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

NCT01118741 | Completed Results DMC

• 1 other identifier: J0972
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Prostate Cancer

Keywords

Rising PSA; Recurrent Non Metastatic Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Proportion of Subjects With a Demethylation Response at Each Dose Level

  For both of the doses explored (i.e. disulfiram 250 mg PO daily and 500 mg PO daily) the proportion of subjects with a demethylation response was computed. A demethylation response was defined as a \>=10% decrease from baseline in global 5-methyl cytosine content as assessed from peripheral blood mononuclear cells.

  24 months

Secondary Outcomes (1)

• Clinical Response

  Up to 6 months

Interventions

Disulfiram DRUG

Cohort 1: 250mg PO daily for 28 days Cohort 2: 500mg PO daily for 28 days

Also known as: Antabuse

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (3)

Johns Hopkins Hospital

Baltimore, Maryland, 21231, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Thomas Jefferson Universith

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Disulfiram

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Ditiocarb; Thiocarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Disulfides; Sulfides; Sulfur Compounds

Results Point of Contact

• Title: Michael Carducci, MD
• Organization: Johns Hopkins University

carducci@jhmi.edu

410-614-3977

Study Officials

• Michael A Carducci, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2010
• First Posted: May 7, 2010
• Study Start: May 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: June 12, 2018
• Results First Posted: June 6, 2014

Record last verified: 2018-05

Locations

US (3)