Clinical trial NCT01823562: Aborption and Metabolism of Lyophilized Black Raspberry Food Products in Men With Prostate Cancer Undergoing Surgery
Official title: Dietary Fruit Bioactives and Prostate Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Stage I Prostate Cancer
Stage IIA Prostate Cancer
Stage IIB Prostate Cancer
Stage III Prostate Cancer
Keywords: Lyophilized Black Raspberry
Prostate Cancer
Surgery
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2013-04-04
Enrollment: 56
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Adverse events assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
timeFrame: Up to 30 days after completion of study treatment
measure: Compliance determined by consumption of at least 80% of black raspberries (BRB) and positive tests for urinary berry metabolites
timeFrame: Up to 6 weeks
Secondary outcomes:
measure: Presence of black raspberry metabolites in the urine collected 24 hours before surgery
timeFrame: Up to 6 weeks
measure: Changes in PSA or PSA doubling time
timeFrame: Up to 6 weeks
measure: Black Raspberry metabolites levels in the prostate tissue removed at surgery
timeFrame: Up to 6 weeks
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Steven Clinton
role: PRINCIPAL_INVESTIGATOR
References: