A Open-label Prospective Cohort Trial of Curcumin Plus Tyrosine Kinase Inhibitors (TKI) for EGFR -Mutant Advanced NSCLC

Study Overview
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Brief Summary
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The purpose of this study is is to assess the safety and tolerability of curcumin in combination with EGFR-TKIs in selected patients with advanced non-resectable mutant EGFR NSCLC.

Detailed Description
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This is a phase 1 open prospective cohort study to assess the safety and feasibility of using curcumin in conjunction with an EGFR-TKI in patients with advanced NSCLC. The investigators will use an enhanced bioavailable formulation of curcumin (CURCUViva TM at 80 mg/ 1 capsule per day) approved and licensed by Health Canada (NPN 80027414) that has been shown to have 2-3 times higher curcumin concentration in the blood as compared to previous clinical trials. As primary objective, the investigators will recruit 20 patients for a duration of 8 weeks to monitor adverse effects according to the the National Cancer Institute Common Terminology Criteria.Exploratory objectives would include assessing changes in health-related quality of life using the standardized FACT-L questionnaire and evaluating anti-inflammatory properties of curcumin by measuring CRP. If tolerable safety data is obtained, an expanded phase II trial will be designed.

Official Title
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A Phase 1 Open-label Prospective Cohort Trial of Curcumin Plus Tyrosine Kinase Inhibitors for Epidermal Growth Factor Receptor (EGFR)-Mutant Advanced Non-small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Dietary Supplement: CurcuVIVA™
* Drug: Tyrosine Kinase Inhibitor gefitinib (Iressa)
* Drug: Tyrosine Kinase Inhibitor erlotinib (Tarceva)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed or patients on treatment for histologically confirmed advanced EGFR-mutant NSCLC defined as unresectable stage 3A, stage 3B or stage 4. The EGFR mutation analysis must be performed prior to enrolment into the trial (i.e., before a patient is consented). Any EGFR mutation-positive result must be documented and the analysis for the mutation will be performed using the JGH local testing methodology. Receiving concurrent EGFR-TKI therapy. Eastern Cooperative Oncology Group (ECOG) Performance Score 0-3 Exclusion Criteria: Symptomatic brain metastases. Patients who are receiving any other investigational agents. Patients using other non-vitamin or mineral regular natural health product, which includes Chinese Herbs. Incapacity to understand and sign a written informed consent document in English/French. Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>CurcuVIVA™ (NPN 80027414) at a single dose of 80 mg PO daily without any dose escalation to be taken in conjunction with an EGFR-TKI therapy. CurcuVIVA™ is given in capsule forms. Unit strength of CurcuVIVA™ is equal to Turmeric Extract 25:1 348 mg (containing 80mg Longvida® Optimized Curcumin) Tyrosine Kinase Inhibitors: Gefitinib is a targeted therapy, given in a capsule form once daily. The daily dose is 250 mg . Erlotinib is a targeted therapy, given in a capsule form once daily. The daily dose is 150 mg . Study intervention is 8 weeks, following which the patients will continue taking their EGFR-TKI without curcumin until progression. The side effects of curcumin will be followed for another 8 weeks from the date of stopping curcumin. | Dietary Supplement: CurcuVIVA™<br>* 80 mg PO daily for 8 weeks with an option to reduce the dose based on individual tolerability<br>* Other names: Curcumin;Drug: Tyrosine Kinase Inhibitor gefitinib (Iressa)<br>* 250 mg PO daily until progression<br>* Other names: gefitinib (Iressa);Drug: Tyrosine Kinase Inhibitor erlotinib (Tarceva)<br>* 150 mg PO daily until progression<br>* Other names: erlotinib (Tarceva);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| feasibility assessed by: Willingness of patients to participate= Number of enrolled/Number of approached patients, | Feasibility will determine whether the use of curcumin is appropriate for further testing; and will be assessed by: Willingness of patients to participate= Number of enrolled/Number of approached patients, | 8 weeks | 
| feasibility assessed by follow-up rate= number of actual study visits/ total number of study visits | will by assessed by follow-up rate= number of actual study visits/ total number of study visits | 8 weeks | 
| feasibility Adherence/Compliance rate= Number of taken capsules/Total number of capsules | Adherence/Compliance rate= Number of taken capsules/Total number of capsules | 8 weeks | 
| feasibility Questionnaires completion rate= Number of completed questionnaires/Total number of questionnaires | Questionnaires completion rate= Number of completed questionnaires/Total number of questionnaires | 8 weeks | 
| safety number of side effects | Safety will be assessed by number of side effects | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate and compare the changes in health-related quality of life before and after | Patients' quality of life on curcumin treatment will be assessed by the FACT-L at the baseline, 4 weeks,8 weeks on concurrent curcumin and TKI and 8 weeks post-study. Clinically important difference in the score is considered 2 points. | 8 weeks | 
| To evaluate anti-inflammatory properties of Curcumin (assessed by measuring C-reactive protein) | anti-inflammatory effects of curcumin will be assessed by measuring C-reactive protein tests will be performed at baseline, 2, 4, 8 and 16 weeks into study. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TKI, curcumin, lung cancer