Study of Recurrent Prostate Cancer With Rising Prostate Specific Antigen (PSA)

• Status: Completed
• Trial end date: 2012-06-01
• Target enrollment: 0
• Participant gender: Male

Summary

disulfiram is a DNA methyltransferase inhibitor that may provide benefit for patients with prostate cancer by restoring tumor suppressor genes.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Johns Hopkins University; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Treatments: Disulfiram

Criteria

Inclusion Criteria:

• Provide written informed consent and HIPAA authorization for the release of personal health information.

• Adult male ≥18 years of age

• No desire to drink any alcohol during the study period. (The potential for ethanol interactions may last 7 to 14 days. Patient is allowed to drink alcohol 2 weeks after the study is finished)

• Histological confirmed diagnosis of adenocarcinoma of the prostate (M0) with evidence of biochemical relapse after local therapy (i.e., surgery, radiation therapy, or both). Baseline PSA must be ≥ 1 ng/ml.

• There must be a confirmed rise in PSA shown by 2 PSA values at least 1 week apart, higher than a reference value noted within 12 months of study entry. Interim PSA values during the immediate pre-study 12-month interval may demonstrate a "fluctuation" including a decline; however the study baseline PSA must have show a rise within the pre-study 12-months period. 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.

• All previous local modalities of treatment, including radiation and surgery, must have been discontinued at least 4 weeks prior to treatment in this study. Patients may have received prior systemic chemotherapy, hormonal therapy, biologic or vaccine therapy

• 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 history of or current 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). Retroperitoneal/pelvic lymph node up to 2 cm size is allowed for the study.

• ECOG performance score < 2 within 14 days before being registered for protocol therapy

• Normal organ function with acceptable initial laboratory values:

• Absolute neutrophil count ≥ 1 x 109/L

• Platelets > 50 x 109/L

• Creatinine <2 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 alcohol dependence, seizures or psychoses.

• Medical conditions such as uncontrolled hypertension, uncontrolled diabetes mellitus, cardiac disease, active infectious hepatitis, type A, B or C, hypothyroidism, 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: Metronidazole, Amprenavir, Paraldehyde, Phenytoin, Coumadin, alcohol or alcohol-containing preparations, Isoniazid, Amitriptyline (please see Appendix B for other potential drug-drug interactions). 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 disulfiram; strontium-89 within 12 weeks; bicalutamide within 6 weeks.

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

• History of any disulfiram-related or drug induced anaphylactic reaction

• Receipt of another investigational agent within 28 days of study entry. Patient must have recovered from all side effects of prior investigational therapy