A Pilot Phase II Study of Digoxin in Patients With Recurrent Prostate Cancer as Evident by a Rising PSA

Inclusion Criteria:

- There must be a confirmed biochemical progression. Biochemical progression is
defined as three rises in PSA levels, with each PSA determined at least 4 weeks
apart, and each PSA value increase >0.2 ng/ml.

- Baseline PSA must be determined within 4 weeks of study entry. At least 3 PSA values
are necessary prior to the study entry to calculate PSA doubling time (PSADT)
calculator.

- Men with history of radical prostatectomy are required to have baseline PSA >1 ng/ml.
Men treated with primary radiation therapy are required to have baseline PSA>2 ng/ml
and greater than 150% rise from postradiation nadir.

- PSA doubling time must be between 6 and 24 months.

- All treatments including intermittent hormonal therapy must have been discontinued
for > 6 months prior to study entry.

- No clinical or radiological evidence of distant metastases

- ECOG < 2 and adequate organ function

- Men with history of radical prostatectomy are required to have baseline PSA >1 ng/ml.
Men treated with primary radiation therapy are required to have baseline PSA>2 ng/ml
and greater than 150% rise from postradiation nadir

- Baseline PSA must be determined within 4 weeks of study entry. At least 3 PSA values
are necessary to calculate PSA doubling time via PSADT calculator at:
http://www.mskcc.org/mskcc/applications/nomograms/PSADoublingTime.aspx. PSA doubling
time must be between 6 and 24 months.

- All previous local modalities of treatment, including radiation and surgery, must
have been discontinued at least 8 weeks prior to treatment in this study. Patients
may have received prior systemic chemotherapy, hormonal therapy, biologic or vaccine
therapy. All systemic treatments must have been discontinued for > 6 months prior to
study entry.

- Patients receiving intermittent hormonal therapy for their rising PSA state are
considered eligible if testosterone level is above 150ng/dl and treatment was
discontinued > 6 months and agree not to have additional injections while on study
drug.

- No clinical or radiological evidence of distant metastases (excluding prostascint
scan/PET in absence of radiographic disease in Bone scan, CT scan or MRI if used).
Lymph node up to 2 cm size is allowed for the study.

- ECOG < 2 or Karnofsky Performance status >70% within 14 days before being registered
for protocol therapy (Appendix B)

- Normal organ function with acceptable initial laboratory values:

- Absolute neutrophil count ≥ 1 x 109/L

- Platelets > 50 x 109/L

- Creatinine <1.5 mg/dL

- Bilirubin <1.5 X ULN (institutional upper limits of normal)

- AST (SGOT) and ALT (SGPT) ≤ 1.5 x ULN

- Willingness to use adequate methods of contraception throughout study participation
and for at least 3 months after completing therapy

Exclusion Criteria:

- Metastatic disease or currently active second malignancy

- History of Sinus Node Disease and AV Block, Accessory AV Pathway
(Wolff-Parkinson-White Syndrome), history of Acute Myocardial Infarction.

- Electrolyte imbalance (hypokalemia, hypo- or hypercalcemia, hypomagnesemia)

- Severe pulmonary disease and hypoxia

- Medical conditions such as uncontrolled hypertension, uncontrolled diabetes mellitus,
active infectious hepatitis, type A, B or C, hypothyroidism or hyperthyroidism, which
would, in the opinion of the investigator, make this protocol unreasonably hazardous.

- Major thoracic or abdominal surgery within the prior 3 weeks.

- Patients with GI tract disease resulting in an inability to take oral medication,
malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures
affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's,
ulcerative colitis).

- Use of any prohibited concomitant medications: The washout period is at least 2 weeks
before starting the study.

- Insufficient time from last prior regimen or radiation exposure: Systemic therapies
for prostate cancer within 28 days prior to digoxin; strontium-89 within 12 weeks;
bicalutamide within 6 weeks.

- Persistent Grade >2 treatment-related toxicity from prior therapy

- History of any digoxin-related or drug induced anaphylactic reaction

- Receipt of another investigational agent within 6 months of study entry. Patient must
have recovered from all side effects of prior investigational therapy.