- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00417274
Quinacrine Treatment in Patients With Androgen-Independent Prostate Cancer
An Open-Label, Phase II Safety, Tolerability, Drug Level and Efficacy Trial of Quinacrine in Patients With Androgen-Independent Metastatic Prostate Cancer
Study Overview
Detailed Description
Despite a modest improvement in survival with available chemotherapy treatments, androgen-independent metastatic prostate cancer remains essentially incurable.
Several changes in gene function that characterize malignancy have been identified. For example the p53 gene in normal tissue lessens the risk of cancer through growth arrest or cell suicidal programs. Thus the silenced p53 gene present in cancer tissue contributes to the growth of the cancer. In addition when the p53 gene is silenced, a cell survival pathway, controlled by the NF-kB gene, is activated leading increased cell survival.
Quinacrine can activate p53 and inhibit NF-kB, thus reestablishing cell suicidal programs and decreasing cell survival in cancer tissue. Moreover, quinacrine is effective against several prostate tumor cell lines in vitro, and has anti-tumor effects against prostate cancer xenografts in mice.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients must be males, at least 18 years of age, with pathologically confirmed adenocarcinoma of the prostate
Patients must have evidence of androgen-independent metastatic prostate cancer (AIMPC) following standard antiandrogen withdrawal. AIMPC will be defined as the category of patients with metastatic prostate cancer with radiologic evidence of metastases (bone scan, CT, etc.) and castrate levels of testosterone (~ 50 ng/dL).
- All patients must be receiving ongoing therapy to ensure testicular androgen suppression (LHRH agonists therapy or bilateral orchiectomy).
- All patients receiving anti-androgen therapy [e.g., flutamide (Eulexin), bicalutamide (Casodex), or nilutamide (Nilandron)] must have initiated therapy at least 3 months (90 days) prior to the Baseline visit.
- Patients must have received prior docetaxel-based or mitoxantrone-based chemotherapy, or refused or been ineligible for chemotherapy. Previous chemotherapy treatments must be completed at least 4 week prior to Screening, and patients must not have any residual therapy-related toxicities present at Screening.
Patients must have evidence of disease progression defined as any of the following:
- New sites of metastatic disease on radiographic imaging (bone scan or CT scan of chest/abdomen/pelvis) as determined by the referring physician.
- PSA progression, defined as a 50% or greater rise in PSA value over a baseline level of at least 1.0 ng/mL, confirmed after an interval of at least two weeks.
- ECOG performance status 0-2 (see Appendix 4)
Patients must have adequate organ and bone marrow function as defined below:
- Absolute neutrophil count greater than 1500/mL
- Platelets greater than 100,000/mL
- Serum creatinine less than 2.0 mg/dL
- Total bilirubin less than 1.5 mg/dL
- AST (SGOT) and ALT (SGPT) less than 2 times the ULN [less than 5 times the ULN if liver metastases are present].
- Sexually active men whose sexual partners are women of childbearing potential must agree to use a medically acceptable form of barrier contraception or abstinence during their participation in the study and for at least six weeks after study drug discontinuation.
- Written informed consent/HIPAA authorization must be provided prior to the performance of any study-related procedures.
Exclusion Criteria:
- Prior allergic reactions or a history of intolerance attributed to quinacrine or other acridine derivatives
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, hematological disorders, hepatic disease, or psychiatric illness/social situations that would limit compliance with study requirements.
- Lifetime history of porphyria or psoriasis
- Documented glucose-6-phosphate dehydrogenase deficiency
- Lifetime history of seizure disorder (except infant febrile seizures)
- Lifetime history of schizophrenia, bipolar disorder, or any other psychotic disorders.
- Lifetime history of dermatitis as an allergic/toxic reaction to any medication
- Clinical evidence of CNS metastases
- Patients with a history of any malignancy (other than basal, squamous cell cancers and Ta bladder cancers) within 5 years of baseline visit
- Any grade 2 sensory neuropathy
- QTc (Bazett) >450 msec
- Patients with NYHA class 3 or 4 failure
- Patients with myocardial infarction or acute coronary syndrome within the previous 6 months
- Patients who require anti-arrhythmic treatment
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Quinacrine
Uncontrolled treatment arm
|
100 mg daily
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy of Quinacrine, Based on Prostate Specific Antigen (PSA) Response in Patients With Androgen-independent Metastatic Prostate Cancer
Time Frame: End of treatment
|
Patients who achieved a complete response (CR) or a partial response (PR) to therapy were allowed to continue to receive treatment until disease progression or unacceptable toxicity occurred, until the patient discontinued treatment for another reason, or for a total of 6 months.
Patients who continued to show a CR or PR or who maintained stable disease (SD) after 6 months of therapy were to be allowed to continue therapy at the investigator's discretion.
|
End of treatment
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Edwin Posadas, MD, University of Chicago Hospitals
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Prostatic Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Antinematodal Agents
- Anthelmintics
- Antiplatyhelmintic Agents
- Anticestodal Agents
- Quinacrine
Other Study ID Numbers
- CBL-DD-05-C-H-2003
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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