Phase II Metronomic Dosing, Etoposide, Cyclophosphamide, D0 Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Etoposide; Cyclophosphamide
Intervention description: 50 mg per day of Etoposide orally for 21 consecutive days. Etoposide will be alternated with oral cyclophosphamide. The drug is administered at night just prior to bed. Week 1 of each cycle will begin with etoposide.; 50 mg per day of cyclophosphamide orally for 21 consecutive days. Cyclophosphamide will be alternated with oral etoposide. The drug is taken 2 hours after breakfast. The patient will be asked to increase hydration throughout the day. Recommendation is at least 6, 8oz glasses of water or other non-caffeinated beverage. Week 4 of the each cycle will begin with cylcophosphamide. Chronic administration of cyclophosphamide at this dose has been well tolerated
Intervention MeSH terms: Cyclophosphamide; Etoposide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: prostate cancer; recurrent prostate cancer; stage IV prostate cancer

Summary:

      Based on data supporting the use of cyclophosphamide and etoposide both as single agents in
      combination and a Phase I study showing acceptable toxicity with a chronic dosing regimen, we
      propose a Phase II clinical trial. This protocol establishes a model that will test the
      hypothesis that the use of etoposide and cyclophosphamide early in the course of prostate
      cancer progression, when fewer tumor cells are present, will have greater anti-tumor
      activity. We plan to treat patients with stage D0 prostate cancer to assess toxicity and
      anti-tumor activity.
    

Eligibility criteria:

        Inclusion Criteria

          -  Patients with histologically proven prostate cancer and tumors limited to the prostate
             (including seminal vesicle involvement, provided all visible disease was surgically
             removed) that have completed local therapy and have an rising PSA value, as defined in
             Section 5.1.5.

          -  Prior androgen ablation therapy is allowed as long as the patient completed therapy at
             least 1 year prior to entry into this study. The patient must be fully recovered from
             such therapy and must not have demonstrated progression while on androgen ablation
             therapy.

          -  Primary treatment to the prostate (surgery and/or radiation) must have been completed
             at least 3 months prior to entry into this study and the patient must be fully
             recovered from such therapy.

          -  Patients must have a negative CT of the chest, abdomen and pelvis and bone scan. The
             scans must be completed within 4 weeks prior to the date of starting therapy.

          -  PSA value for patients enrolled must be > 2 ng/ml with a doubling time of £ 12 months.
             PSA value > 2 ng/ml must be documented by two measurements at least four weeks apart.
             The final PSA measurement before study entry must be obtained within one week prior to
             therapy. This will be considered the baseline PSA. (Note: The website
             http://www.mskcc.org/mskcc/html/10088.cfm may be used to access a prostate normogram
             calculator.)

          -  The following lab values must be obtained within 4 weeks prior to therapy:

          -  ANC ≥1500/mm³,

          -  Hemoglobin ≥ 10 g/dl

          -  Platelet count ≥ 100,000/mm³

          -  Serum creatinine ≤ 1.5 mg/dL

          -  Total bilirubin ≤ 1.5 mg/dL

          -  Liver function tests (SGOT, SGPT) ≤ 1.5 times the upper limit of the institution's
             normal range.

          -  Men ≥ 18 years of age.

          -  An estimated life expectancy of at least 6 months.

          -  ECOG performance status ≤ 2.

          -  Able to give informed, written consent.

          -  Men must consent to using effective contraception (barrier method- latex condom) while
             on treatment and for 4 weeks after discontinuation of treatment.

        Exclusion Criteria

          -  Patients with active infections or known infection with HIV (HIV testing will not be
             performed as part of this study).

          -  Any coexisting medical condition including uncontrolled cardiac, hepatic, renal or
             psychiatric disease defined as ³ Grade 3 (CTCAE Version 3).

          -  Concurrent use of other investigational agent.

          -  Patients that have previously received more than 2 months of therapy with any of the
             agents used in this study.

          -  PSA value < 2 ng/ml.

          -  Prior chemotherapy in the past 5 years.

          -  Use of androgen ablation therapy within 1 year, or history of progression on androgen
             ablation therapy.