Quinacrine Treatment in Patients With Androgen-Independent Prostate Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cleveland BioLabs
ClinicalTrials.gov Identifier:
NCT00417274
First received: December 27, 2006
Last updated: March 6, 2013
Last verified: September 2012
  Purpose

The purpose of this study is to determine whether quinacrine is effective in the treatment of Androgen-Independent Prostate Cancer.


Condition Intervention Phase
Prostatic Cancer
Drug: Quinacrine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Phase II Safety, Tolerability, Drug Level and Efficacy Trial of Quinacrine in Patients With Androgen-Independent Metastatic Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Cleveland BioLabs:

Primary Outcome Measures:
  • Efficacy of Quinacrine, Based on Prostate Specific Antigen (PSA) Response in Patients With Androgen-independent Metastatic Prostate Cancer [ Time Frame: End of treatment ] [ Designated as safety issue: No ]
    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.


Enrollment: 31
Study Start Date: December 2006
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Quinacrine
Uncontrolled treatment arm
Drug: Quinacrine
100 mg daily
Other Name: CBLB102

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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).

    1. All patients must be receiving ongoing therapy to ensure testicular androgen suppression (LHRH agonists therapy or bilateral orchiectomy).
    2. 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:

    1. New sites of metastatic disease on radiographic imaging (bone scan or CT scan of chest/abdomen/pelvis) as determined by the referring physician.
    2. 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:

    1. Absolute neutrophil count greater than 1500/mL
    2. Platelets greater than 100,000/mL
    3. Serum creatinine less than 2.0 mg/dL
    4. Total bilirubin less than 1.5 mg/dL
    5. 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00417274

Sponsors and Collaborators
Cleveland BioLabs
Investigators
Principal Investigator: Edwin Posadas, MD University of Chicago Hospitals
  More Information

Publications:
Responsible Party: Cleveland BioLabs
ClinicalTrials.gov Identifier: NCT00417274     History of Changes
Other Study ID Numbers: CBL-DD-05-C-H-2003
Study First Received: December 27, 2006
Results First Received: June 28, 2011
Last Updated: March 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Cleveland BioLabs:
Cancer of Prostate
Prostate Cancer
Cancer of the Prostate
Neoplasms, Prostate
Neoplasms, Prostatic
Prostate Neoplasms
Prostatic Cancer
Androgen-Independent Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Androgens
Quinacrine
Anthelmintics
Anti-Infective Agents
Anticestodal Agents
Antimalarials
Antinematodal Agents
Antineoplastic Agents
Antiparasitic Agents
Antiplatyhelmintic Agents
Antiprotozoal Agents
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014