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

This study has been completed.
Sponsor:
Information provided by:
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00054106
First received: February 5, 2003
Last updated: November 7, 2010
Last verified: March 2010
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: buserelin
Drug: custirsen sodium
Drug: flutamide
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Study Start Date: December 2002
Study Completion Date: September 2008
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00054106

Locations
Canada, British Columbia
British Columbia Cancer Agency - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Sponsors and Collaborators
NCIC Clinical Trials Group
Investigators
Study Chair: Kim N. Chi, MD British Columbia Cancer Agency
  More Information

Additional Information:
Publications:
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.

ClinicalTrials.gov Identifier: NCT00054106     History of Changes
Other Study ID Numbers: I153, CAN-NCIC-IND153, ONCOGENEX-OGX-01-01, CDR0000269888
Study First Received: February 5, 2003
Last Updated: November 7, 2010
Health Authority: United States: Federal Government

Keywords provided by NCIC Clinical Trials Group:
adenocarcinoma of the prostate
stage III prostate cancer
stage II prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Buserelin
Flutamide
Hormones
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on April 15, 2014