Digoxin for Recurrent Prostate Cancer

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01162135
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 32
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Digoxin	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Phase II Study of Digoxin in Patients With Recurrent Prostate Cancer as Evident by a Rising PSA
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Open Label Pilot Study

Drug: Digoxin; 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.

Outcome Measures

Primary Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107

Sponsors and Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University

Investigators

• Principal Investigator: Jianqing Lin, MD, Thomas Jefferson University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospitals

Publications

None provided.

• Responsible Party: Sidney Kimmel Cancer Center at Thomas Jefferson University
• ClinicalTrials.gov Identifier: NCT01162135
• Other Study ID Numbers: 10G.87; 2009-43
• First Posted: Jul 14, 2010
• Last Update Posted: Nov 29, 2016
• Last Verified: Oct 1, 2016

• Keywords provided by Sidney Kimmel Cancer Center at Thomas Jefferson University: Digoxin; Recurrent Prostate Cancer; Prostate Specific Antigen
• Additional relevant MeSH terms: Prostatic Neoplasms; Digoxin

Study Results

Participant Flow

Arm/Group Title	Digoxin
Arm/Group Description	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
Period Title: Overall Study
STARTED	16
COMPLETED	13
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Digoxin
Arm/Group Description	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
Overall Participants	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.5 (9.5)
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 50%
>=65 years	8 50%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	16 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 12.5%
White	13 81.3%
More than one race	0 0%
Unknown or Not Reported	1 6.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 12.5%
Not Hispanic or Latino	14 87.5%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	16 100%

Outcome Measures

1. Primary Outcome

Title	Rate of Positive PSADT Outcome
Description	Proportion of patients at 6 months post-treatment with a PSADT >= 200% from baseline
Time Frame	6 months after treatment with digoxin

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Digoxin
Arm/Group Description	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
Measure Participants	13
Number [participants]	5 31.3%

Adverse Events

Arm/Group Title	Digoxin
Arm/Group Description	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
All Cause Mortality
	Digoxin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Digoxin
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Other (Not Including Serious) Adverse Events
	Digoxin
	Affected / at Risk (%)	# Events
Total	16/16 (100%)
Blood and lymphatic system disorders
Hyperkalemia	2/16 (12.5%)	4
Hyperglycemia	3/16 (18.8%)	6
Hypoglycemia	1/16 (6.3%)	2
Hypophosphatemia	1/16 (6.3%)	1
Lymphopenia	1/16 (6.3%)	1
Hyponatremia	1/16 (6.3%)	1
Hypomagnesemia	1/16 (6.3%)	1
Hyperbilirubinemia	1/16 (6.3%)	2
Bicarbonate low	1/16 (6.3%)	1
Hypertension	2/16 (12.5%)	3
Cardiac disorders
Bradycardia	1/16 (6.3%)	1
Heart palpitations	1/16 (6.3%)	1
EKG change	3/16 (18.8%)	4
Sinus brachycardia	1/16 (6.3%)	1
Gastrointestinal disorders
Epigastric discomfort	1/16 (6.3%)	1
Vomiting	2/16 (12.5%)	2
Indigestion	1/16 (6.3%)	1
Diarrhea	1/16 (6.3%)	1
Acid reflux	1/16 (6.3%)	1
Constipation	1/16 (6.3%)	1
General disorders
Dizziness	2/16 (12.5%)	2
Change in taste	1/16 (6.3%)	1
Incontinence	1/16 (6.3%)	1
Decreased appetite	2/16 (12.5%)	3
Cold/cough	3/16 (18.8%)	3
Fatigue	3/16 (18.8%)	3
Loose stools	2/16 (12.5%)	2
Decreased energy	1/16 (6.3%)	1
Lightheadedness	2/16 (12.5%)	2
Neck pain	2/16 (12.5%)	2
Arm pain	1/16 (6.3%)	1
Foot pain	1/16 (6.3%)	1
Numbness/cramping of lower legs	1/16 (6.3%)	1
Abdominal pain	1/16 (6.3%)	1
Nausea	2/16 (12.5%)	2
Headaches	1/16 (6.3%)	1
Back pain	2/16 (12.5%)	3
Vivid dreams	3/16 (18.8%)	3
Insomnia	2/16 (12.5%)	2
Low libido	1/16 (6.3%)	1
Side pain	1/16 (6.3%)	1
Rib pain	1/16 (6.3%)	1
Shoulder pain	1/16 (6.3%)	1
Tooth root canal	1/16 (6.3%)	1
Nightmares	1/16 (6.3%)	2
Hepatobiliary disorders
ALT high	2/16 (12.5%)	3
Infections and infestations
Tooth infection	1/16 (6.3%)	1
Musculoskeletal and connective tissue disorders
Arthritis	1/16 (6.3%)	1
Knee achiness	1/16 (6.3%)	2
Renal and urinary disorders
Hematuria	2/16 (12.5%)	4
Urinary tract infection	1/16 (6.3%)	1
Nocturia	1/16 (6.3%)	1
Reproductive system and breast disorders
Testicular soreness	1/16 (6.3%)	1
Erectile dysfunction	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection	2/16 (12.5%)	2
Difficulty raking deep breaths	1/16 (6.3%)	1
Skin and subcutaneous tissue disorders
Edema	2/16 (12.5%)	2
Boil on finger	1/16 (6.3%)	1
Poison ivy	1/16 (6.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.