Stage IIA Prostate Cancer, Stage IIB Prostate Cancer, Stage III Prostate Cancer, Stage I Prostate Cancer
Conditions
Keywords
Lyophilized Black Raspberry, Prostate Cancer, Polyphenols
Brief summary
This Phase I/Ib trial is studying the absorption and metabolism of phytochemicals found in black raspberries in men undergoing surgery for prostate cancer. This knowledge will help us design future chemoprevention studies and assist in making future dietary recommendations for men at high risk for prostate cancer.
Detailed description
PRIMARY OBJECTIVES: I. To conduct a dose-escalation study to determine safety and compliance of varying lyophilized black raspberry (LBR) delivery vehicles (a confection and a nectar) at two different doses. SECONDARY OBJECTIVES: I. To precisely quantify changes in the content and distribution of black raspberry phytochemicals and their metabolites in the blood and urine and correlate these concentrations with prostate tissue phytochemicals. II. Measure the ability of black raspberry gummy confection and nectar in altering hormonal patterns (lower insulin-like growth factor-1 \[IGF-I\], higher insulin-like growth factor-binding protein 3 \[IGF-BP3\], lower androgens) consistent with reduced prostate carcinogenesis and in parallel with an enhanced capacity to quench reactive oxygen. III. Investigate histopathologic, immunologic, and molecular biomarkers associated with prostate carcinogenesis that may serve as surrogate endpoint biomarkers and provide information regarding their ability to be modulated by black raspberries. IV. Determine if consumption of black raspberries alters molecular markers in the human prostate including: (a) neuroendocrine markers such as IGF-I and IGF-BP3, (b) signal transduction markers such as phosphatase and tensin homologue (PTEN) and phospho-AKT, and (c) angiogenesis regulators such as (vascular epithelial growth factor (VEGF). V. Collect and store plasma and peripheral blood mononuclear cells (PBMCs) from each patient to assess systemic markers of inflammation and immune response. OUTLINE: This is a dose-escalation study of lyophilized black raspberry gummy confection and nectar. Patients are assigned to 1 of 7 treatment arms. ARM I: Patients follow a regular diet for 4-6 weeks and then undergo prostatectomy. ARM II: Patients follow a low polyphenol diet for 4-6 weeks and then undergo prostatectomy. ARM III: Patients follow a low ellagitannin diet for 4-6 weeks and then undergo prostatectomy. ARM IV: Patients follow a low ellagitannin diet and consume a lower-dose black raspberry confection daily for 4-6 weeks and then undergo prostatectomy. ARM V: Patients follow a low ellagitannin diet and consume a higher-dose black raspberry confection daily for 4-6 weeks and then undergo prostatectomy. ARM VI: Patients follow a low ellagitannin diet and consume a lower-dose black raspberry nectar daily for 4-6 weeks and then undergo prostatectomy. ARM VII: Patients follow a low ellagitannin diet and consume a higher-dose black raspberry nectar daily for 4-6 weeks and then undergo prostatectomy.
Interventions
OTHERquestionnaire administration
Ancillary studies
DRUGlyophilized black raspberry confection
Given PO
OTHERlaboratory biomarker analysis
Correlative studies
DIETARY_SUPPLEMENTdietary intervention
Follow a low polyphenol diet
PROCEDUREquality-of-life assessment
Ancillary studies
Sponsors
Ohio State University Comprehensive Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
* Have biopsy proven carcinoma of the prostate * Have chosen a radical prostatectomy for treatment of their disease after the medical team has presented all possible treatment options * Not be receiving neoadjuvant hormonal or chemotherapy (other clinical trials) * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Not currently taking berry dietary supplements, or "alternative" products (Acai berry, pomegranate, black raspberry, Optiberry, Juice Plus) * Have BUN/Cr (blood urea nitrogen and serum creatinine) within normal limits * Have liver enzymes within normal limits * Have complete blood count (CBC) within normal limits * Have prothrombin time/partial thromboplastin time (PT/PTT/INR) within normal limits * Voluntarily agree to participate and sign an informed consent document * Agree to have prostate biopsy blocks provided to the study for evaluation * Agree to consume a standardized vitamin and mineral supplement and avoid other nutrition, dietary, or alternative medications/supplements for the duration of the study * Agree to follow a controlled polyphenolic and/ or ellagitannin diet
Exclusion criteria
* Have an active malignancy other than prostate cancer that requires therapy * Have a prostate biopsy with less than 5% cancer involvement * Have a history of traumatic or surgical castration * Have a history of pituitary hormone diseases that currently require supplemental hormonal administration (thyroid hormones, adrenocorticotropic hormone \[ACTH\], growth hormone) or other endocrine disorders requiring hormone administration with the exception of diabetes and osteoporosis * Are taking certain medications; no concurrent finasteride (Proscar) or other hormonal agents for chemoprevention/treatment of benign prostate hyperplasia (BPH); utilizing prescription medications for urinary outlet obstructive symptoms will not be permitted; the use of non-prescription substances to improve urinary tract symptoms will not be permitted (i.e. Saw Palmetto, other herbal, alternative products) * Have a known allergy to black raspberries, corn, and wheat products or those who have never consumed any of these products * Have active metabolic or digestive illnesses such as malabsorptive disorders (Crohn's, Celiac disease, irritable bowel syndrome \[IBS\]), renal insufficiency, hepatic insufficiency, cachexia, or short bowel syndrome * Have significant loss of gastrointestinal organs due to surgery, except for appendix * Have altered immunity such as autoimmune disorders, cancer, anemia, hemophilia, and blood dyscrasias * Have noticeable open lesions in the oral cavity, sores that have not healed for more than 2 months or have a history of leukoplakia, tumors of the buccal cavity, throat, and lips * Have difficulty swallowing (dysphagia), pain with swallowing (odynophagia), salivary gland dysfunction, or xerostomia (dry mouth) * Are taking medications that inhibit clotting (warfarin sodium) or using prescribed oral rinses (Peridex)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events Assessed Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Up to 30 days after completion of study treatment | Adverse events were measured by asking participants at each study visit about any new symptoms which may or may not be related to the intervention. No adverse events were reported from any subjects. |
| Percentage of Intervention Consumed | Up to 6-weeks | A cohort will be considered compliant if the group mean consumption of the intervention product is at least 80%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of Black Raspberry Metabolites in the Urine Collected 24 Hours Before Surgery | 24 hours | At the baseline enrollment, subjects provided a spot urine sample. One day prior to surgery, subjects collected a 24-h urine sample. Spot urine samples were used to estimate individual ET exposure at baseline, but not specifically for comparison to 24-h urine sample collection at the close of the intervention. UPLC eluate was introduced to a triple quadrupole mass spectrometer (QuattroUltima,Waters Corp., Beverley,MA) via an electrospray mode operated in positive ion mode without splitting flow. Standards of urolithin A, B, C, D, methyl A, and dimethyl A were used for external calibration. Baseline urine analysis was determined from a spot urine collection and metabolite profiles were normalized to urinary creatinine levels. Final urinary analysis was based on a 24-h urine collection and metabolite profiles were normalized to 24-h urine volumes. |
| Changes in PSA or PSA Doubling Time | Up to 6 weeks | Analyzed on the log scale using a repeated measures linear model to judge the effect of treatment group in terms of fold-differences from baseline while controlling for BMI and age. Confidence intervals for dichotomous variables will be made using exact methods and confidence intervals for rank correlations between quantitative variables will be made using Fisher's transformation. |
| Black Raspberry Metabolites Levels in the Prostate Tissue Removed at Surgery | Up to 6 weeks | Confidence intervals for dichotomous variables will be made using exact methods and confidence intervals for rank correlations between quantitative variables will be made using Fisher's transformation. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSteven Clinton
Ohio State University Comprehensive Cancer Center
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62 years STANDARD_DEVIATION 3 |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
None listed