Effects of Pomegranate Juice or Extract on Rising PSA Levels in Men Following Primary Therapy for Prostate Cancer

Primary Objective:

To compare the effects of daily consumption of pomegranate liquid extract, and placebo on end-of-treatment (52 weeks) prostate-specific antigen (PSA) doubling time in male subjects who have rising serum PSA levels after primary therapy for localized prostate cancer.

Secondary Objectives:

1. To determine the effect of the pomegranate treatments on the change in serum PSA doubling time from baseline to end-of-treatment.
2. To evaluate the effects of the pomegranate treatments on changes in the health-related quality of life (QOL)
3. To determine the time to tumor recurrence
4. To assess the tolerability and toxicity of the pomegranate treatments
5. To determine the effect of the pomegranate treatments on response rates for positive serum PSA doubling times and for declining post-treatment serum PSA levels (negative doubling times)

Some studies suggest that diets with certain plant-based sources (plant chemicals) may help to reduce the risk of diseases, such as cancer and heart disease.

Pomegranate liquid extract is identical to pomegranate juice, but has a higher concentration of ingredients that are known to prevent damage to cells.

The placebo used in this study is a juice made by the study sponsor that looks and tastes like pomegranate liquid extract, but it does not have active ingredients, such as plant chemicals.

Before beginning screening for this study, you will be checked to make sure you do not have any allergic reaction to pomegranate liquid extract. You will be asked to drink one 4-ounce (1/2 cup) sample of pomegranate juice, mixed with pomegranate liquid extract, and placebo. You will then be watched by the study staff for about 30 minutes. If any signs and symptoms of allergic reactions are seen, appropriate medical attention will be provided, and you will not be able to proceed to the screening for this study. If you do not experience any signs of symptoms of allergic reactions, you will proceed to the screening for this study.

Before you can start on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. You will have your complete medical history recorded. You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate), height, and weight. You will have a digital (insertion by a finger) rectal exam. You will be asked to complete a food-frequency questionnaire, which will ask about what types of fruits and vegetables you eat and how often you eat them. It will take about 20 minutes to complete. You will also have a quality-of-life (QOL) questionnaire that will ask about your health, activities that might be affected by your health, and/or about pain that you have recently had. It will take about 15 minutes to complete this questionnaire.

If you have diabetes and have not had your blood sugar levels tested in the past 3 months, you will have blood drawn (about 1 tablespoon) to check your HbA1c (which will show your blood sugar levels).

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1 of the 2 study groups (pomegranate liquid extract or placebo). Participants in one group will receive pomegranate liquid extract. Participants in the other group will receive placebo. There will be a 2 out of 3 chance that you will receive pomegranate liquid extract.

You will be notified by telephone call about 7 days after your screening visit that you are eligible to take part in the study. You will also be told the delivery date for your study juice and a study-product diary.

This is a double-blinded study, which means that neither you nor your doctor or any medical staff involved in your care, will know which product you receive until the study is complete. However, the study doctor can find out which product you are receiving (if there is an emergency or if it is necessary to know for your health).

The study drink will be shipped to M. D. Anderson and then shipped to you directly from M. D. Anderson. It should be refrigerated immediately when you receive it. You will drink an 8-ounce (1 cup) pomegranate liquid extract or placebo each day (7 days a week) for 52 weeks (about 1 year). All bottles of the study drink should be refrigerated until you are ready to drink it. You will receive detailed instructions on how to drink the study drink when you receive your first week's supply. You will continue to drink the study drink for 52 weeks or until your PSA levels do not appear to be responding.

A telephone call will be made approximately 7 days after your screening visit. At this time, you will be informed of your eligibility to participate in the study, and that you have been randomized. You will be informed of the delivery date for your study drink and a study-product consumption diary.

During this study, you will be asked to return to the clinic every 13 weeks (Weeks 13, 26, 39, and 52). You will see the research nurse at Weeks 13, 26, and 39, and you will see the study doctor at Week 52. During these visits, you will have a physical exam, including measurement of your vital signs and weight. You will be asked if you are taking any medications. You will have blood drawn (about 3 to 4 teaspoons) and urine collected for routine tests. You will be asked if you have been drinking the study drink each day. You will be given a study-product consumption diary with instructions to record that you drank the drink daily. It will be given to you at each 13-week follow-up visit. You will be asked not to begin or to stop taking any new nutritional or dietary supplements while you are on this study so that your supplements do not interfere with the effects of the study drink.

If the disease gets worse while you are on study, you and your study doctor will be able to find out which study group you were in. If you were taking the placebo, you may be eligible to enter into another study where you will receive the pomegranate extract for up to 12 months.

During your last study visit (Week 52), you will have a physical exam, including measurement of your vital signs and weight. You will have a digital rectal exam. You will be asked about any medications you may be taking. You will have blood drawn (about 3 to 4 teaspoons) and urine collected for routine tests. You will be asked if you have been drinking the study drink each day for the last 13 weeks of the study (your consumption diary will be reviewed). You will be given another food-frequency questionnaire and QOL questionnaire like the ones that were given during screening.

This is an investigational study. Up to 200 participants will take part in this multicenter study. Up to 40 will be enrolled at M. D. Anderson.

• Drug: Pomegranate Juice
  Subjects will orally receive 8 ounces of pomegranate liquid extract (equivalent to 1.6 mmol of total polyphenols per day) or matching placebo daily.
  Other Name: PomWonderful
• Other: Placebo
  Subjects will orally receive 8 ounces of placebo liquid daily.
• Behavioral: Questionnaire
  Food-frequency questionnaires and quality of life questionnaires will be administered before and during the study.

• Experimental: Pomegranate liquid extract
  Subjects will orally receive 8 ounces of pomegranate liquid extract (equivalent to 1.6 mmol of total polyphenols per day) or matching placebo daily. Food-frequency questionnaires and quality of life questionnaires will be administered before and during the study.
  Interventions:

  • Drug: Pomegranate Juice
  • Behavioral: Questionnaire
• Placebo Comparator: Matching placebo juice
  Subjects will orally receive 8 ounces of placebo liquid daily. Food-frequency questionnaires and quality of life questionnaires will be administered before and during the study.
  Interventions:

  • Other: Placebo
  • Behavioral: Questionnaire

Inclusion Criteria:

1. Histologically confirmed adenocarcinoma of the prostate
2. Status post surgery, cryotherapy, or radiation therapy for the primary tumor
3. Documented rising serum PSA, including at least one of the following: absolute level of serum PSA >0.2 ng.mL following surgery; absolute level of serum PSA >1.0 ng/mL following radiation or cryotherapy; absolute level of serum PSA >/= 0.4 ng/mL for patients treated with multiple treatment modalities (e.g., surgery + radiation, radiation + cryotherapy, etc.) For the above PSA criteria, there must be 3 rising serum PSA time points over a minimum of 6 months above the minimum nadir achieved, and the entry serum PSA must be >/= 100% above the maximum nadir achieved
4. (Continued from 3) And must have both: 3 non-zero serum PSA measurements (including baseline) that are above the value reported after surgery, radiation cryotherapy or multiple treatment modalities; interval between seum PSA time points must be > 2 weeks
5. Performance status 0 or 1 on the ECOG scale
6. Minimum estimated life expectancy of 6 months
7. Subject must be eighteen years or older
8. Willingness and ability to sign an informed consent document
9. Agreement with complete abstinence from other commercially available pomegranate products during the course of the study
10. Use of dietary/herbal supplements (e.g., saw palmetto, selenium, etc) are acceptable provided the dose has been stable for at least 2 months prior to screening and the subject agrees not to change/stop during the course of the study

Exclusion Criteria:

1. Significant concomitant medical or psychiatric condition that, in the opinion of the investigator, would make the participant a poor protocol candidate
2. Hormonal therapy, with the exception of neoadjuvant androgen deprivation therapy (ADT) prior to or concurrent with primary therapy. Subjects who underwent neoadjuvant ADT must have a serum testosterone of >150 ng/mL at study entry
3. Concomitant or antecedent hormonal therapy for rising serum PSA after initial therapy of prostate cancer
4. Known allergy to pomegranate juice
5. Subjects unable or unwilling to comply with protocol requirements
6. Prior treatment with experimental drugs, high dose steroids, or with any drugs or therapy with the potential to impact prostate cancer or PSA within 6 months prior to the first dose of study product and for the duration of the study
7. Serum PSA > 7.0 ng/mL
8. Serum PSA doubling time </= 3 months or 24 > months
9. Evidence of metastatic disease on physical examination or on CT or bone scan
10. Use of finasteride, dutasteride at any point since primary therapy or during the study
11. Diabetes with a known HbA1c level > 7.0% during the past 3 months. Subjects with diabetes who have not had their HbA1c level measured during the last 3 months will have it tested at visit 1
12. Clinically significant abnormal laboratory value > 2X the upper limit of normal (2XULN)