Phase II A Trial of Curcumin Among Patients With Prevalen... | NCT00365209

ID	Type	Description	Link
NCI-2013-00449	Registry Identifier	CTRP (Clinical Trial Reporting Program)
UIC-2005-0617
CDR0000483003
UCIRVINE-2005-4586
UIC HS# 2005-0617
CCUM-HUM00000731
P30CA062203	U.S. NIH Grant/Contract		View source
2005-0617	Other Identifier	Chao Family Comprehensive Cancer Center
UCI04-2-01	Other Identifier	DCP
N01CN35160	U.S. NIH Grant/Contract		View source

Description Module

Detailed Description

PRIMARY OBJECTIVES:

I. To determine mean percentage change from baseline in prostaglandin E2 (PGE2) within ACF pre and post 30 days of curcumin administration at a specified dose.

SECONDARY OBJECTIVS:

I. To determine mean percentage change from baseline in 5-hydroxy-eicosatetraenoic acid (5-HETE) within ACF pre and post 30 days of curcumin administration at a specified dose.

II. To determine mean percentage change from baseline in PGE2 and 5-HETE within comparison normal mucosa pre and post 30 days of curcumin administration at a specified dose.

III. To quantify corresponding enzyme changes in the cyclooxygenases (COX-1, COX-2,) and lipoxygenase (5-LOX) protein abundance. Semi-quantitative changes in these proteins will be measured by western blotting and correlated with changes in prostaglandins and leukotrienes respectively.

IV. Document changes in total ACF number. V. Determine proliferation by Ki-67 IHC in rectal mucosa pre and post therapy and correlate with changes in ACF number and size.

VI. Determine curcumin concentration in rectal mucosa after 30 days therapy and correlate with PGE2 and 5-HETE changes described above.

VII. Measure glutathione peroxidase (GPx) activity within the colon pre and post therapy as an indirect marker of reduced oxidative stress within the colonic epithelium.

VIII. Ensure safety of all participants during course of study investigation. IX. Determine the curcumin concentration in plasma before and after treatment.

OUTLINE: This is a multicenter, nonrandomized, uncontrolled study.

Patients receive 1 of 2 doses of oral curcumin once daily. Treatment continues for 30 days in the absence of unacceptable toxicity or disease progression.

Blood and tissue biopsies are obtained by sigmoidoscopy or colonoscopy at baseline and at day 30 for correlative biomarker studies. The change in prostaglandin E_2 (PGE_2) is assessed by enzyme immunoassay, 5-hydroxy-eicosatetraenoic acid (5-HETE) by high-performance liquid chromatography, cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX) by western blotting, Ki-67 by immunohistochemistry, and glutathione peroxidase (GPx) by spectrophotometric assay.

After completion of study therapy, patients are followed at 1 week.

PROJECTED ACCRUAL: A total of 48 patients will be accrued for this study.

Label	Type	Description	Intervention Names
2g (curcumin)	Experimental	Patients receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression.	Other: laboratory biomarker analysis Other: pharmacological study Drug: curcumin
4g (curcumin)	Experimental	Patients receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression.	Other: laboratory biomarker analysis Other: pharmacological study Drug: curcumin

Name	Type	Description	Arm Group Labels	Other Names
laboratory biomarker analysis	Other	Correlative studies	2g (curcumin) 4g (curcumin)

Measure	Description	Time Frame
Baseline in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF)	Baseline prostaglandin E2 (PGE2) values found in rectal aberrant crypt foci (ACF) tissue	Baseline
Post-treatment in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF)	Post-treatment prostaglandin E2 (PGE2) values found in rectal aberrant crypt foci (ACF) tissue	At 30 day

Measure	Description	Time Frame
Baseline in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Within Aberrant Crypt Foci (ACF)	Baseline 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in rectal aberrant crypt foci (ACF) tissue	Baseline
Post-treatment in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Within Aberrant Crypt Foci (ACF)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Current smoker with > 3 pack-year total smoking history
Subjects taking NSAIDS or ASA < 10 days month are eligible but must undergo 14 day washout and refrain from use during the study
Subjects who are:
- Having a clinically indicated screening/surveillance colonoscopy (e.g. due to risk factors, personal history, or symptoms) OR
- Not having a colonoscopy but are otherwise eligible. These subjects would undergo a flexible sigmoidoscopy.
ECOG performance status 0-2 (Karnofsky > 60%)
No severe organ dysfunction which might increase bleeding risk:
- Demonstrated by: Normal hematologic status (WBC > 3,000/mm^3, hemoglobin > 10.0 gm/dl, and platelet-count >100,000/mm^3), normal hepatic function (bilirubin < 1.5 mg/dl, transaminases < 1.5x institutional norms), and normal renal function (serum creatinine < 2.0 mg/dl, documented in clinical chart 28 days prior to enrollment
Healthy current smokers (1 cigarette in previous yr) with > 3-pack year of cigarette smoking and able to provide written informed consent; there are no gender restrictions
The effects of curcumin on the developing human fetus at the recommended therapeutic dose are unknown; for this reason women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

NSAID or ASA use > 10 days /month; any current glucocorticoid use or omega 3-fatty acid supplement use
Evidence of the following chronic medical conditions such as:
- Pregnant or lactating women and/or women who are contemplating pregnancy during the duration of the protocol
- History of chronic inflammatory bowel disease or prior pelvic irradiation
- History of peptic ulcer disease (PUD) endoscopically confirmed < 5 yrs from enrollment date
- Newly diagnosed colorectal cancer or advanced adenoma < 1 yr from enrollment
- Unspecified history of bleeding or coagulation disorder reported by patient or in medical history
- Hereditary Colon Cancer syndromes (FAP or HNPCC)
Participants may not be receiving any other investigational agents
History of contact dermatitis from turmeric
Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant women are excluded from this study because curcumin is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with curcumin, breastfeeding should be discontinued if the mother is treated with curcumin

Name	Affiliation	Role
Frank Meyskens	Chao Family Comprehensive Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Chao Family Comprehensive Cancer Center		Orange	California	92868	United States

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Curcumin	Stage 1: Particpants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Particpants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

ID	Title	Description
BG000	Curcumin	Stage 1: Patients receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Patients receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	BG00043

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Baseline in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF)

Baseline prostaglandin E2 (PGE2) values found in rectal aberrant crypt foci (ACF) tissue

The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 21 participants) and Stage2 4 g curcumin: (N = 19 participants)

Posted

Mean

Standard Deviation

µg/g protein

Baseline

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG00040

Title

Denominators

Categories

Stage1 2 g (curcumin) N=21

Title	Measurements
	OG0001.1± 1.8

Stage2 4 g (curcumin) N=19

Title	Measurements
	OG0003.4± 4.8

Secondary

Baseline in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Within Aberrant Crypt Foci (ACF)

Baseline 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in rectal aberrant crypt foci (ACF) tissue

The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 21 participants), Stage2 4 g curcumin: (N = 19 participants)

Posted

Mean

Standard Deviation

µg/g protein

Baseline

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG000

Secondary

Post-treatment in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Within Aberrant Crypt Foci (ACF)

Post-treatment 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in rectal aberrant crypt foci (ACF) tissue

The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 21 participants), Stage2 4 g curcumin: (N = 19 participants)

Posted

Mean

Standard Deviation

µg/g protein

At 30 Day

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG000

Secondary

Baseline in Prostaglandin E2 (PGE2) Level in Normal Mucosa

Baseline prostaglandin E2 (PGE2) values found in normal mucosa rectal tissue

The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 21 participants), Stage2 4 g curcumin: (N = 19 participants)

Posted

Mean

Standard Deviation

µg/g protein

Baseline

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG000

Secondary

Post-treatment in Prostaglandin E2 (PGE2) Level in Normal Mucosa

Post-treatment prostaglandin E2 (PGE2) values found in normal mucosa rectal tissue

The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 21 participants), Stage2 4 g curcumin: (N = 19 participants)

Posted

Mean

Standard Deviation

µg/g protein

At 30 day

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG000

Secondary

Baseline in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Level in Normal Mucosa

Baseline 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in normal mucosa rectal tissue

The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 21 participants), Stage2 4 g curcumin: (N = 19 participants)

Posted

Mean

Standard Deviation

µg/g protein

Baseline

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG000

Secondary

Post-treatment in 5-hydroxy-eicosatetraenoic Acid (5-HETE) Level in Normal Mucosa

Post-treatment 5-hydroxy-eicosatetraenoic acid (5-HETE) values found in normal mucosa rectal tissue

The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 21 participants), Stage2 4 g curcumin: (N = 19 participants)

Posted

Mean

Standard Deviation

µg/g protein

At 30 day

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG000

Secondary

Change in Cyclooxygenases (COX-1, COX-2), and Lipoxygenase (5-LOX) Protein Abundance

The protein levels for each enzyme will be expressed as an absolute change from baseline and graphed against % change of its enzyme product in the same individual. The degree of correlation between these parameters will be assessed by either Pearson's correlation coefficient or Spearman's rank order correlation coefficient.

There is not enough tissue for the analysis, so no data is provided.

Posted

Baseline to 30 days

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG000

Secondary

Changes in Total Aberrant Crypt Foci (ACF) Number

Changes in total aberrant crypt foci (ACF) number = Number of ACF at pre-treatment - Number of ACF at post-treatment

The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 22 participants), Stage2 4 g curcumin: (N = 19 participants)

Posted

Median

Full Range

Number of ACF

Baseline to 30 days

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG000

Secondary

Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Proximal Third

The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 22 participants), Stage2 4 g curcumin: (N = 17 participants)

Posted

Mean

Standard Deviation

percentage of labeled cells

Baseline

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG000

Primary

Post-treatment in Prostaglandin E2 (PGE2) Within Aberrant Crypt Foci (ACF)

Post-treatment prostaglandin E2 (PGE2) values found in rectal aberrant crypt foci (ACF) tissue

The analysis is based on participants whose data are evaluable and available. Stage1 2g curcumin: (N = 21 participants), Stage2 4 g curcumin: (N = 19 participants)

Posted

Mean

Standard Deviation

µg/g protein

At 30 day

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG000

Secondary

Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Proximal Third

The analysis is based on participants whose data are evaluable and available. Stage1 2 g crucumin: (N = 22 participants), Stage2 4 g curcumin: (N = 19 participants)

Posted

Mean

Standard Deviation

percentage of labeled cells

At 30 day

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG000

Secondary

Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Middle Third

The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 22 participants), Stage2 4 g curcumin : (N = 17 participants).

Posted

Mean

Standard Deviation

percentage of labeled cells

Baseline

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG000

Secondary

Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Middle Third

The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 22 participants), Stage2 4 g curcumin: (N = 19 participants)

Posted

Mean

Standard Deviation

percentage of labeled cells

At 30 day

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG000

Secondary

Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Distal Third

The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 22 participants), Stage2 4 g curcumin: (N = 17 participants)

Posted

Mean

Standard Deviation

percentage of labeled cells

Baseline

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG000

Secondary

Proliferation by Ki-67 Immunohistochemical Assay (IHC) in Normal Mucosa - Distal Third

The analysis is based on participants whose data are evaluable and available. Stage1 2 g curcumin: (N = 22 participants), Stage2 4 g curcumin: (N = 19 participants)

Posted

Mean

Standard Deviation

percentage of labeled cells

At 30 day

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG000

Secondary

Baseline Curcumin Concentration in Rectal Mucosa

If detectable in the rectal mucosa, it is predicted that curcumin concentrations and potentially curcumin conjugate concentrations will be associated with reduction in PGE2 and 5-HETE measured from colorectal mucosal biopsies. Pearson correlation coefficients between changes in baseline levels in these 2 parameters and curcumin concentration in rectal mucosa will be calculated. Endpoints may be log transformed as appropriate prior to analysis.

Samples from 21 participants in the 2g curcumin arm and 18 participants in the 4g curcumin arm were sent to be assayed. Detectable levels of curcumin in rectal mucosa were found in 1 participant in the 2g arm and none in participants on the 4g arm. Therefore, only 1 sample from the 2g arm and 0 samples from the 4g arm are reported here.

Posted

Mean

Standard Deviation

µg/g protein

Baseline

samples with detectable levels

Participants

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts

Secondary

Post-treatment Curcumin Concentration in Rectal Mucosa

The analysis is based on 39 participants (21 participants from 2g curcmin, and 18 participants from 4 g curcumin). In 2g group, a total of 5 samples with detectable levels were analyzed. In 4g group, a total of 3 samples with detectable levels were analyzed.

Posted

Mean

Standard Deviation

µg/g protein

At 30 day

samples with detectable levels

Participants

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants

Secondary

Baseline Curcumin Plasma Concentrations

Baseline curcumin conjugate concentrations will be measured directly from the subject's plasma and then the change in concentrations after the last dose of study drug will be measured. Concentrations will be measured and statistically evaluated by paired t-test or Wilcoxon matched-pairs signed-ranks test, as appropriate.

Samples from 19 participants in the 4g curcumin arm were assayed. Detectable levels of curcumin in plasma were found in 4 participants in the 4g arm; therefore, 4 samples are reported here. Samples from participants in the 2g curcumin arm were not collected due to a delayed decision resulting with protocol modification and resource restrictions.

Posted

Mean

Standard Deviation

µg/mL

Baseline

samples with detectable levels

Participants

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants

Secondary

Post-treatment Curcumin Plasma Concentrations

Samples from 19 participants in the 4g curcumin arm were assayed. Detectable levels of curcumin in plasma were found in 2 participants in the 4g arm; therefore, 2 samples are reported here. Samples from participants in the 2g curcumin arm were not collected due to a delayed decision resulting with protocol modification and resource restrictions.

Posted

Mean

Standard Deviation

µg/mL

At 30 day

samples with detectable levels

Participants

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants

Secondary

Baseline Curcumin Conjugates Concentration in Rectal Mucosa

Samples from 21 participants in the 2g curcumin arm and 19 participants in the 4g curcumin arm were sent to be assayed. Detectable levels of curcumin conjugates in rectal mucosa were found in 0 participants in the 2g arm and 1 participant on the 4g arm. Therefore, 0 samples from the 2g arm and 1 sample from the 4g arm are reported here.

Posted

Mean

Standard Deviation

µg/g protein

Baseline

samples with detectable levels

Participants

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units

Secondary

Post-treatment Curcumin Conjugates Concentration in Rectal Mucosa

The analysis is based on 39 participants (21 participants from 2g curcumin group and 18 participatns from 4g curcumin group). In 2g group, a total of 13 samples with detectable levels were analyzed. In 4g group, a total of 12 samples with detectable levels were analyzed.

Posted

Mean

Standard Deviation

µg/g protein

At 30 day

samples with detectable levels

Participants

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts

Secondary

Baseline Curcumin Conjugates Plasma Concentrations

Samples from 19 participants in the 4g curcumin arm were assayed. Detectable levels of curcumin in plasma were found in 19 participants in the 4g arm; therefore, 19 samples are reported here. Samples from participants in the 2g curcumin arm were not collected due to a delayed decision resulting with protocol modification and resource restrictions.

Posted

Mean

Standard Deviation

µg/mL

Baseline

samples with detectable levels

Participants

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants

Secondary

Post-treatment Curcumin Conjugates Plasma Concentrations

Post-treatment curcumin conjugate concentrations will be measured directly from the subject's plasma and then the change in concentrations after the last dose of study drug will be measured. Concentrations will be measured and statistically evaluated by paired t-test or Wilcoxon matched-pairs signed-ranks test, as appropriate.

Posted

Mean

Standard Deviation

µg/mL

At 30 day

samples with detectable levels

Participants

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants

Secondary

Number of Participants at Each Adverse Event Grade Level

These participants completed the study. The data is from the final dataset which was available in 2013 following the publication.

Posted

Number

participants

Baseline to 30 days

ID	Title	Description
OG000	Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
YELLOW, SOFTER POO	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
ABDOMINAL CRAMPING	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
ABDOMINAL DISCOMFORT	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
BEGINNING OF INFLUENZA	General disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
BURNING WHEN PEE	Renal and urinary disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
CALMED MY STOMACH	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
COLD/SINUSES	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
CONSTIPATION	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
CURBED APPETITE	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
DECREASED APPETITE	Metabolism and nutrition disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
DIARRHEA	Gastrointestinal disorders	Non-systematic Assessment	EG0002 events2 affected22 at risk EG0010 events0 affected21 at risk
ELEVATED CREATININE	Investigations	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
EYE VISION IS BLURRY	Eye disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
FULLNESS	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
GAS	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
HEADACHE	Nervous system disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
HEADACHE AT NIGHT	Nervous system disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
HELPED BOWEL MOVEMENTS, MORE FREQUENT, LOOSER	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
IMPROVED, EASIER BOWEL MOVEMENTS	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
IMPROVED, SOFTER STOOL	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
IMPROVED; CURCUMIN HELPED CONSTIPATION; BEFORE GOING EVERY 3-4 DAYS, NOW EVERY 2 DAYS	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
IMPROVED; CURCUMIN WAS BETTER FOR BOWEL MOVEMENT, SOFTER STOOL	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
IMPROVED; LESS ACHEY	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
IMPROVED; MORE FREQUENT BOWEL MOVEMENTS	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
IMPROVED; NO LONGER CONSTIPATED, CONSTIPATION BEGAN IN 2006; NOW MORE FREQUENT BOWEL MOVEMENTS	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
IMPROVED; NOT TOO MUCH GAS IN THE STOMACH	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
ITCHING	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
ITCHING ALL OVER	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
LEFT AND RIGHT LEG LOWER EDEMA	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
LITTLE BLOATED	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
LITTLE BURNING IN STOMACH	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
LITTLE GAS	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
LOSS OF APPETITE	Metabolism and nutrition disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
LOWER BACK PAIN	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
MILD HEART BURN	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
NAUSEA	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
NO MORE CONSTIPATION, PILL REALLY HELPED	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
PEEING A LOT	Renal and urinary disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
PEPPER TASTE	Nervous system disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
SIDE HURTS	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
SLOW URINATION	Renal and urinary disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
SORE THROAT	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
STIFFNESS IN NECK	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0000 events0 affected22 at risk EG0011 events1 affected21 at risk
STOMACH UPSET AND RELATED PAINS	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
STRAINED SORE CHEST MUSCLES	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
UNUSUAL DREAM STATE	Psychiatric disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
VOMITTED AFTER TAKING PILLS	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
WEIRD DREAMS	Psychiatric disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0010 events0 affected21 at risk
YELLOW STOOL	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected22 at risk EG0012 events2 affected21 at risk

ID	Term
D019966	Substance-Related Disorders
D064419	Chemically-Induced Disorders
D001523	Mental Disorders

ID	Term
D036381	Diarylheptanoids
D006536	Heptanes
D000473	Alkanes
D006839	Hydrocarbons, Acyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D002396	Catechols
D010636	Phenols
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Stage1 2 g Curcumin	Stage 1: Participants receive 2 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally			0	22	12	22
EG001	Stage2 4 g Curcumin	Stage 2: Participants receive 4 grams of oral curcumin once daily. Treatment continues for up to 30 days in the absence of unacceptable toxicity or disease progression. laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies curcumin: Given orally			1	21	11	21