinamide with EGFR-TKI: gefitinib (250mg tab) or erlotinib (150mg tab) - per oral, once a day nicotinamide (500mg tab) - per oral, twice a day, until the event or censoring occurs

Drug: Nicotinamide

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

Other Names:

Amina-X

Placebo Comparator: Placebo

Placebo tablet with EGFR-TKI: gefitinib (250mg tab) or erlotinib (150mg tab) - per oral, once a day placebo tablet - per oral, twice a day, until the event or censoring occurs

Drug: Nicotinamide

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

Other Names:

Amina-X

Outcome Measures

Primary Outcome Measures

Hazard ratio (PFS) of the nicotinamide arm to the placebo arm [two year]
Cox regression analysis

Secondary Outcome Measures

Response rate [two year]
chi-square test of complete response and partial response (RECIST 1.1)
Difference in quality of life between the nicotinamide arm and the placebo arm [two year]
measured by the cancer-related QOL questionaire response (questioned at each visit)
Overall survival [two year]
Cox regression analysis

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 previously
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