Aborption and Metabolism of Lyophilized Black Raspberry Food Products in Men With Prostate Cancer Undergoing Surgery

Study Overview
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Brief Summary
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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
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PRIMARY OBJECTIVES: I. To conduct a dose-escalation study to determine safety and compliance of varying lyophilized black raspberry (LBR) delivery vehicles (a gummy 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 receive lower-dose black raspberry gummy orally (PO) daily for 4-6 weeks and then undergo prostatectomy. ARM V: Patients follow a low ellagitannin diet and receive higher-dose black raspberry gummy PO daily for 4-6 weeks and then undergo prostatectomy. ARM VI: Patients follow a low ellagitannin diet and receive lower-dose black raspberry nectar PO daily for 4-6 weeks and then undergo prostatectomy. ARM VII: Patients follow a low ellagitannin diet and receive higher-dose black raspberry nectar PO daily for 4-6 weeks and then undergo prostatectomy.

Official Title
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Dietary Fruit Bioactives and Prostate Cancer

Conditions
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Stage I Prostate Cancer, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer, Stage III Prostate Cancer

Intervention / Treatment
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* Drug: lyophilized black raspberry confection
* Other: laboratory biomarker analysis
* Dietary Supplement: dietary intervention
* Dietary Supplement: dietary intervention
* Procedure: quality-of-life assessment
* Other: questionnaire administration


Participation Criteria
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Eligibility Criteria
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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)
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I (regular diet)<br>Patients follow a regular diet for 4-6 weeks and then undergo prostatectomy. | Other: laboratory biomarker analysis<br>* Correlative studies<br>Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;Other: questionnaire administration<br>* Ancillary studies<br>|
| Active Comparator: Arm II (low polyphenol diet)<br>Patients follow a low polyphenol diet for 4-6 weeks and then undergo prostatectomy. | Other: laboratory biomarker analysis<br>* Correlative studies<br>Dietary Supplement: dietary intervention<br>* Follow a low polyphenol diet<br>* Other names: intervention, dietary;Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;Other: questionnaire administration<br>* Ancillary studies<br>|
| Active Comparator: Arm III (low ellagitannin diet)<br>Patients follow a low ellagitannin diet for 4-6 weeks and then undergo prostatectomy. | Other: laboratory biomarker analysis<br>* Correlative studies<br>Dietary Supplement: dietary intervention<br>* Follow a low ellagitannin diet<br>* Other names: intervention, dietary;Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;Other: questionnaire administration<br>* Ancillary studies<br>|
| Experimental: Arm IV (lower-dose lyophilized black raspberry gummy)<br>Patients follow a low ellagitannin diet and receive lower-dose black raspberry gummy PO daily for 4-6 weeks and then undergo prostatectomy. | Drug: lyophilized black raspberry confection<br>* Given PO<br>* Other names: LBR confection;Other: laboratory biomarker analysis<br>* Correlative studies<br>Dietary Supplement: dietary intervention<br>* Follow a low ellagitannin diet<br>* Other names: intervention, dietary;Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;Other: questionnaire administration<br>* Ancillary studies<br>|
| Experimental: Arm V (higher-dose black raspberry gummy)<br>Patients follow a low ellagitannin diet and receive higher-dose black raspberry gummy PO daily for 4-6 weeks and then undergo prostatectomy. | Drug: lyophilized black raspberry confection<br>* Given PO<br>* Other names: LBR confection;Other: laboratory biomarker analysis<br>* Correlative studies<br>Dietary Supplement: dietary intervention<br>* Follow a low ellagitannin diet<br>* Other names: intervention, dietary;Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;Other: questionnaire administration<br>* Ancillary studies<br>|
| Experimental: Arm VI (lower-dose black raspberry confection)<br>Patients follow a low ellagitannin diet and receive lower-dose black raspberry confection PO daily for 4-6 weeks and then undergo prostatectomy. | Drug: lyophilized black raspberry confection<br>* Given PO<br>* Other names: LBR confection;Other: laboratory biomarker analysis<br>* Correlative studies<br>Dietary Supplement: dietary intervention<br>* Follow a low ellagitannin diet<br>* Other names: intervention, dietary;Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;Other: questionnaire administration<br>* Ancillary studies<br>|
| Experimental: Arm VII (higher-dose black raspberry confection)<br>Patients follow a low ellagitannin diet and receive higher-dose black raspberry confection PO daily for 4-6 weeks and then undergo prostatectomy. | Drug: lyophilized black raspberry confection<br>* Given PO<br>* Other names: LBR confection;Other: laboratory biomarker analysis<br>* Correlative studies<br>Dietary Supplement: dietary intervention<br>* Follow a low ellagitannin diet<br>* Other names: intervention, dietary;Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;Other: questionnaire administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Compliance determined by consumption of at least 80% of black raspberries (BRB) and positive tests for urinary berry metabolites | A cohort will be considered compliant if the group mean consumption of the intervention product is at least 80%. | Up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence of black raspberry metabolites in the urine collected 24 hours before surgery | 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 body mass index (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. | Up to 6 weeks | 
| Changes in PSA or PSA doubling time | 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. | Up to 6 weeks | 
| Black Raspberry metabolites levels in the prostate tissue removed at surgery | 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. | Up to 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lyophilized Black Raspberry, Prostate Cancer, Surgery