Docetaxel and Prednisone With/Out OGX-011 in Recurrent or Metastatic Prostate Cancer That Did Not Respond to Previous Hormone Therapy

A Randomized Phase II Study of OGX-011 in Combination With Docetaxel and Prednisone or Docetaxel and Prednisone Alone in Patients With Metastatic Hormone Refractory Prostate Cancer

RATIONALE: Drugs used in chemotherapy, such as docetaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. OGX-011 may help docetaxel and prednisone kill more tumor cells by making tumor cells less resistant to the drugs.

PURPOSE: This randomized phase II trial is studying how well giving docetaxel and prednisone with or without OGX-011 works in treating patients with recurrent or metastatic prostate cancer that did not respond to previous hormone therapy.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: custirsen sodium; Drug: docetaxel; Drug: prednisone

Detailed Description

OBJECTIVES:

Primary

• Determine the efficacy, in terms of prostate-specific antigen response, of docetaxel and prednisone with or without OGX-011 in patients with hormone-refractory locally recurrent or metastatic prostate cancer.

Secondary

• Determine the objective response rate and duration in patients treated with these regimens.
• Determine the safety and toxic effects of these regimens in these patients.
• Determine the overall and progression-free survival of patients treated with these regimens.

OUTLINE: This is a multicenter, randomized, open-label study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive a loading dose of OGX-011 IV over 2 hours on days -7, -5, and -3. Patients then receive OGX-011 IV over 2 hours on days 1, 8, and 15, docetaxel IV over 1 hour on day 1, and oral prednisone twice daily on days 1-21. Treatment repeats every 3 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive docetaxel IV over 1 hour on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 3 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Calgary, Canada, T2N 4N2
    • Tom Baker Cancer Centre
  • Edmonton, Canada, T6G 1Z2
    • Cross Cancer Institute
  • Halifax, Canada, B3H 1V7
    • QEII Health Sciences Center
  • Hamilton, Canada, L8V 5C2
    • Juravinski Cancer Centre at Hamilton Health Sciences
  • Kelowna, Canada, V1Y 5L3
    • BCCA - Cancer Centre for the Southern Interior
  • London, Canada, N6A 4L6
    • London Regional Cancer Program
  • Montreal, Canada, H2L 4M1
    • CHUM - Hopital Notre-Dame
  • Saint John, Canada, E2L 4L2
    • Atlantic Health Sciences Corporation
  • Toronto, Canada, M5G 2M9
    • Univ. Health Network-Princess Margaret Hospital
  • Toronto, Canada, M4N 3M5
    • Odette Cancer Centre
  • Vancouver, Canada, V5Z 4E6
    • BCCA - Vancouver Cancer Centre
  • Winnipeg, Canada, R3E 0V9
    • CancerCare Manitoba
• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the prostate

  • Metastatic or locally recurrent disease
• Not curable with standard therapy

• Systemic chemotherapy is indicated, due to disease progression while receiving androgen-ablative therapy (i.e., hormone-refractory disease)

  • Disease progression is defined as development of new metastatic lesions OR ≥ 2 consecutive rises in prostate-specific antigen (PSA) over a reference value

  • Androgen ablative therapy must have included either medical or surgical castration

    • Castrate level of testosterone (≤ 1.7 nmol/L) required if treated with medical androgen ablation
  • Patients with documented disease progression while on peripheral antiandrogens must also have documented PSA progression after stopping antiandrogens
• PSA ≥ 5 ng/mL
• No known CNS metastases

PATIENT CHARACTERISTICS:

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No known bleeding disorder

Hepatic

• PT and PTT or INR normal
• Bilirubin normal
• AST and ALT ≤ 1.5 times upper limit of normal (ULN)

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No significant cardiac dysfunction

Other

• Fertile patients must use effective contraception
• No pre-existing peripheral neuropathy ≥ grade 2
• No active, uncontrolled infection
• No significant neurological disorder that would preclude study compliance
• No history of other malignancies within the past 5 years except adequately treated nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Chemotherapy

• No prior chemotherapy except estramustine and recovered
• No other concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics
• At least 4 weeks since prior antiandrogens (6 weeks for bicalutamide)
• Luteinizing hormone-releasing hormone (LHRH) agonist therapy must be continued* or restarted* during study treatment to maintain castrate levels of testosterone NOTE: *For patients receiving LHRH agonist therapy prior to study entry

Radiotherapy

• At least 4 weeks since prior external beam radiotherapy except low-dose, nonmyelosuppressive radiotherapy

  • Must have had less than 25% of marrow irradiated
• No prior strontium chloride Sr 89
• No concurrent radiotherapy except low-dose, nonmyelosuppressive, palliative radiotherapy

Surgery

• At least 2 weeks since prior major surgery

Other

• At least 4 weeks since prior investigational agent
• At least 4 weeks since prior anticancer therapy
• No concurrent therapeutic anticoagulants except low-dose oral anticoagulants (i.e., 1 mg warfarin) or low molecular weight heparin
• No other concurrent investigational agents
• No other concurrent cytotoxic therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: OGX011, Docetaxel and Prednisone	Drug: custirsen sodium; 640mg IV for 2 hours - Cycle 1: Days -7, -5, -3, 1, 8, 15 (4 week cycle) Subsequent cycles: weekly on days 1, 8, 15 (3 week cycles); Drug: docetaxel; 75mg/m2 IV for 1 hour - Day 1 every 3 weeks (3 week cycles); Drug: prednisone; 5mg PO BID
Active Comparator: Docetaxel plus prednisone	Drug: docetaxel; 75mg/m2 IV for 1 hour - Day 1 every 3 weeks (3 week cycles); Drug: prednisone; 5mg PO BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Prostate-specific antigen (PSA) response measured by Bubley criteria at completion of study	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Toxicity	2 years
Time to treatment failure	2 years

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Investigators: Study Chair: Kim N. Chi, MD, British Columbia Cancer Agency

Publications and helpful links

General Publications

• Chi KN, Hotte SJ, Yu EY, Tu D, Eigl BJ, Tannock I, Saad F, North S, Powers J, Gleave ME, Eisenhauer EA. Randomized phase II study of docetaxel and prednisone with or without OGX-011 in patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2010 Sep 20;28(27):4247-54. doi: 10.1200/JCO.2009.26.8771. Epub 2010 Aug 23.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2005
• Primary Completion (Actual): November 8, 2007
• Study Completion (Actual): January 18, 2011

Study Registration Dates

• First Submitted: November 22, 2005
• First Submitted That Met QC Criteria: November 22, 2005
• First Posted (Estimated): November 24, 2005

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: stage IV prostate cancer; recurrent prostate cancer; adenocarcinoma of the prostate
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Docetaxel; Prednisone
• Other Study ID Numbers: I165; CAN-NCIC-IND165 (Other Identifier: PDQ); ONCOGENEX-OGX-011-03 (Other Identifier: Oncogenex Technologies); FHCRC-6084 (Other Identifier: Fred Hutchinson Cancer Research Center); UWCC-UW-6084 (Other Identifier: University of Washington); UWCC-06-0499-H/D (Other Identifier: University of Washington); CDR0000450846 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No