Description:
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.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
Amina-X-002
- NCT ID:
NCT02416739
Conditions
- Non-Small-Cell Lung Carcinoma
Interventions
Drug | Synonyms | Arms |
---|
Nicotinamide | Amina-X | Nicotinamide |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Nicotinamide | Experimental | 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 | |
Placebo | Placebo Comparator | 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 | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Hazard ratio (PFS) of the nicotinamide arm to the placebo arm |
Time Frame: | two year |
Safety Issue: | |
Description: | Cox regression analysis |
Secondary Outcome Measures
Measure: | Response rate |
Time Frame: | two year |
Safety Issue: | |
Description: | chi-square test of complete response and partial response (RECIST 1.1) |
Measure: | Difference in quality of life between the nicotinamide arm and the placebo arm |
Time Frame: | two year |
Safety Issue: | |
Description: | measured by the cancer-related QOL questionaire response (questioned at each visit) |
Measure: | Overall survival |
Time Frame: | two year |
Safety Issue: | |
Description: | Cox regression analysis |
Details
Phase: | Phase 2/Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Il Yeong Park, Ph.D. |
Trial Keywords
Last Updated
January 27, 2020