Hormone Therapy and OGX-011 Before Radical Prostatectomy in Treating Patients With Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

A Phase I Study Of Combination Neoadjuvant Hormone Therapy And Weekly OGX-011 (Clusterin Antisense Oligonucleotide) Prior To Radical Prostatectomy In Patients With Localized Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00054106
• Other study ID #: I153
• Secondary ID: CAN-NCIC-IND153O
• Status: Completed
• Phase: Phase 1
• Start date: December 10, 2002
• Est. completion date: September 22, 2008

Study information

• Verified date: April 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Drugs such as flutamide and buserelin may stop the adrenal glands from producing androgens. OGX-011 may help flutamide and buserelin kill more tumor cells by making tumor cells more sensitive to the drugs. Giving flutamide and buserelin with OGX-011 before surgery may shrink the tumor so it can be removed during surgery.

PURPOSE: Phase I trial to study the effectiveness of combining hormone therapy with OGX-011 before radical prostatectomy in treating patients who have prostate cancer.

Description:

OBJECTIVES:

• Determine the maximum tolerated dose and recommended phase II dose of OGX-011 (clusterin antisense oligonucleotide) when administered with neoadjuvant hormonal therapy before radical prostatectomy in patients with adenocarcinoma of the prostate.

• Determine the toxicity of this regimen in these patients.

• Determine the pharmacokinetics of OGX-011 when this regimen is administered in these patients..

• Assess the effects of this regimen on pathologic complete response rates in these patients.

• Correlate plasma and/or prostate concentrations of OGX-011 with patient response or toxicity measures.

OUTLINE: This is a dose-escalation study of OGX-011.

Patients receive OGX-011 IV over 2 hours on days 1, 3, 5, 8, 15, 22, and 29; oral flutamide three times daily for 4 weeks; and buserelin subcutaneously on day 1.

Cohorts of 3-6 patients (except for 1 patient at starting dose) receive escalating doses of OGX-011 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The recommended phase II dose is the dose preceding the MTD.

Patients undergo radical prostatectomy and bilateral pelvic lymphadenectomy 1 week after the last dose of neoadjuvant therapy.

Patients are followed at 7 days after surgery and then at 3 months.

PROJECTED ACCRUAL: Approximately 25-33 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: September 22, 2008
• Est. primary completion date: September 23, 2004
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

• High-risk, localized disease that is previously untreated

• Minimum of 2 positive biopsies

• Meets at least 1 of the following criteria:

• Stage T3

• Serum PSA greater than 10 ng/mL

• Gleason score 7-10

• Gleason score 6 and at least 3 positive biopsies

• Potential candidate for radical prostatectomy

PATIENT CHARACTERISTICS:

Age

• Over 18

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,000/mm^3

• Platelet count at least 100,000/mm^3

• Hemoglobin at least 10.0 g/dL

Hepatic

• Bilirubin normal

• AST and ALT normal

• PTT normal

• INR normal

Renal

• Creatinine normal

Cardiovascular

• No significant cardiac dysfunction

Other

• Fertile patients must use effective contraception

• No known hypersensitivity to oligonucleotides, luteinizing hormone-releasing hormone analogs, or anti-androgens

• No evidence of active uncontrolled infection

• No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer

• No other serious illness, psychiatric disorder, or medical condition that would preclude study compliance

• No history of a significant neurological disorder that would preclude informed consent

• No geographical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for prostate cancer

Endocrine therapy

• No prior hormonal therapy for prostate cancer

Radiotherapy

• No prior radiotherapy for prostate cancer

• No concurrent radiotherapy

Surgery

• Not specified

Other

• No concurrent heparin or warfarin anticoagulation

• No other concurrent investigational therapy

• No other concurrent cytotoxic therapy

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• buserelin

• custirsen sodium

• flutamide

Procedure:
• conventional surgery

• neoadjuvant therapy

Locations

Country	Name	City	State
Canada	British Columbia Cancer Agency - Vancouver Cancer Centre	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group

Country where clinical trial is conducted

Canada, 

References & Publications (2)

Chi KN, Eisenhauer E, Fazli L, et al.: A phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of OGX-011, a 2'methoxyethyl phosphorothioate antisense to clusterin, in patients with prostate cancer prior to radical prostatectomy. [Abstract] J Clin O

Chi KN, Eisenhauer E, Fazli L, Jones EC, Goldenberg SL, Powers J, Tu D, Gleave ME. A phase I pharmacokinetic and pharmacodynamic study of OGX-011, a 2'-methoxyethyl antisense oligonucleotide to clusterin, in patients with localized prostate cancer. J Natl — View Citation