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

NCT ID: NCT00054106

Last Updated: 2023-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-12-10
• Study Completion Date: 2008-09-22

Brief 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.

Detailed 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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

buserelin

Intervention Type: DRUG

custirsen sodium

Intervention Type: DRUG

flutamide

Intervention Type: DRUG

conventional surgery

Intervention Type: PROCEDURE

neoadjuvant therapy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kim N. Chi, MD

Role: STUDY_CHAIR

British Columbia Cancer Agency

Locations

British Columbia Cancer Agency - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Countries

Canada

References

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 Cancer Inst. 2005 Sep 7;97(17):1287-96. doi: 10.1093/jnci/dji252.

Reference Type: RESULT

PMID: 16145049 (View on PubMed)

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 Oncol 22 (Suppl 14): A-3033, 203s, 2004.

Reference Type: RESULT

Other Identifiers

CAN-NCIC-IND153

Identifier Type: OTHER

Identifier Source: secondary_id

ONCOGENEX-OGX-01-01

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000269888

Identifier Type: OTHER

Identifier Source: secondary_id

I153

Identifier Type: -

Identifier Source: org_study_id