Curcumin in Reducing Joint Pain in Breast Cancer Survivors With Aromatase Inhibitor-Induced Joint Disease

Breast Cancer Clinical Trial

Official title:

Curcumin for Breast Cancer Survivors With Aromatase Inhibitor-Induced Joint Arthropathy - A Randomized, Double-Blinded, Controlled Pilot Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03865992
• Other study ID #: 18432
• Secondary ID: NCI-2018-0378718
• Status: Active, not recruiting
• Phase: N/A
• Start date: March 4, 2019
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase I trial studies how well curcumin works in reducing joint pain in patients who are breast cancer survivors and have joint disease caused by treatment with aromatase inhibitors. Curcumin is an ingredient of turmeric, a plant in the ginger family, which is commonly used in curries and South Asian and Middle Eastern cooking, and may decrease joint pain in patients with arthritis from other conditions (such as osteoarthritis and rheumatoid arthritis).

Description:

PRIMARY OBJECTIVES:

I. To evaluate the feasibility of using Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES) scores to detect changes in AI-induced symptoms and well-being in postmenopausal women with breast cancer at 3 months of nanoemulsion curcumin (NEC) vs placebo

SECONDARY OBJECTIVES:

I. To evaluate Disabilities of the Arm, Shoulder and Hand (DASH), Brief Pain Inventory, and Geriatric Assessment as secondary tools for monitoring AI-induced symptoms and well-being II. To evaluate adherence to a regimen of NEC vs placebo by postmenopausal women experiencing joint arthropathy induced by aromatase inhibitor therapy III. To obtain preliminary data regarding function in women with AI induced arthropathy (IA) by monitoring grip strength at 0 and 3 months of NEC versus placebo IV. To conduct exploratory analyses of blood based biomarkers in postmenopausal women with AI-induced arthropathy taking NEC vs placebo.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive nanoemulsion curcumin orally (PO) twice daily (BID) for up to 3 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO BID for up to 3 months in the absence of disease progression or unacceptable toxicity.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 42
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Women with histologically confirmed primary invasive adenocarcinoma of the breast, stages I-IIIA

• Estrogen-receptor positive (ER+) and/or progesterone-receptor positive (PR+) breast cancer

• Completion of definitive surgery with mastectomy or breast conserving therapy

• Postmenopausal (no menses >= 12 months) or on ovarian suppression in order to take AIs

• Currently taking an Food and Drug Administration (FDA) approved third-generation aromatase inhibitor (e.g., anastrozole [Arimidex], letrozole [Femara], or exemestane [Aromasin]) for >= 90 days prior to registration with plans to continue for >= 90 days after registration

• Clinical symptoms of joint pain for at least 3 months prior to study entry that started or increased with AI therapy with Brief Pain Inventory (BPI) Worst Pain score >= 4 (verbal response to BPI question 3 regarding the worst pain in the past 24 hours as 0 "no pain" to 10 "pain as bad as you can imagine")

Exclusion Criteria:

• Prior malignancy =< 5 years except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, ductal carcinoma in situ of the breast or adequately treated stage I or II cancer from which the patient is currently in complete remission

• History of a bleeding tendency or current use of coumadin or other anticoagulants

• Current or previous history of anemia

• Current autoimmune, liver, hematopoietic, cardiac, or renal disease

• Current viral, bacterial, atypical or fungal infections of any organ system

• Concurrent use of immunosuppressant medications

• Concurrent use of medications known to inhibit or induce hepatic enzyme CYP 3A4 (e.g. ketoconazole, macrolide antibiotics, barbiturates)

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements

• Bone fracture or surgery of the affected joints, within 180 days of study entry

• Medical therapy, alternative therapy, or physical therapy for joint pain/stiffness =< 30 days of study entry

• Intra-articular steroids =< 90 days of study entry or oral/intramuscular corticosteroids < 30 days of entry

• Use of analgesics (e.g., opiates, tramadol with the exception of nonsteroidal anti-inflammatory drugs [NSAIDs] and acetaminophen) within 14 days prior to registration, or at any time during the 3-month study period

• Chronic use of any herbal or dietary supplement containing curcumin or curcuminoids =< 3 months of study entry or any other supplements that might interact with NEC (e.g. St. John's Wort)

• Known sensitivity or allergy to turmeric spices or curry

Related Conditions & MeSH terms

• Arthralgia
• Breast Cancer
• Breast Neoplasms
• Joint Pain

Intervention

Dietary Supplement:
• Curcumin
Given capsules for oral administration

Other:
• Placebo
Given capsules for oral administration
• Nanoemulsion
Given nanoemulsion curcumin PO
• Quality-of-Life Assessment
Ancillary studies

Behavioral:
• Questionnaire
Ancillary studies

Locations

Country	Name	City	State
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	City of Hope Medical Center	Duarte	California
United States	City of Hope Rancho Cucamonga	Rancho Cucamonga	California
United States	City of Hope South Pasadena	South Pasadena	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Joint symptoms occurrence	The study will use logistic regression models to compare the occurrence of moderate to severe joint symptoms during the 3 month period between the two study groups, with potential covariates including geriatric assessment (GA), age, body mass index, baseline pain scores (0 month), prior chemotherapy e.g. taxanes, time to menopause/ovarian suppression. Summary statistics will be generated using the data obtained from the T0 and T3 study visits where grip strength dynamometry completed. Temporal as well as other relevant correlations between the data and the validated assessment scores will be determined.	Up to 3 months
Other	Blood based biomarker analysis	The study will explore the relationship between specific inflammatory blood markers, grip strength, and the joint symptoms evaluated by the patient reported outcome measures. The relationship between plasma curcumin and these measures will also be evaluated. Scatter plots and correlation coefficients (either Pearson or Spearman) will be used to summarize their pair wise relation. The differences between the treatment and placebo in terms of these measures will also be reported using numerical summaries and graphic plots.	Up to 3 months
Other	Adherence rates	Adherence rates will be examined using pill counts each month and patient recorded daily logs. Plasma curcumin will be compared to daily logs and pill count data as another potential measure of adherence.	Up to 3 months
Primary	Changes in aromatase inhibitor-induced symptoms and overall wellbeing in postmenopausal women on aromatase inhibitor therapy	The study will assess the feasibility of using the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES) to detect changes in aromatase inhibitor (AI)-induced symptoms and well-being in postmenopausal women with breast cancer randomized to 3 months of nanoemulsion curcumin (NEC) versus (vs) placebo capsules.	Up to 3 months
Primary	Change in Brief Pain Inventory (BPI) pain score	The scores obtained from the Disabilities of the Arm, Shoulder and Hand (DASH) and BPI, and FACT-ES assessments will be plotted over time for each arm. The agreement between these instruments will be evaluated using Altman and Bland plot after proper data transformation.	Baseline up to 3 months
Secondary	Incidence of adverse events	Adverse events will be characterized using the descriptions and grading scales found in the most recent version of the Common Terminology Criteria for Adverse Events version 5.0.	Up to 30 days post study-drug assessment
Secondary	Change in FACT-ES score	The scores obtained from the BPI, DASH, and FACT-ES assessments will be plotted over time for each arm. The agreement between these instruments will be evaluated using Altman and Bland plot after proper data transformation	Baseline up to 3 months
Secondary	Change in DASH score	The scores obtained from the BPI, DASH, and FACT-ES assessments will be plotted over time for each arm. The agreement between these instruments will be evaluated using Altman and Bland plot after proper data transformation.	Baseline up to 3 months