Prostate Cancer
Conditions
Brief summary
This study will examine the utility of chitosan for reduction of blood or tissue levels of AGEs in patients with prostate cancer who are clinically stable on androgen-deprivation therapy.
Detailed description
The overall goal of this study is to identify a safe dose of the metabolic supplement, Chitosan that can help reduce AGE (advanced glycation endproducts) levels in patients with prostate cancer. Chitosan is a naturally occurring substance found in shellfish. This study will be using Chitosan prepared from the shells of cold-water shrimp. Chitosan is approved by the FDA for use in wound dressings and has been used in published clinical trials for weight loss but is not approved for the purposes of this study. AGEs are a type of metabolite, or substance, found in food and produced in the body. The researchers helping conduct this study have found a potential link between AGE levels and cancer. Participation in this study will require three study visits over the course of about 3 months. During these visits subjects will be asked to provide blood and stool samples as well as complete surveys about their quality of life.
Interventions
DRUGChitosan
Increasing dose levels from 500mg twice daily to 2000mg twice daily for up to 85 days.
Sponsors
Medical University of South Carolina
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion: 1. Confirmation of adenocarcinoma of the prostate that is documented by one of the following: pathology report or clinic note with documented history of prostate cancer. 2. Subjects must be receiving ADT with a GnRH agonist or antagonist, with or without an anti-androgen or testosterone synthesis inhibitor. The current testosterone level must be documented to be \<50ng/dL at enrollment. Subjects whose ADT is interrupted may enroll or continue on study as long as the testosterone is documented to remain \<50ng/dL for the entire duration of study participation. Subjects who have undergone orchiectomy are also eligible. 3. Subjects must have adequate hematologic, renal, and hepatic function at baseline, as follows: * Hematology parameters: ANC \>1000/mcL, platelets \> 100,000/mcL, Hgb \>8.0gm/dL * Renal Function: eGFR of ≥ 45mls/min using Cockgroft and Gault formula * Liver Function: Total bilirubin ≤ULN, AST and ALT \<1.5x ULN 4. Able to swallow and retain oral medication 5. ECOG performance status of 0 - 2 6. Ability to sign written informed consent 7. Testosterone level \<50ng/dL at time of enrollment. 8. Age 18 or older. 9. May have had prior radiation therapy, surgery, or cryoablation for primary prostate cancer 10. May have had prior cytotoxic chemotherapy for metastatic prostate cancer, prior treatment with genomically-targeted agents, or Provenge Exclusion: 1. Known allergy to chitosan or shellfish. 2. History of receiving more than 2 classes of ADT. 3. Chronic constipation (BM \< 3x weekly), history of malabsorption or history of daily laxative use. 4. Patients requiring medication administration with lunch or dinner or at a frequency of three or more times per day are not eligible. 5. Current use of chitosan, sevelamer, and/or glucosamine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose as Assessed by Number of Participants Who Experienced a Dose Limiting Toxicity | 112 days | The maximum tolerated dose is defined as the dose that produces no more than 1 dose-limiting toxicity (DLT)in 6 subjects. Per protocol a DLT is defined as Grade 3 or higher hypophosphatemia and/ or Grade 3 or higher of any of the following toxicities, that the investigator deems related to chitosan, that do not improve or resolve within 7 days of onset: flatulence, increased stool bulkiness, bloating, nausea, heartburn |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Inflammation (Plasma Cytokines, Toll-like Receptor Signaling) | 112 days | No participants were analyzed for this outcome, therefore no data was collected. Study was terminated. |
| Change in Insulin Resistance (HOMA-IR) | 112 days | No participants were analyzed for this outcome, therefore no data was collected. Study was terminated. |
| Changes in Bowel Permeability (Plasma Endotoxin) | 112 days | No participants were analyzed for this outcome, therefore no data was collected. Study was terminated. |
| Change in Redox Status (RedoxSys, Serum Oxidized Glutathione) | 112 days | No participants were analyzed for this outcome, therefore no data was collected. Study was terminated. |
| Correlate Changes in Serum AGE Levels (Pan-AGE, Carboxymethyllysine, Methylglyoxal | 112 days | No participants were analyzed for this outcome, therefore no data was collected. Study was terminated. |
| Measure the Frequency of a > 30% Reduction in Total AGE Levels From the Pretreatment Level. | 112 days | No participants were analyzed for this outcome, therefore no data was collected. Study was terminated. |
| Changes in Microbiome Diversity (16s rDNA Sequencing) | 112 days | No participants were analyzed for this outcome, therefore no data was collected. Study was terminated. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chitosan Dose Level 1 ChChitosan dosing 500mg orally twice daily for 85 days. | 3 |
| Chitosan Dose Level 2 Chitosan dosing 1000mg orally twice daily for 85 days. | 3 |
| Chitosan Dose Level 3 Chitosan dosing 1500mg orally twice daily for 85 days. | 3 |
| Chitosan Dose Level 4 Chitosan dosing 2000mg orally twice daily for 85 days. | 3 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Chitosan Dose Level 2 | Chitosan Dose Level 3 | Chitosan Dose Level 4 | Chitosan Dose Level 1 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 11 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Continuous | 75 years | 73 years | 69 years | 68 years | 69.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 11 Participants |
| Region of Enrollment United States | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 12 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 2 / 3 | 3 / 3 | 2 / 3 | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 | 1 / 3 |
Outcome results
Primary
Maximum Tolerated Dose as Assessed by Number of Participants Who Experienced a Dose Limiting Toxicity
The maximum tolerated dose is defined as the dose that produces no more than 1 dose-limiting toxicity (DLT)in 6 subjects. Per protocol a DLT is defined as Grade 3 or higher hypophosphatemia and/ or Grade 3 or higher of any of the following toxicities, that the investigator deems related to chitosan, that do not improve or resolve within 7 days of onset: flatulence, increased stool bulkiness, bloating, nausea, heartburn
Time frame: 112 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Level 1 | Maximum Tolerated Dose as Assessed by Number of Participants Who Experienced a Dose Limiting Toxicity | 0 Participants |
| Dose Level 2 | Maximum Tolerated Dose as Assessed by Number of Participants Who Experienced a Dose Limiting Toxicity | 0 Participants |
| Dose Level 3 | Maximum Tolerated Dose as Assessed by Number of Participants Who Experienced a Dose Limiting Toxicity | 0 Participants |
| Dose Level 4 | Maximum Tolerated Dose as Assessed by Number of Participants Who Experienced a Dose Limiting Toxicity | 0 Participants |
Secondary
Change in Inflammation (Plasma Cytokines, Toll-like Receptor Signaling)
No participants were analyzed for this outcome, therefore no data was collected. Study was terminated.
Time frame: 112 days
Population: No participants were analyzed for this outcome, therefore no data was collected. Study was terminated.
Secondary
Change in Insulin Resistance (HOMA-IR)
No participants were analyzed for this outcome, therefore no data was collected. Study was terminated.
Time frame: 112 days
Population: No participants were analyzed for this outcome, therefore no data was collected. Study was terminated.
Secondary
Change in Redox Status (RedoxSys, Serum Oxidized Glutathione)
No participants were analyzed for this outcome, therefore no data was collected. Study was terminated.
Time frame: 112 days
Population: No participants were analyzed for this outcome, therefore no data was collected. Study was terminated.
Secondary
Changes in Bowel Permeability (Plasma Endotoxin)
No participants were analyzed for this outcome, therefore no data was collected. Study was terminated.
Time frame: 112 days
Population: No participants were analyzed for this outcome, therefore no data was collected. Study was terminated.
Secondary
Changes in Microbiome Diversity (16s rDNA Sequencing)
No participants were analyzed for this outcome, therefore no data was collected. Study was terminated.
Time frame: 112 days
Population: No participants were analyzed for this outcome, therefore no data was collected. Study was terminated.
Secondary
Correlate Changes in Serum AGE Levels (Pan-AGE, Carboxymethyllysine, Methylglyoxal
No participants were analyzed for this outcome, therefore no data was collected. Study was terminated.
Time frame: 112 days
Population: No participants were analyzed for this outcome, therefore no data was collected. Study was terminated.
Secondary
Measure the Frequency of a > 30% Reduction in Total AGE Levels From the Pretreatment Level.
No participants were analyzed for this outcome, therefore no data was collected. Study was terminated.
Time frame: 112 days
Population: No participants were analyzed for this outcome, therefore no data was collected. Study was terminated.