Quinacrine Treatment in Patients With Androgen-Independent Prostate Cancer

Prostatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00417274
• Other study ID #: CBL-DD-05-C-H-2003
• Status: Completed
• Phase: Phase 2
• First received: December 27, 2006
• Last updated: March 6, 2013
• Start date: December 2006
• Est. completion date: May 2008

Study information

• Verified date: September 2012
• Source: Cleveland BioLabs
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: May 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Prostatic Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Quinacrine
100 mg daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Cleveland BioLabs

References & Publications (1)

Gurova KV, Hill JE, Guo C, Prokvolit A, Burdelya LG, Samoylova E, Khodyakova AV, Ganapathi R, Ganapathi M, Tararova ND, Bosykh D, Lvovskiy D, Webb TR, Stark GR, Gudkov AV. Small molecules that reactivate p53 in renal cell carcinoma reveal a NF-kappaB-dependent mechanism of p53 suppression in tumors. Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17448-53. Epub 2005 Nov 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of Quinacrine, Based on Prostate Specific Antigen (PSA) Response in Patients With Androgen-independent Metastatic Prostate Cancer	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	No