Study to See How Safe Curcumin is and How Well it Works When Used to Treat Mucositis in Patients Getting Chemotherapy

Study Overview
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Brief Summary
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Oral mucositis is a common side effect from cancer treatment. Patients receiving chemotherapy and radiotherapy can get very painful sores in their mouth that compromise nutrition and oral hygiene as well as increase risk for infection, and can last for weeks. Currently, the only treatment for mucositis is oral hygiene to try to support recovery. Curcumin (also known as Turmeric) is a frequently-used spice in India and Southeast Asia. Studies in cells and animals have shown that it can reduce the amount of bacteria and can prevent inflammation. In this study, the investigators want to learn if a mouthwash made with curcumin is safe for people to use and if it can help their mucositis.

Detailed Description
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This is a phase I/II study involving 2 parts; a dose escalation to determine the maximum tolerated dose (MTD) of curcumin and an expansion at the MTD. Oral mucositis is a common and often debilitating complication associated with cancer treatment. Treatment of mucositis is mainly supportive - oral hygiene is the means of treatment. Curcumin (Turmeric), a frequently-used spice in India and Southeast Asia, can reduce bacterial load and prevent inflammation in cultured epithelial cells and prevent chemotherapy- and radiotherapy-induced mucositis in animal models. The primary objective of this Phase I/II study is to determine the maximum tolerated dose (MTD) of oral curcumin in patients who have chemotherapy-induced mucositis. The secondary objectives of this study are to determine whether or not oral curcumin has an acceptable safety profile or impacts oral mucositis health outcomes.

Official Title
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A Phase I/II Study to Determine the Safety and Efficacy of Curcumin in Patients With Oral Mucositis Secondary to Chemotherapy

Conditions
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Mucositis

Intervention / Treatment
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* Drug: Curcumin-MTD
* Drug: Mouthwash-standard pharmacy preparation
* Drug: Curcumin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ grade 2 oral mucositis related to chemotherapy for cancer Ability to understand and the willingness to review and sign a written informed consent document. ≥ 18 years of age Willingness to use adequate contraception prior to study entry, for the duration of study participation and for 30 days after the last dose for women of child-bearing potential and men Exclusion Criteria: Current use of therapeutic doses of anticoagulants such as warfarin or antiplatelet agents (prophylactic doses and agents are acceptable) Biliary tract obstruction or cholelithiasis History of gastric or duodenal ulcers or hyperacidity syndromes AST or ALT > 2 x ULN Total bilirubin ≥ 2 x ULN INR > 1.5 Previous stem cell transplant (allogeneic or autologous) Preexisting oral disease, such as active oral infection, trauma to the oral mucosa or oral - ulceration prior to chemotherapy Known allergy/hypersensitivity to curcumin, yellow food coloring, or other members of the - Zingiberaceae (ginger) family Pregnant or breastfeeding

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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mouthwash-standard pharmacy preparation<br>Standard mouth wash preparation administered by ingested mouth rinse three times per day. The standard mouth rinse contains 40% Benadryl, 40% Maalox, and 20% of 1% Viscous Lidocaine. | Drug: Mouthwash-standard pharmacy preparation<br>* Standard mouth wash preparation administered by ingested mouth rinse three times per day. The standard mouth rinse contains 40% Benadryl, 40% Maalox, and 20% of 1% Viscous Lidocaine.<br>* Other names: no other name;|
| Experimental: Curcumin<br>Curcumin (BCM-95) administered by ingested mouth rinse three times per day. Subjects will be in this arm at the previously determine maximum tolerated dose (MTD). | Drug: Curcumin<br>* After maximum tolerated dose (MTD) is determined, MTD by ingested mouth wash three times per day for 4-6 weeks until mucositis is resolved, disease progression, or unacceptable toxicity develops.<br>* Other names: Tumeric;|
| Other: Curcumin-MTD<br>Curcumin (BCM-95) administered by ingested mouth rinse. A total of 12-15 subjects will be in this arm to determine maximum tolerated dose (MTD). There will be 3 participant at each of 4 does levels (0.33g, 1g, 2g, 3g) per rinse, three times daily for 4-6 weeks. (additional 3 subjects if a dose-limiting toxicity occurs) | Drug: Curcumin-MTD<br>* 0.33g-3g by ingested mouth wash three times per day for 4-6 weeks until unacceptable toxicity develops- to determine the maximum tolerated does (MTD).<br>* Other names: Tumeric;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious and Non-Serious Adverse Events | Number of Participants with Serious and Non-Serious Adverse Events. | reviewed weekly for 4 to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Toxicities Graded by Health Care Providers Using the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | NA - Protocol ended early after failing to enroll sufficiently. Only 6 subjects enrolled, 5 completed, 1 withdrew. Zero participants analyzed. | Baseline, weekly for 5 to 7 weeks | 
| Change in Subjective Patient Self-assessment of Pain. | NA - Protocol ended early after failing to enroll sufficiently. Only 6 subjects enrolled, 5 completed, 1 withdrew. Insufficient data to analyze | Baseline, weekly for 5 to 7 weeks | 
| Change in Subjective Patient Self- Assessment of Oral Mucositis Measured by the Common Terminology Criteria for Adverse Events (CTCAE) and World Health Organization's (WHO's) Oral Toxicity Scale (OTS) | NA - Protocol ended early after failing to enroll sufficiently. Only 6 subjects enrolled, 5 completed, 1 withdrew. Insufficient data to analyze | Baseline, weekly for 5 to 7 weeks | 
| Change in Health Providers Assessment of Oral Mucositis and Healing Time Measured by the Common Terminology Criteria for Adverse Events (CTCAE) and World Health Organization's (WHO's) Oral Toxicity Scale (OTS) | NA - Protocol ended early after failing to enroll sufficiently. Only 6 subjects enrolled, 5 completed, 1 withdrew. Insufficient data to analyze | Baseline, then weekly for 4 to 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mucositis, Neoplasms, CANCER, Curcumin, Drug Therapy, ANTINEOPLASTIC AGENTS