Phase II Trial to Modulate Intermediate Endpoint Biomarkers in Former and Current Smokers

Study Overview
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Brief Summary
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The purpose of this study is to find out if an investigational combination drug called Lovaza (made with fish oils)+Curcumin C3 Complex (made from a root called curcumin) can help reduce the size of lung nodules. Researchers also want to find out if the combination of Lovaza+Curcumin C3 Complex is safe and tolerable.

Official Title
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Phase II Trial of Investigational Agents to Modulate Intermediate Endpoint Biomarkers, Including Pulmonary Nodules, in Former and Current Smokers

Conditions
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Lung Diseases, Lung Cancer, Protection Against

Intervention / Treatment
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* Drug: Curcumin C3 complex®
* Drug: Lovaza®
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 55 years of age or older Former smokers and current enrolled in LDCT lung cancer screening or those who are detected using a regular CT, and have Lung-RADS 3 category lesion(s), that would get a 6 month f/u LDCT or regular CT based on Lung-RADS recommendations or former and current smokers enrolled in LDCT lung cancer screening, or regular CT and have Lung-RADS 2 category lesions with part-solid or non-solid lung nodule ≥4mm mean diameter detected during screening LDCT or regular 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 Status of less than or equal to 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 containing components of study agents. 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 Participants must have normal organ and marrow function Willing to use contraception during the intervention period of 6 months (males and females) Not pregnant or lactating nor planning to become pregnant or lactate during the 6 month study intervention period.. Exclusion Criteria: Invasive cancer diagnosis (excluding basal cell carcinoma or skin squamous cell carcinoma) diagnosed within the last 2 years Inability to undergo CT Newly diagnosed nodule meeting Lung-RADS 4 criteria Have taken doxycycline or tetracycline less than or equal to 2 weeks Females- pregnant or lactating (throughout the duration of intervention of 6 months) Unwilling to use effective form of birth control (Males and females) (throughout the duration of intervention of 6 months).

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Curcumin C3 complex® +Lovaza®<br>Group A: 4 grams Lovaza®, 2 grams twice a day (BID). 2 grams by mouth daily, AM and PM 8,000 mgs CUR Curcumin C3 complex® tablets, divided into 2 doses. 4 grams by mouth, twice a day, AM and PM. | Drug: Curcumin C3 complex®<br>* Groups A and B as outlined in study arm. Drug will be dispensed by investigational pharmacists and self-administered by the participants.<br>* Other names: Curcuminoid;Drug: Lovaza®<br>* Groups A and B as outlined in study arm. Drug will be dispensed by investigational pharmacists and self-administered by the participants.<br>* Other names: Omega-3-Acid Ethyl Esters;|
| Active Comparator: Curcumin C3 complex® +Lovaza® +Placebo<br>Group B: 2 grams Lovaza®, 1 gram twice a day, AM and PM. 4,000 mgs CUR Curcumin C3 complex® tablets, 2,000 mgs twice a day, AM and PM. 1 placebo capsule twice a day, AM and PM. | Drug: Curcumin C3 complex®<br>* Groups A and B as outlined in study arm. Drug will be dispensed by investigational pharmacists and self-administered by the participants.<br>* Other names: Curcuminoid;Drug: Lovaza®<br>* Groups A and B as outlined in study arm. Drug will be dispensed by investigational pharmacists and self-administered by the participants.<br>* Other names: Omega-3-Acid Ethyl Esters;Other: Placebo<br>* Groups B and Placebo as outlined in study arm. Drug will be dispensed by investigational pharmacists and self-administered by the participants.<br>* Other names: Pill with no drug or other active ingredients in it.;|
| Active Comparator: Placebo only<br>Placebo: Two matching placebo capsules twice a day (BID), taken by mouth, AM and PM | Other: Placebo<br>* Groups B and Placebo as outlined in study arm. Drug will be dispensed by investigational pharmacists and self-administered by the participants.<br>* Other names: Pill with no drug or other active ingredients in it.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Bronchial Nodule Size | Difference in the average change in bronchial nodule size from baseline to end of therapy at 6 months for each study arm. A lower size is taken to be the desired value for participants receiving study drug, assuming an increase in size for the placebo arm. | 6 months post treatment | 
| Rate of Nodules ≥4 mm | Number of nodules ≥4 mm per study arm, post treatment. | 6 months post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Adherence | Rate of participant adherence per study arm. Proof of adherence based on study team pill counts, participant diet logs and pill logs at end of study, vs. data collected at midpoint. | 6 months post treatment | 
| Rate of Treatment Related Adverse Events (AEs) | Safety of the combined agents (Curcumin C3 complex® + Lovaza®) at 2 dose arms vs. placebo as indicated by incidence of related adverse events and toxicities, monitored using Common Toxicity Criteria version 5.0. | Up to 30 days post treatment, approximately 7 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung RADS 3, Lung nodule, Lung cancer risk, Chemoprevention