Docetaxel and Prednisone With or Without OGX-011 in Treating Patients With Recurrent or Metastatic Prostate Cancer That Did Not Respond to Previous Hormone Therapy

Condition(s) targeted: Prostate Cancer

Intervention: OGX-011 (Drug); docetaxel (Drug); prednisone (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: National Cancer Institute of Canada

Official(s) and/or principal investigator(s):
Kim N. Chi, MD, Study Chair, Affiliation: British Columbia Cancer Agency

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.

Official title: 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

Study design: Treatment, Randomized, Open Label

Primary outcome: Prostate-specific antigen (PSA) response measured by Bubley criteria at completion of study

Secondary outcome:

Toxicity

Time to treatment failure

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

Criteria:

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

Cross Cancer Institute at University of Alberta, Edmonton, Alberta T6G 1Z2, Canada

Tom Baker Cancer Centre - Calgary, Calgary, Alberta T2N 4N2, Canada

British Columbia Cancer Agency - Centre for the Southern Interior, Kelowna, British Columbia V1Y 5L3, Canada

British Columbia Cancer Agency - Vancouver Cancer Centre, Vancouver, British Columbia V5Z 4E6, Canada

CancerCare Manitoba, Winnipeg, Manitoba R3E 0V9, Canada

Saint John Regional Hospital, Saint John, New Brunswick E2L 4L2, Canada

Nova Scotia Cancer Centre, Halifax, Nova Scotia B3H 1V7, Canada

London Regional Cancer Program at London Health Sciences Centre, London, Ontario N6A 4L6, Canada

Margaret and Charles Juravinski Cancer Centre, Hamilton, Ontario L8V 5C2, Canada

Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada

Toronto Sunnybrook Regional Cancer Centre at Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada

Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec H2L-4M1, Canada

Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: June 2005
Last updated: May 23, 2008