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An Open-Label, Phase II Safety, Tolerability, Drug Level and Efficacy Trial of Quinacrine in Patients With Androgen-Independent Metastatic Prostate Cancer

Phase 2
18 Years
Not Enrolling
Prostatic Cancer

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Trial Information

An Open-Label, Phase II Safety, Tolerability, Drug Level and Efficacy Trial of Quinacrine in Patients With Androgen-Independent Metastatic Prostate Cancer

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.

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

- 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

- 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

- Patients who require anti-arrhythmic treatment

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Efficacy of Quinacrine, Based on Prostate Specific Antigen (PSA) Response in Patients With Androgen-independent Metastatic Prostate Cancer

Outcome Description:

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.

Outcome Time Frame:

End of treatment

Safety Issue:


Principal Investigator

Edwin Posadas, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Hospitals


United States: Food and Drug Administration

Study ID:




Start Date:

December 2006

Completion Date:

May 2008

Related Keywords:

  • Prostatic Cancer
  • Cancer of Prostate
  • Prostate Cancer
  • Cancer of the Prostate
  • Neoplasms, Prostate
  • Neoplasms, Prostatic
  • Prostate Neoplasms
  • Prostatic Cancer
  • Androgen-Independent Prostate Cancer
  • Prostatic Neoplasms