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

Sponsor

NCIC Clinical Trials Group (Other)

Overall Status

Completed

CT.gov ID

NCT00258388

Collaborator

(none)

Enrollment

Locations

Arms

66.7

Actual Duration (Months)

6.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: custirsen sodium Drug: docetaxel Drug: prednisone	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

82 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 27, 2005

Actual Primary Completion Date :

Nov 8, 2007

Actual Study Completion Date :

Jan 18, 2011

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Prostate-specific antigen (PSA) response measured by Bubley criteria at completion of study [2 years]

Secondary Outcome Measures

Toxicity [2 years]
Time to treatment failure [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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