Clinical trial NCT02416739: Anticancer Activity of Nicotinamide on Lung Cancer
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Non-Small-Cell Lung Carcinoma
Keywords: EGFR mutated lung cancer
Lead sponsor: Chungbuk National University
Sponsor class: OTHER
First posted: 2015-04-15
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Hazard ratio (PFS) of the nicotinamide arm to the placebo arm
timeFrame: two year
Secondary outcomes:
measure: Response rate
timeFrame: two year
measure: Difference in quality of life between the nicotinamide arm and the placebo arm
timeFrame: two year
measure: Overall survival
timeFrame: two year
Other outcomes:
Locations:
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Chonnam
Study officials:
affiliation: Chungbuk National University
name: Il Yeong Park, PhD
role: STUDY_DIRECTOR
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