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

NCIC Clinical Trials Group

Status and phase

Completed

Phase 1

Conditions

Prostate Cancer

Treatments

Procedure: conventional surgery

Drug: flutamide

Drug: buserelin

Procedure: neoadjuvant therapy

Drug: custirsen sodium

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT00054106

I153

CAN-NCIC-IND153 (Other Identifier)

CDR0000269888 (Other Identifier)

ONCOGENEX-OGX-01-01 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

25 patients

Sex

Male

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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