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

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

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.

Study Overview

• Status: Unknown
• Conditions: Lung Cancer
• Intervention / Treatment: Dietary supplement: CurcuVIVA™; Drug: Tyrosine Kinase Inhibitor gefitinib (Iressa); Drug: Tyrosine Kinase Inhibitor erlotinib (Tarceva)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Victor Cohen, MD; Phone Number: 3877 514-340-8222; Email: vcohen@jgh.mcgill.ca
• Study Contact Backup: Name: Goulnar Kasymjanova, MD; Phone Number: 4312 514-340-8222; Email: gkasymja@jgh.mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Peter Brojge Lung Cancer Center, Jewish General Hospital
      • Contact: Goulnar Kasymjanova, MD; Phone Number: 4312 514-340-8222; Email: gkasymja@jgh.mcgill.ca
      • Contact: Victor Cohen, MD,CM, FRCPC; Phone Number: 3878 514-340-8222; Email: vcohen@jgh.mcgill.ca
      • Sub-Investigator: Khashayar Esfahani, MD
      • Sub-Investigator: Arif Awan, MD
      • Sub-Investigator: Thomas R Jagoe, MD
      • Sub-Investigator: Jason S Agulnik, MD
      • Sub-Investigator: David Small, MD
      • Sub-Investigator: Carmela Pepe, MD
      • Sub-Investigator: Lama Sakr, MD
      • Sub-Investigator: Goulnar Kasymjanova, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1; 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™; 80 mg PO daily for 8 weeks with an option to reduce the dose based on individual tolerability; Other Names: Curcumin; Drug: Tyrosine Kinase Inhibitor gefitinib (Iressa); 250 mg PO daily until progression; Other Names: gefitinib (Iressa); Drug: Tyrosine Kinase Inhibitor erlotinib (Tarceva); 150 mg PO daily until progression; Other Names: erlotinib (Tarceva)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Lady Davis Institute
• Collaborators: Jewish General Hospital
• Investigators: Principal Investigator: Victor Cohen, MD, Lady Davis Institute

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Anticipated): August 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: December 1, 2014
• First Submitted That Met QC Criteria: December 19, 2014
• First Posted (Estimate): December 22, 2014

Study Record Updates

• Last Update Posted (Estimate): September 2, 2015
• Last Update Submitted That Met QC Criteria: September 1, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: lung cancer; curcumin; TKI
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride; Gefitinib; Curcumin
• Other Study ID Numbers: JGH-14-149