Prostate Cancer
Conditions
Keywords
Digoxin, Recurrent Prostate Cancer, Prostate Specific Antigen
Brief summary
The purpose of this study is to assess the effectiveness of dioxin on prohibiting prostate cancer progression as measured by PSADT (prostate-specific antigen doubling time).
Detailed description
This is a pilot phase II, open labeled single center study to assess the efficacy of digoxin on inhibiting PCa progression as measured by PSADT. The participants will take study drug digoxin, which is approved by FDA for the treatment of CHF, 125 or 250 mcg orally daily, titrated to the level of 0.8 - 2 ng/ml for total of 6 cycles (4 weeks/cycle). The lower dose of digoxin (such as 125 mcg/day) will be chosen if serum level reaches 0.8 ng/ml already. Patients may continue another 6 cycles if evident of clinical benefit.
Interventions
DRUGDigoxin
The participants will take study drug digoxin, which is approved by FDA for the treatment of CHF, 125 or 250 mcg orally daily, titrated to the level of 0.8 - 2 ng/ml for total of 6 cycles (4 weeks/cycle). The lower dose of digoxin (such as 125 mcg/day) will be chosen if serum level reaches 0.8 ng/ml already. Patients may continue another 6 cycles if evident of clinical benefit. It is possible that some patients may need to receive 500 mcg per day to reach this targeted drug level. No further titration will be allowed beyond this FDA approved digoxin dose.
Sponsors
Sidney Kimmel Cancer Center at Thomas Jefferson University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Positive PSADT Outcome | 6 months after treatment with digoxin | Proportion of patients at 6 months post-treatment with a PSADT \>= 200% from baseline |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Digoxin Patients receive digoxin PO daily. Treatment repeats every 28 days for up to 6-12 courses in the absence of disease progression or unacceptable toxicity | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible | 1 |
| Overall Study | Severe back pain | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Digoxin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 67.5 years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Rate of Positive PSADT Outcome
Proportion of patients at 6 months post-treatment with a PSADT \>= 200% from baseline
Time frame: 6 months after treatment with digoxin
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Digoxin | Rate of Positive PSADT Outcome | 5 participants |