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

Sponsor:	NCIC Clinical Trials Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00054106

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 I

Study Type:	Interventional
Study Design:	Treatment, Open Label
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:

MedlinePlus related topics: Cancer Prostate Cancer Surgery

Drug Information available for: Flutamide Buserelin Buserelin acetate OGX-011

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

December 2002

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:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

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.

Study ID Numbers:	CDR0000269888, CAN-NCIC-IND153, ONCOGENEX-OGX-01-01
Study First Received:	February 5, 2003
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00054106 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the prostate
stage III prostate cancer
stage II prostate cancer

Additional relevant MeSH terms:

Buserelin
Antineoplastic Agents, Hormonal
Genital Neoplasms, Male
Prostatic Diseases
Antineoplastic Agents
Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Urogenital Neoplasms
Reproductive Control Agents

Genital Diseases, Male
Flutamide
Pharmacologic Actions
Androgen Antagonists
Neoplasms
Neoplasms by Site
Therapeutic Uses
Fertility Agents, Female
Fertility Agents
Prostatic Neoplasms

ClinicalTrials.gov processed this record on November 27, 2009