Skin and Connective Tissue Diseases

All Conditions

Neoplasms

Wounds and Injuries

Dermatitis

Breast Neoplasms

Radiodermatitis

Breast Diseases

Skin Diseases

Radiation Injuries

Anti-Inflammatory Agents

Antineoplastic Agents

Antirheumatic Agents

Analgesics

All Drugs and Chemicals

Curcumin

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Enzyme Inhibitors

Patients take 2.0 grams curcumin (four 500mg capsules) three times daily by mouth for prescribed course of radiation treatment (\~4-7 weeks).

Patients take 2.0 grams placebo (four 500mg capsules) three times daily by mouth for prescribed course of radiation treatment (\~4-7 weeks).

Patients take 2.0 grams curcumin (four 500mg capsules) three times daily by mouth for prescribed course of radiation treatment (\~4-7 weeks)

Curcumin C3 Complex

Patients take 2.0 grams placebo (four 500mg capsules) three times daily by mouth for prescribed course of radiation treatment (\~4-7 weeks)

Placebo

Julie L Ryan, PhD, MPH

Alice P Pentland, MD

Marilyn Ling, MD

Ionizing radiation is a toxic agent and widely accepted form of treatment for various types of cancer. Despite advances in medical technology, radiation therapy still causes severe early and late skin effects. Radiation-induced dermatitis occurs in approximately 80% of patients. Important consequences of radiation-induced dermatitis include impairment of the quality of a patient's life due to pain and premature interruption of radiation treatment, which in turn, may be impair good local control of disease. The biological pathways responsible for acute radiation-induced dermatitis remain unclear. Currently, there is no standard treatment for the prevention of radiation-induced dermatitis with demonstrated effectiveness. The aim of this randomized, double-blind, placebo-controlled pilot study is to assess the effectiveness of curcumin for the prevention of acute radiation-induced dermatitis during postoperative radiotherapy for breast cancer. We hypothesize that curcumin, a natural phenolic compound found in both turmeric and curry powders, can prevent or alleviate radiation-induced skin reactions in breast cancer patients receiving radiotherapy.

Specifically, this clinical pilot study will develop data necessary to calculate a sample size for a larger study to be conducted through the National Cancer Institute (NCI) Community Clinical Oncology Program (CCOP) mechanism. Specifically, this pilot project will investigate: 1) if curcumin can prevent or alleviate radiation-induced skin reactions in cancer patients receiving radiotherapy and 2) if skin pigmentation, as well as pain and psychophysiological factors, can predict the severity of radiation-induced dermatitis. Potential future research studies may be conducted to identify the biological mechanisms involved in radiation-induced dermatitis and the radioprotective function of curcumin.

Curcumin for the Prevention of Radiation-induced Dermatitis in Breast Cancer Patients

The severity of radiation dermatitis was measured using the Radiation Dermatitis Severity (RDS)Scale which ranges from 0.0 to 4.0 with increments of 0.5. The RDS scale is a revised form of the NIH Common Toxicity Criteria to account for color and subtle texture changes in the skin. The worst dermatitis (i.e., highest RDS score) at the end of treatment was used for the primary analysis of severity of radiation dermatitis in each treatment group. Additionally, we performed repeated measure analyses to examine the severity of dermatitis over time in each arm.

The presence of moist desquamation at the end of radiation treatment was examined between curcumin and placebo treatment groups. We compared the number of participants (or percentage) with moist desquamation between each treatment group.

Redness at radiation treatment site was measured using a CR-400 Colorimeter (Konica Minolta). The colorimeter uses the L\*a\*b\* color scale. We used a\* values (redness) which range from 0.0 to 20.0. The lower the number value, the lower amount of redness. Therefore, high number values represent large amounts of redness.

The McGill Pain Questionnaire-Short Form (MPQ-SF) was used to determine the participants pain at treatment site. The MPQ-SF contains three subscales: affective pain, sensory pain, and perceived pain. This outcome measure compared the total pain score (range 0 to 50)and subscale scores (sensory subscale range 0 to 33; affective subscale range 0 to 12; perceived pain subscale 0 to 5) at the end of radiation therapy between the two treatment arms.

University of Rochester

Assistant Professor

Total

Age, Categorical

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

The primary limitation of this clinical study is the small sample size. This study was a pilot trial to generate an effect and sample size for a larger confirmatory trial. We accrued patients to this study until we had 30 fully evaluable patients.

Julie L Ryan, PhD, MPH (PI)

Hypothesis: The mean RDS for curcumin group is significantly different (i.e., lower) than mean RDS of placebo group at end of radiation treatment.

Patients take 2.0 grams curcumin (four 500mg capsules) three times daily by mouth for prescribed course of radiation treatment (RT) (\~4-7 weeks).

Patients take 2.0 grams placebo (four 500mg capsules) three times daily by mouth for prescribed course of radiation treatment (RT)(\~4-7 weeks).

We used all 30 participants that fully completed the trial in all of our analyses.

Severity of Dermatitis in Radiation Treatment Site in Breast Cancer Patients

Hypothesis: The presence of moist desquamation significantly differed between the curcumin group and the placebo group.

All 30 participants who completed the trial were used in all analyses.

Moist Desquamation at Radiation Treatment Site

Hypothesis: There is a significant difference in mean redness (i.e., mean a\* number value) between the curcumin and placebo groups.

The 30 participants that fullt completed the trial were used in these analyses.

Redness at Radiation Treatment Site

Hypothesis: There is a significant difference in mean MPQ pain scores between the curcumin and placebo groups.

Hypothesis: There is a significant difference in mean sensory subscale pain scores between curcumin and placebo groups.

Hypohesis: There is a signifcant difference in affective subscale pain scores between curcumin and placebo groups.

Hypothesis: There is a significant difference in mean perceived pain scores between curcumin and placebo groups.

MPQ Total Score

Sensory Pain Subscale

Affective Pain Subscale

Perceived Pain Intensity

All 30 participants that fully completed the trial were used in these analyses.

Pain at Radiation Treatment Site

Overall Study

Infections

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Immune System Diseases

Rare Diseases

Communicable Diseases

Uterine Cervical Diseases

Acquired Immunodeficiency Syndrome

HIV Infections

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Cervical Intraepithelial Neoplasia

Herbal and Botanical

Turmeric extract

Turmeric

Participants in this arm will use 2000 mg of intravaginal curcumin once a week for 20 weeks

Participants in this arm will use 2000 mg of intravaginal placebo once a week for 20 weeks

Curcumin (Curcumin C3 Complex prepared by Sabinsa Corporation), a constituent of the spice turmeric, is considered to be a low-toxicity, dietary-derived agent with chemopreventative and therapeutic benefits.

Study participants will be instructed to insert four 500 mg (2000 mg total) curcumin capsules once a week (excluding days when they are on their menses) for 20 weeks. Participants will insert capsules using the vaginal applicator while lying on their back with their knees bent. Participants will be instructed to gently insert the capsules into the vagina as far as they will go comfortably, similar to a tampon insertion or other common intravaginal drugs.

Cervical cytology and HPV testing will be performed at baseline and 6 months after the baseline visit. If cervical cytology or HPV testing is abnormal at 6 months, a colposcopy with biopsies will be performed. All samples will be used to analyze for the study outcomes.

Study participants randomized to the placebo arm will insert four 500 mg (2000 mg total) of the placebo (gelatin) capsules once a week (excluding days when they are on their menses) for 20 weeks. Participants will insert the capsules using the vaginal applicator while lying on their back with their knees bent. Participants will be instructed to gently insert the capsules into the vagina as far as they will go comfortably, similar to a tampon insertion or other common intravaginal drugs.

Cervical cytology and HPV testing will be performed at baseline and 6 months after the baseline visit. If cervical cytology or HPV testing is abnormal at 6 months, a colposcopy with biopsies will be performed. All samples will be used to analyze for the study outcomes.

Lisa Flowers, MD

The purpose of this study is to see if curcumin can suppress HPV infection in women with low-grade squamous intraepithelial lesions (LSIL) disease or treated high-grade squamous intraepithelial lesions (HSIL) disease. This study plans to explore the effect of curcumin as a potential medical treatment in HIV-uninfected and infected women with mild precancerous lesions of the cervix or recently treated high-grade precancerous lesions at risk for persistent HPV infection. About 200 women with low-grade precancerous lesions of the cervix or recently treated high-grade precancerous lesions will be enrolled to either insert 2000 mg of curcumin capsules in their vagina once a week or placebo after undergoing colposcopy or loop electrosurgical excision procedure (LEEP). They will have a repeat visit in 6 months where they will undergo a Pap smear and HPV test to determine if there are higher rates of HPV clearance after curcumin administration. If HPV is present or the Pap smear is abnormal, patients will then undergo colposcopic examination to evaluate cervical histology.

Cervical cancer is the third most common cancer worldwide. The causative agent responsible for cervical cancer is the persistent infection with oncogenic Human Papillomavirus (HPV). Rates of cervical cancer and HPV infection are increased particularly in HIV-infected women due to immunosuppression with cervical cancer categorized as an AIDS-defining diagnosis. Despite the promise of HPV vaccine in the prevention of cervical cancer, the widespread availability of this vaccine is limited due to cost and accessibility. Therefore, prevention strategies to reduce the risk of cervical cancer after HPV exposure entail treatment at the premalignant state, including low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL), along with the eradication of HPV infection. There is a desperate need for an inexpensive, non-invasive alternative method to treat these premalignant cervical lesions and potentially suppress HPV infection.

Curcumin, an extract from turmeric, a popular culinary spice, has been used in traditional Indian medicine for its anti-inflammatory and anti-infectious properties. Recent studies have shown the potential effect of curcumin to reduce tumors and precancerous lesions in animal and human cancer cells. It is postulated that curcumin achieves its effect on cancer cells by modulating different cellular pathways as well as altering HPV effect on tissue cells.

The purpose of this study is to see if curcumin can suppress HPV infection in women with LSIL disease or treated HSIL disease. The researchers plan to explore the effect of curcumin as a potential medical treatment in HIV-uninfected and infected women with mild precancerous lesions of the cervix or recently treated high-grade precancerous lesions at risk for persistent HPV infection. About 200 women with low-grade precancerous lesions of the cervix or recently treated high-grade precancerous lesions will be enrolled to either insert 2000 mg of curcumin capsules in their vagina once a week or placebo after undergoing colposcopy or LEEP. They will have a repeat visit in 6 months where they will undergo a Pap smear and HPV test to determine if there are higher rates of HPV clearance after curcumin administration. If HPV is present or the Pap smear is abnormal, patients will then undergo colposcopic examination to evaluate cervical histology.

Topical Curcumin for HPV Related Cervical Disease

An Investigation in the Use of Curcumin Topical Herbal Agent for the Treatment of Cervical Intraepithelial Neoplasia

Individual participant data that underlie the published results will be made available for sharing after deidentification.

The treatment will be considered tolerable if 25% or fewer of participants discontinue the study early.

HPV clearance, assessed as the number of participants with undetectable high-risk HPV mRNA levels in the standard monolayer Pap test (ThinPrep), at 6 months will be compared between the curcumin and placebo study arms.

Disease recurrence will be assessed either cytologic or histologic abnormality at 6 months. Rates of disease recurrence will be compared between study arms in HIV-uninfected and infected women.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Curcumin for the Prevention of Radiation-induced Dermatitis in Breast Cancer Patients	NCT01042938	Breast Cancer	Curcumin C3 Com... Placebo	21 Years -	University of Rochester
Curcumin for the Prevention of Radiation-induced Dermatitis in Breast Cancer Patients	NCT01042938	Breast Cancer	Curcumin C3 Com... Placebo	21 Years -	University of Rochester
Topical Curcumin for HPV Related Cervical Disease	NCT04266275	Neoplasm Cervix	Curcumin C3 Com... Placebo	21 Years -	Emory University
Curcumin for the Prevention of Radiation-induced Dermatitis in Breast Cancer Patients	NCT01042938	Breast Cancer	Curcumin C3 Com... Placebo	21 Years -	University of Rochester

Spots Global Cancer Trial Database for curcumin c3 complex