Curcumin and Piperine in Reducing Inflammation for Ureteral Stent-Induced Symptoms in Patients With Cancer

Study Overview
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Brief Summary
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This pilot phase I trial studies the side effects and best dose of curcumin when given together with piperine (piperine extract [standardized]) in reducing inflammation for ureteral stent-induced symptoms in patients with cancer. Curcumin is a spice similar to turmeric and works by decreasing the chemical moderators that produce inflammation in the body. Piperine is pepper and works by increasing the amount of curcumin available in the body when taken with curcumin. Giving curcumin together with piperine may reduce inflammation and discomfort from a ureteric stent in older patients with cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To conduct a dose-escalation study with curcumin and piperine to derive a safe, optimal biological dose of this combination in cancer patients. SECONDARY OBJECTIVES: I. To describe the grade 2+ toxicities associated with curcumin and piperine. II. To evaluate quality of life associated with this combination by means of the Mayo Modified Urinary Stent Symptom Questionnaire (USSQ). TERTIARY OBJECTIVES: I. To characterize the change in urinary prostaglandin E2 concentrations that occur at baseline and then after one week of curcumin + piperine. OUTLINE: This is a dose-escalation study of curcumin. Patients receive curcumin orally (PO) twice daily (BID) or thrice daily (TID) and piperine extract (standardized) PO on days 1-7 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 1 month.

Official Title
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Phase 1 Pilot Study of Curcumin and Piperine to Derive a Safe, Optimal Biologic Dose for Ureteral Stent-Induced Symptoms in Cancer Patients

Conditions
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Urinary Urgency, Bladder Spasm, Malignant Neoplasm, Pain

Intervention / Treatment
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* Drug: Curcumin
* Other: Laboratory Biomarker Analysis
* Dietary Supplement: Piperine Extract (Standardized)
* Other: Quality-of-Life Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ureteral stent in place at study registration Patient reports pain, spasms, or urgency symptoms after stent placement, which are thought to be unrelated to other causes as per the patient or healthcare provider or both (documentation in the medical record is unnecessary) Ability to complete English language questionnaires by themselves or with assistance After the week-long study treatment, participants must be willing to return to the enrolling institution for a follow-up visit Willingness to provide mandatory 24 hour urine collection samples for research purposes Able to swallow supplements Patient must have either a history of cancer or active cancer Registration >= 7 days after placement of a new stent or >= 3 days after a stent exchange Willingness to refrain from grapefruit juice for 7 days prior to and for 7 days during the study Exclusion Criteria: Receiving warfarin at registration Active cholecystitis Requires treatment with non-steroidal anti-inflammatory agents that cannot be stopped for one week during study participation Taking any of the following drugs at the time of study participation: epidermal growth factor receptor inhibitor, topoisomerase 1 inhibitor (camptothecin, irinotecan); buspirone, benzodiazepines, zolpidem, calcium channel blockers (such as felodipine, nifedipine, verapamil); digoxin or quinidine; codeine or fentanyl; phenytoin, propranolol, rifampin, or theophylline History of alcohol abuse

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Supportive care (curcumin, piperine)<br>Patients receive curcumin PO BID or TID and piperine extract (standardized) PO on days 1-7 in the absence of disease progression or unacceptable toxicity. | Drug: Curcumin<br>* Given PO<br>* Other names: Turmeric Yellow;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Dietary Supplement: Piperine Extract (Standardized)<br>* Given PO<br>* Other names: Standardized Piperine Extract;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events, using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 | Examined in an exploratory and hypothesis-generating fashion. The number and severity of all adverse events (overall, by dose-level, and by tumor type) will be tabulated and summarized in this patient population. The grade 2+ adverse events will also be described and summarized in a similar fashion. | Up to 1 month post-treatment | 
| Maximum tolerated dose (MTD) of curcumin in combination with piperine | The MTD of curcumin in combination with piperine is defined as the highest safely tolerated dose level where at most 1 out of 6 patients experience a dose limiting toxicity (DLT) with the next higher dose having at least 2 patients out of a maximum of 6 patients experiencing a DLT. DLT will be assessed using Common Terminology Criteria for Adverse Events version 4.0. Examined in an exploratory and hypothesis-generating fashion. | 7 days | 
| Optimal biologically active dose for curcumin in combination with piperine extract (standardized) | Examined in an exploratory and hypothesis-generating fashion. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in quality of life (QOL) by means of the USSQ | Reported descriptively. Graphical methods and descriptive statistics will be used to describe the QOL data at baseline and after treatment. Change in QOL from baseline will be assessed via the paired t-test or non-parametric equivalent (Wilcoxon Signed-Rank test). The questions from the USSQ will be summarized descriptively via frequency tables. | Baseline to 7 days |