Prostate Cancer Prevention Study for Men With High Grade PIN (Prostatic Intraepithelial Neoplasia)
Condition: Preneoplastic Conditions; Prostatic Intraepithelial Neoplasia
MeSH terms: Neoplasms; Carcinoma in Situ; Prostatic Intraepithelial Neoplasia; Precancerous Conditions
Intervention: Toremifene 20 mg; Placebo
Intervention description: The subject takes one dose by mouth of the 20mg Toremifine Citrate tablet once a day for the length of the trial (360 days).; The subject takes a placebo tablet identical in appearance to the toremifene 20mg tablet, administered by mouth daily for 360 days.
Intervention MeSH terms: Toremifene
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 1589.0
Sex: Male
Minimum age: 30 Years
Healthy volunteers: No
Keywords: neoplasia; chemoprevention; cancer; premalignant; precancerous; Chemoprophylaxis; Intraepithelial Prostatic Neoplasia; Neoplasia, Prostatic Intraepithelial

Summary:

      The purpose of this study is to determine if toremifene citrate is effective and safe in the
      prevention of prostate cancer in men who have been diagnosed with high grade prostatic
      intraepithelial neoplasia (PIN).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Give voluntary signed informed consent in accordance with institutional policies

          -  Be male, aged ≥ 30 years

          -  Have a diagnosis of high grade PIN from any previous prostate biopsy. The diagnosis of
             high grade PIN must be confirmed by the central pathologist

          -  Have had a prostate biopsy in the last 6 months with a minimum of 10 cores that shows
             no evidence of cancer as confirmed by the central pathologist; OR, have had 2 prostate
             biopsies (each with a minimum of 6 cores) in the 12 months prior to screening with at
             least one of the biopsies occurring within 6 months prior to the screening visit. Both
             biopsies should have no evidence of cancer as confirmed by the central pathologist

          -  Have a serum PSA of ≤ 10 ng/mL

          -  Agree to provide tablet containers for tablet counts and to complete a daily diary of
             study drug intake

          -  Agree to use an effective method of contraception, if the partner is of child-bearing
             age, while on study and for 30 days after the last dose of study medication

          -  Have adequate bone marrow, liver and renal function:

               -  White Blood Cell (WBC) Count ≥ 3,000/mm3;

               -  Platelet Count ≥ 100,000/mm3;

               -  Bilirubin ≤ 1.5 mg/dL;

               -  AST and ALT < 2x upper limit of normal;

               -  Serum Creatinine ≤ 2.0 mg%

        Exclusion Criteria:

          -  Previous exposure to toremifene citrate

          -  Have evidence of prostate cancer (local, regional and/or distal metastasis)

          -  Have any history of other malignancies (Exceptions include non-melanoma skin cancer or
             other cancer that has no evidence of tumor reoccurrence 5 years after definitive
             treatment).

          -  Have active systemic viral, bacterial, or fungal infections requiring treatment

          -  Have, in the judgment of the investigator, a clinically significant concurrent illness
             or psychological, familial, sociological, geographical or other concomitant condition
             that would not permit adequate follow-up and compliance with the study protocol

          -  Concurrently being treated with other investigational agents or have participated in
             an investigational study within 60 days prior to screening

          -  Currently taking dutasteride. Subject is eligible if he stops dutasteride for a total
             washout of 90 days prior to the Screening Visit and agrees not to use dutasteride for
             the duration of the study.

          -  Have previously taken finasteride for greater than two years

          -  Currently taking finasteride. Subject is eligible if he stops finasteride for a total
             washout of 30 days prior to the Screening Visit and agrees not to use finasteride for
             the duration of the study.

          -  Currently taking testosterone or testosterone-like supplements, such as
             dehydroepiandrosterone (DHEA). Subject is eligible if he stops these agents for a
             total washout of 30 days prior to the Screening Visit and agrees not to use these
             agents for the duration of the study.

          -  Have a history of taking PC-SPES within the past two years.

          -  Currently taking herbal medicine or dietary supplements for prostate health, such as
             Saw Palmetto (also known as Serenoa Repens).

        Subject is eligible if he stops these agents for a total washout of 30 days prior to taking
        the first dose of study drug and agrees not to use these agents for the duration of the
        study.

        Lycopene, vitamin E and selenium are not prohibited and no washout is required. However,
        vitamin E intake should be limited to less than 400 i.u. per day.

          -  Have a history of thromboembolic event or disease including deep vein thrombosis,
             pulmonary embolus, or thrombotic stroke

          -  History of chronic hepatitis or cirrhosis