Phase II Study of Curcumin vs Placebo for Chemotherapy-Treated Breast Cancer Patients Undergoing Radiotherapy

NCT ID: NCT01740323

Last Updated: 2019-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2018-07-27

Brief Summary

The main purpose of the investigation is to determine if curcumin reduces NF-kB DNA binding and ultimately its downstream mediator IL-6 in patients receiving XRT for their breast cancer after having completed chemotherapy. Patients who have received prior chemotherapy will be eligible, because we have found that this enriched population is at particular risk for exhibiting increased NF-kB DNA binding and IL-6 following XRT.

Detailed Description

As many as 60% of breast cancer (BrCA) patients receiving radiation are known to develop fatigue with about 30% suffering persistent fatigue several months to years after treatment completion (12-23). The physical, psychological, and molecular mechanisms by which patients develop fatigue are poorly understood and most likely multi-factorial. One pathway that has received considerable attention is nuclear factor-kappa B (NF-kB)(24). The NF-kB pathway has emerged as having an important role not only in cancer treatment resistance but in the development of fatigue. NF-kB activation leads to over expression of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha, all factors related to inflammation and factors that have been found to be upregulated in patients receiving radiation as well as BrCA survivors with fatigue (25-29). A recently published study looking at TNF-alpha, fatigue and cachexia in cancer patients receiving docetaxol showed that NF-kB is upregulated in fatigued patients and that agents which inhibit TNF-alpha lead to better tolerance of chemotherapy dose escalation (30). Work by our group and others has shown that ionizing radiation increases NF-kB pathway activity in circulating immune cells (as well as within breast cancer cells) and that this effect is most pronounced in women previously treated with chemotherapy (31, 32). Our work has shown that the NF-kB pathway activity in circulating immune cells is also related to fatigue development in BrCA patients treated with radiation and that patients most at risk for persistent fatigue and NF-kB pathway activity are those who have received chemotherapy for their breast cancer (31).

Curcumin, a known inhibitor of NF-kB, has been shown to decrease NF-kB activation in human participants. In a recent study, 8 grams of curcumin by mouth daily for 8 weeks was well tolerated in patients with pancreatic cancer and other pre-malignant conditions with no associated toxicities (6, 8). Although there is concern over the body's absorption of curcumin, the bioavailability of curcumin in the study of pancreatic cancer patients was shown, with peak drug levels at 22 to 41ng/mL that remained relatively constant over the first 4 weeks of treatment with 8 grams of curcumin daily (8). Clinical trials with daily dosages of 1,125 to 2,500mg have also confirmed the safety of curcumin and also shown its ability to decrease inflammation in patients with rheumatoid arthritis and in post-operative patients (6, 33, 34). In vivo murine models of chronic fatigue syndrome have also shown that curcumin may also alleviate symptoms of fatigue (35). While these studies are promising, very little is known about the capacity of Meriva to inhibit NF-kB in women treated for BrCA. We hypothesize that oral Meriva, a known inhibitor of NF-kB, may be used to decrease levels of NF-kB activity in BrCA patients previously treated with chemotherapy who go on to receive radiotherapy (XRT), a carefully chosen group of patients at particular risk for high levels of NF-kB DNA binding (a direct measure of NF-kB pathway activity).

We have chosen to administer oral Meriva, 500mg BID, in our patient population based on the above data. Meriva-500 is a curcumin formulation that also contains phosphatidylcholine, derived from soy that has been shown to aid in absorption of curcumin (9), permitting a lower overall dose of curcumin. Of note, 1000 mg Meriva contains 200 mg curcuminoids (>90% curcumin).

By decreasing activity of NF-kB and ultimately plasma IL-6, fatigue may improve in BrCA patients taking Meriva. Results from this study will contribute to the limited research available on the capacity of curcumin treatment, including Meriva, to inhibit NF-kB activation in vivo as well as symptoms of fatigue associated with excessive NF-kB pathway activity in BRCA patients.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

daily placebo for 6 weeks

Curcumin

500 mg BID

Group Type: EXPERIMENTAL

Curcumin

Intervention Type: DRUG

500 mg BID

Interventions

Placebo

daily placebo for 6 weeks

Intervention Type: DRUG

Curcumin

500 mg BID

Intervention Type: DRUG

Other Intervention Names

Meriva

Eligibility Criteria

Inclusion Criteria

• Female breast cancer patients over the age of 18 will be recruited for this study. Patients enrolled in the study will meet standard criteria for whole breast XRT.

Exclusion Criteria

• Subjects will be excluded for a number of medical conditions that are contraindications to XRT and/or might confound the relationship among fatigue, and inflammation, including pregnancy, major psychiatric disorders, autoimmune or inflammatory disorders, chronic infectious diseases (e.g. HIV, hepatitis B or C), neurologic disorders and uncontrolled cardiovascular, metabolic, pulmonary or renal disease (as determined by medical history, physical examination and laboratory testing). Subjects with a history of a major psychiatric disorder including Schizophrenia or Bipolar Disorder or a diagnosis of Substance Abuse or Dependence within the past 1 year (as determined by standardized psychiatric interview) will be excluded. Subjects taking drugs known to affect the immune system (e.g. glucocorticoids, methotrexate) will also be excluded. Subjects using supplements or other natural products with one week of starting medications, excluding vitamins and calcium supplementation or at the discretion of the attending physician, will be excluded. Patients who have evidence of infection as determined by history, physical exam or laboratory testing (complete blood count and urinalysis) at baseline will be excluded. In addition, patients who develop evidence of infection (as determined by history, physical exam or laboratory testing) during the study will be discontinued from the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Andrew H Miller

OTHER

Sponsor Role: lead

Responsible Party

Andrew H Miller

Sponsor Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Andrew H Miller, MD

Role: PRINCIPAL_INVESTIGATOR

Emory Winship Cancer Institute

Locations

Emory University

Atlanta, Georgia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Winship2139-11

Identifier Type: OTHER

Identifier Source: secondary_id

R21CA178603

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00055328

Identifier Type: -

Identifier Source: org_study_id