Fish Oil and Curcumin in Preventing Lung Nodules from Growing Larger in Former Smokers
- Former smokers enrolled in LDCT lung cancer screening, and have Lung-RADS 3 category lesion(s), that would get a 6 month follow up (f/u) LDCT based on Lung-RADS recommendations. Former smokers enrolled in LDCT lung cancer screening, and have Lung-RADS 2 category lesions with persistent or slowly increasing part-solid or non-solid lung nodule > 4 mm mean diameter detected by two serial yearly screening low dose CT scans.
- History of cigarette smoking with >= 20 pack years.
- All current smokers should accept to receive smoking cessation.
- Eastern Cooperative Oncology Group (ECOG) performance score of =< 1.
- Able to swallow study pills.
- Able to undergo CT.
- Not allergic to components of study agents.
- Willing to discontinue current vitamin/mineral supplement use and substitute with a standard multivitamin supplement provided for the study.
- Willing to comply with proposed visit and treatment schedule.
- Able to understand and willing to sign a written informed consent document.
- Subjects with stage I-II invasive malignancies that were diagnosed more than 2 years prior to randomization and have been treated curatively are allowed as long as all treatment is completed at least 24 months prior to randomization.
- Complete blood count (CBC)- no clinically significant findings.
- Complete metabolic panel (CMP)- no clinically significant findings.
- PT/PTT- within normal institutional limits (10.2-12.9 sec)/(2.0-3.0).
- LDH- equal to or below the upper limit of normal (135-225 u/l).
- Serum creatinine < 1.5 mg/dl or measured creatinine clearance 60 cc/min.
- Negative urine human chorionic gonadotropin (HCG) (females-premenopausal).
- Willing to use contraception during the intervention period of 6 months (males and females). * Reliable methods of contraception include barrier hormonal and non-hormonal contraception, intra-uterine device (IUD), implant, vasectomy (> 3 months), and tubal ligation.
- Not pregnant or lactating nor planning to become pregnant or lactate during the 6 month study intervention period.
- History of lung cancer or invasive malignancy (with the exclusion of basal cell carcinoma or skin squamous cell carcinoma) diagnosed during the last 2 years before randomization.
- Inability to undergo CT.
- Newly diagnosed nodule meeting Lung-RADS 4 criteria.
- Have taken doxycycline or tetracycline =< 2 weeks.
I. Effectiveness of the combination of curcumin/demethoxycurcumin/bisdemethoxy curcumin-containing supplement (Curcumin C3 complex) + Lovaza (omega-3-acid ethyl esters) at 2 dose arms versus (vs.) placebo for 6 months to asymptomatic former smokers with lung nodules (high risk cohort screened and followed using low dose computed tomography [LDCT] or by using standard computed tomography [CT]), as indicated by:
Ia. Change in size of CT-detected lung nodules.
Ib. Number of nodules >= 4 mm, and lung nodule density of partially solid and non-solid lung nodules between the treatment and placebo arms.
I. Safety of the combined agents (Curcumin C3 complex + Lovaza [omega-3-acid ethyl esters]) at these 2 dose arms vs. placebo as indicated by incidence of adverse events and toxicities, monitored using Common Toxicity Criteria version 5.0, safety markers (complete blood count [CBC] & complete metabolic profile [CMP], lactate dehydrogenase [LDH], prothrombin time [PT]/partial thromboplastin time [PTT]) at baseline, midpoint, and end of intervention.
II. Bioavailability of the combination agents in the 2 dose arms vs. placebo, we will measure change in curcumin and its metabolites in plasma as well as plasma n-3 Index at baseline, midpoint, and at the end of treatment.
III. Adherence and acceptability of the combination agents at the 2 dose arms vs. placebo, we will conduct pill counts, collect diet and pill logs at baseline, midpoint and at the end of intervention.
IV. Effect of the combination agents (Curcumin C3 complex + Lovaza [omega-3-acid ethyl esters]) at the 2 dose arms vs. placebo as indicated by modulation of other intermediate endpoint biomarkers (IEBs) including: (a) inflammation- associated chemokines and cytokines (b) pro-resolving lipid mediators (c) targeted pathways NF-kappaB and (d) correlation of these findings with modulation of size of lung nodules.
OUTLINE: Patients are randomized to 1 of 3 groups.
GROUP A: Patients receive omega-3-acid ethyl esters orally (PO) twice daily (BID) and Curcumin C3 complex PO BID for 6 months.
GROUP B: Patients receive omega-3-acid ethyl esters PO BID, Curcumin C3 complex PO BID, and placebo PO BID for 6 months.
GROUP C: Patients receive placebo PO BID for 6 months.
After completion of study, patients are followed up at 7 days.
Trial Phase Phase II
Trial Type Prevention
Moffitt Cancer Center
Nagi B. Kumar
- Primary ID MCC-19622
- Secondary IDs NCI-2019-00376, 8JK03
- Clinicaltrials.gov ID NCT03598309