Evaluation of Safety and Feasibility of OGX-011 in Combination With 2nd-line Chemotherapy in Patients With HRPC

• Sponsor: Achieve Life Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00327340
• Collaborator: (none)
• Enrollment: 70
• Locations: 10
• Arms: 2
• Duration (Months): 51
• Patients Per Site: 7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is for patients with cancer of the prostate gland that has metastasized or spread outside the prostate to other parts of the body. Patients have already been treated with a drug called docetaxel or Taxotere® (with or without the addition of a steroid called prednisone) some time in the recent past. They either did not respond to this therapy or responded to this therapy, but now the cancer is progressing (growing larger or has spread to other areas of the body).

Custirsen (OGX-011) is an experimental drug that has been shown to increase the effectiveness of chemotherapy in several kinds of tumors, including prostate cancer.

Both docetaxel and mitoxantrone have anticancer activity in prostate and are approved by Health Canada and the Food and Drug Administration for the treatment of patients with prostate cancer.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: custirsen (OGX-011)/mitoxantrone; Drug: custirsen (OGX-011)/docetaxel	Phase 2

Detailed Description

This study was initiated as a multicenter, open-label, randomized study, with a planned enrollment of 40 subjects. Although two treatment arms were included in this study, no comparison between the arms was intended.

Subjects with metastatic HRPC who failed first-line docetaxel therapy and required second-line therapy were randomly assigned to treatment with OGX-011 in combination with docetaxel/prednisone (OGX-011/docetaxel/prednisone) or OGX-011 in combination with mitoxantrone/prednisone (OGX-011/mitoxantrone/ prednisone). The study was randomized to assure that subjects were enrolled in each of the two treatment arms in an unbiased manner.

Based on preliminary safety data from the first 44 subjects who were randomized to receive either docetaxel or mitoxantrone, the protocol was amended to enroll approximately 20 additional subjects who would be assigned to the docetaxel/prednisone treatment arm to further investigate safety of the combination.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Title: A Pilot Study Evaluating the Safety and Feasibility of Custirsen (OGX-011) in Combination With Second Line Chemotherapy in Patients With Hormone Refractory Prostate Cancer
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: OGX-011 / mitoxantrone/prednisone OGX-011 / mitoxantrone/prednisone: OGX-011 administered in combination with mitoxantrone and prednisone	Drug: custirsen (OGX-011)/mitoxantrone; All subjects began treatment with oral prednisone (5 mg twice daily, 10 mg/day) continued through completion of the final treatment cycle. Three IV administrations of OGX-011 (640 mg) were given as 2 hr infusions during the loading dose period (Days-9 to-1). Subjects were premedicated with either ibuprofen (400 mg) or acetaminophen (650 mg) 30 to 60 minutes prior to and every 4-6 hours for 24 hours following each of the three doses of OGX-011 during the loading dose period only. After the loading dose period, OGX-011 was given weekly on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone was administered IV on Day 1 of each cycle at a planned dose of 12 mg/m² infused over 30 minutes. Patients could receive a maximum of 9 cycles of treatment.; Other Names: custirsen OGX-011 TV-1011
Experimental: OGX-011/docetaxel/prednisone OGX-011/docetaxel/prednisone: OGX-011 administered in combination with docetaxel and prednisone	Drug: custirsen (OGX-011)/docetaxel; All subjects began treatment with oral prednisone (5 mg twice daily, 10 mg/day) continued through completion of the final treatment cycle. Three IV administrations of OGX-011 (640 mg) were given as 2 hr infusions during the loading dose period (Days-9 to -1). Subjects were premedicated with either ibuprofen (400 mg) or acetaminophen (650 mg) 30 to 60 minutes prior to and every 4-6 hours for 24 hours following each of the three doses of OGX-011 during the loading dose period only. After the loading dose period, OGX-011 was given weekly on Days 1, 8, and 15 of each 21 day cycle. Docetaxel was administered IV on Day 1 of each cycle at a planned dose of 75 mg/m² infused over 60 minutes. Patients could receive a maximum of 9 cycles of treatment.; Other Names: custirsen OGX-011 TV-1011

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability of Custirsen (OGX-011) in Combination With Either Docetaxel/Prednisone or Mitoxantrone/Prednisone as Second-line Chemotherapy. [Subjects were followed for safety from enrollment for up to 8 months (9 three-week cycles plus 30 days after end of treatment)]

   Safety and tolerability were based on Adverse Events (AE) and Serious Adverse Events (SAE) graded using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). The CTCAE has 5 grades with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1=Mild AE; Grade 2=Moderate AE; Grade 3=Severe AE; Grade 4=Life-threatening or disabling AE; and Grade 5=Death related to AE.

Secondary Outcome Measures

1. Feasibility of Treatment With Custirsen (OGX-011) in Combination With Second-line Chemotherapy Based on Prostate Specific Antigen (PSA) Response [PSA was evaluated at screening, on Day 1 of each cycle, at the end of treatment visit and during off-treatment follow up (up to 27 months)]

   PSA or prostate specific antigen is a marker for prostate cancer. A PSA response was defined as a decrease in PSA values of ≥ 50% relative to baseline on two or more consecutive measurements that were 4-6 weeks apart.

2. Feasibility of Treatment With OGX-011 in Combination With Either Docetaxel/Prednisone or Mitoxantrone/Prednisone as Second Line Chemotherapy Based on Time to Pain Progression [Enrollment until pain progression (up to 21 months)]

   Time to pain progression was defined as the time (months) from the first dose of OGX-011 to the first documentation of pain or analgesic progression or initiation of palliative radiation therapy. Pain response was defined as either a decrease of at least two points on the 11-point Worst Pain Scale, without an increase in analgesic level, maintained for at least two consecutive measurements approximately three weeks apart -or- a decrease in analgesic level, without an increase in pain score, maintained for at least two consecutive measurements approximately three weeks apart.

3. Relationship Between Changes in Serum Clusterin Levels and Change in Serum PSA Levels When OGX-011 in Combination With Either Docetaxel/Prednisone or Mitoxantrone/Prednisone is Administered as Second Line Chemotherapy. [Enrollment until disease progression (up to 13 months)]

   Serum clusterin samples were collected prior to receiving OGX-011 loading dose 1, prior to study treatment on Day 1 of each cycle, and at the end of treatment. PSA was evaluated at screening, on Day 1 of each cycle, at the end of treatment visit, and during off-treatment follow-up. PSA response was defined in the protocol as a decrease in PSA of ≥ 50% relative to baseline on two or more consecutive measurements 4-6 weeks apart.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age ≥ 18 years

2. Histologic diagnosis of adenocarcinoma of the prostate.

3. Metastatic disease on chest X-ray, bone scan, or computed tomography (CT) scan.

4. Failed after receiving a minimum of two cycles of a docetaxel based first line therapy regimen. Failure is defined as disease progression within 6 months of discontinuing first line docetaxel therapy. Disease progression is defined as one or more of the following:

• Progressive measurable (target) disease (by Response Evaluation Criteria in Solid Tumors [RECIST] criteria): at least a 20% increase in the sum of the longest diameters of measurable lesions (organ masses or lymph nodes) over the smallest sum observed (baseline or nadir) or the appearance of one or more new lesions as assessed by CT scan or chest X-ray.

• Bone scan progression: one or more new lesions on bone scan while on or following docetaxel treatment.

• Increasing serum PSA level: rise in PSA on three consecutive measurements obtained at least one week apart. If the third PSA value is less than the second, an additional fourth test to confirm a rising PSA will be acceptable.

1. Baseline laboratory values as stated below:

• Creatinine ≤ 1.5 x upper limit of normal (ULN)

• Bilirubin ≤ 1.1 x ULN (unless elevated secondary to conditions such as Gilbert's disease)

• SGOT (AST) ≤ 1.5 x ULN

• Castrate serum testosterone level (< 50 ng/mL-or-< 1.7 mmol/L).

1. If not treated with bilateral orchiectomy, patients must be willing to continue luteinizing hormone releasing hormone analogues throughout the study.

2. Adequate bone marrow function defined as absolute neutrophil count (ANC) ≥ 1.5 x 10^{9 cells/L and platelet count ≥ 100 x 10}9/L.

3. Karnofsky score ≥ 60

4. Received no other chemotherapy, radioisotope therapy, strontium 89, or samarium 153. (Prior radiotherapy and steroids following first line docetaxel therapy are allowed.)

5. Received no more than one prior biological response modifier therapy following first line docetaxel therapy.

6. At least 21 days since completing the last dose of docetaxel, biological response modifier, and/or radiotherapy. (Exception for radiotherapy: at least 7 days since completing a single fraction of ≤ 800 cGy to a restricted field.)

7. Has recovered from all therapy related toxicity to ≤ grade 2, (except alopecia and anemia.)

8. Willing and able to give informed consent and follow protocol requirements.

Exclusion Criteria:

1. Life expectancy less than 12 weeks.

2. Patient is beyond 6 months following the last dose of docetaxel.

3. Patient could not tolerate a dose of docetaxel of at least 45 mg/m² at the end of first line therapy due to toxicity.

4. History of or current documented brain metastasis or carcinomatous meningitis, treated or untreated. (Brain imaging in asymptomatic patients is not required.)

5. Current symptomatic cord compression requiring surgery or radiation therapy. (Once treated, patients are eligible for the study.)

6. Active second malignancy (except non melanomatous skin or superficial bladder cancer).

7. Prior radiotherapy to > 25% of the bone marrow.

8. Uncontrolled medical conditions such as a major active infection, myocardial infarction or stroke within 3 months, uncontrolled hypertension, and/or significant concurrent medical illness, that, in the opinion of the Investigator, would preclude protocol therapy.

9. History of or active congestive heart failure.

10. Known allergy or hypersensitivity to docetaxel or polysorbate 80 (diluent).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tom Baker Cancer Centre	Calgary	Alberta	Canada
2	Cross Cancer Institute	Edmonton	Alberta	Canada
3	BC Cancer Agency	Vancouver	British Columbia	Canada
4	CancerCare Manitoba	Winnipeg	Manitoba	Canada
5	QEII Health Sciences	Halifax	Nova Scotia	Canada
6	Juravinski Cancer Centre	Hamilton	Ontario	Canada
7	London Regional Cancer Program	London	Ontario	Canada
8	Toronto Sunnybrook	Toronto	Ontario	Canada
9	Jewish General Hospital	Montreal	Quebec	Canada
10	University of Montreal	Montreal	Quebec	Canada

Sponsors and Collaborators

• Achieve Life Sciences

Investigators

• Principal Investigator: Fred Saad, MD, FRCS, Université de Montréal
• Principal Investigator: Eric Winquist, MD, MSc, University of Western Ontario, Canada

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Achieve Life Sciences
• ClinicalTrials.gov Identifier: NCT00327340
• Other Study ID Numbers: OGX-011-07
• First Posted: May 18, 2006
• Last Update Posted: Oct 5, 2012
• Last Verified: Oct 1, 2012

• Keywords provided by Achieve Life Sciences: Metastatic hormone refractory prostate cancer (HRPC)
• Additional relevant MeSH terms: Prostatic Neoplasms; Docetaxel; Mitoxantrone

Study Results

Participant Flow

Recruitment Details	Participants were recruited at 10 institutions with a primary focus in oncology and located in Canada. The first subject was randomized on July 25, 2006. The last subject completed treatment on August 6, 2008 and the last survival follow-up visit was on August 13, 2010
Pre-assignment Detail	A total of 70 subjects were enrolled. 45 subjects were randomly assigned to treatment (21 to OGX-011/ docetaxel and 24 OGX-011/ mitoxantrone). An additional 25 subjects were enrolled under Amendment 2 and assigned to OGX-011/docetaxel retreatment. One subject was found to be ineligible and was not treated.

Arm/Group Title	OGX-011 / Mitoxantrone/Prednisone	OGX-011 / Docetaxel/Prednisone
Arm/Group Description	All subjects began with oral prednisone (5 mg twice daily)on Day-10. Custirsen (OGX-011) was infused intravenously over 2 hours on Day -7, -5 and-3 of cycle 1 (Pretreatment loading doses). OGX-011 was then infused for 2 hours on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone was infused at a dose of 12 mg/m² over 30 minutes on day 1 of each cycle.	All subjects began with oral prednisone (5 mg twice daily)on Day-10. Custirsen (OGX-011) was infused intravenously over 2 hours on Day -7, -5 and -3 of cycle 1 (Pretreatment loading doses). OGX-011 was then to be infused for 2 hours on Days 1, 8, and 15 of each 21-day cycle. Docetaxel was infused at a dose of 75 mg/m² over 60 minutes on day 1 of each cycle.
Period Title: Overall Study
STARTED	23	46
COMPLETED	8	16
NOT COMPLETED	15	30

Baseline Characteristics

Arm/Group Title	OGX-011 / Mitoxantrone/Prednisone	OGX-011 / Docetaxel/Prednisone	Total
Arm/Group Description	All subjects began with oral prednisone (5 mg twice daily)on Day-10. Custirsen (OGX-011) was infused intravenously over 2 hours on Day -7, -5 and-3 of cycle 1 (Pretreatment loading doses). OGX-011 was then infused for 2 hours on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone was infused at a dose of 12 mg/m² over 30 minutes on day 1 of each cycle.	All subjects began with oral prednisone (5 mg twice daily)on Day-10. Custirsen (OGX-011) was infused intravenously over 2 hours on Day -7, -5 and -3 of cycle 1 (Pretreatment loading doses). OGX-011 was then to be infused for 2 hours on Days 1, 8, and 15 of each 21-day cycle. Docetaxel was infused at a dose of 75 mg/m² over 60 minutes on day 1 of each cycle.	Total of all reporting groups
Overall Participants	23	46	69
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61	64	63
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	23 100%	46 100%	69 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 2.2%	1 1.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	3 6.5%	3 4.3%
White	21 91.3%	42 91.3%	63 91.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 8.7%	0 0%	2 2.9%
Karnofsky Score (participants) [Number]
60-70%	2 8.7%	6 13%	8 11.6%
80%	7 30.4%	13 28.3%	20 29%
90%	7 30.4%	22 47.8%	29 42%
100%	7 30.4%	5 10.9%	12 17.4%

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability of Custirsen (OGX-011) in Combination With Either Docetaxel/Prednisone or Mitoxantrone/Prednisone as Second-line Chemotherapy.
Description	Safety and tolerability were based on Adverse Events (AE) and Serious Adverse Events (SAE) graded using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE). The CTCAE has 5 grades with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1=Mild AE; Grade 2=Moderate AE; Grade 3=Severe AE; Grade 4=Life-threatening or disabling AE; and Grade 5=Death related to AE.
Time Frame	Subjects were followed for safety from enrollment for up to 8 months (9 three-week cycles plus 30 days after end of treatment)

Outcome Measure Data

Analysis Population Description

The total analysis population was 69 subjects: 70 subjects were enrolled; 45 were randomly assigned to treatment (24 to OGX-011/mitoxantrone and 21 to OGX-011 /docetaxel). An additional 25 subjects were assigned to OGX-011/docetaxel. One subject in the mitoxantrone arm was ineligible and did not receive study treatment.

Arm/Group Title	OGX-011 + Mitoxantrone + Prednisone	OGX-011 + Docetaxel + Prednisone
Arm/Group Description	custirsen (OGX-011) in combination with mitoxantrone and prednisone	custirsen (OGX-011) in combination with docetaxel and prednisone
Measure Participants	23	46
Percent of Subjects with Serious Adverse Events	26 113%	26 56.5%
Percent of Subjects with Grade 5 Adverse Events	13 56.5%	4 8.7%
Percent of Subjects with Grade 4 Adverse Events	26 113%	15 32.6%
Percent of Subjects with Grade 3 Adverse Events	70 304.3%	52 113%
Percent of Subjects with Grade 2 Adverse Events	83 360.9%	98 213%
Percent of Subjects with Grade 1 Adverse Events	100 434.8%	100 217.4%
Percent of Subjects who Discontinued Study Drug	22 95.7%	17 37%

2. Secondary Outcome

Title	Feasibility of Treatment With Custirsen (OGX-011) in Combination With Second-line Chemotherapy Based on Prostate Specific Antigen (PSA) Response
Description	PSA or prostate specific antigen is a marker for prostate cancer. A PSA response was defined as a decrease in PSA values of ≥ 50% relative to baseline on two or more consecutive measurements that were 4-6 weeks apart.
Time Frame	PSA was evaluated at screening, on Day 1 of each cycle, at the end of treatment visit and during off-treatment follow up (up to 27 months)

Outcome Measure Data

Analysis Population Description

Subjects were evaluable for PSA response if they had baseline PSA and at least two post baseline PSA values. One subject was not evaluable for PSA response; he had only one post baseline PSA value. A PSA response was defined in the protocol as a decrease in PSA of ≥ 50% relative to baseline on two or more consecutive measurements 4-6 weeks apart.

Arm/Group Title	OGX-011 / Mitoxantrone/Prednisone	OGX-011 / Docetaxel/Prednisone
Arm/Group Description	All subjects began with oral prednisone (5 mg twice daily)on Day-10. Custirsen (OGX-011) was infused intravenously over 2 hours on Day -7, -5 and-3 of cycle 1 (Pretreatment loading doses). OGX-011 was then infused for 2 hours on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone was infused at a dose of 12 mg/m² over 30 minutes on day 1 of each cycle.	All subjects began with oral prednisone (5 mg twice daily)on Day-10. Custirsen (OGX-011) was infused intravenously over 2 hours on Day -7, -5 and -3 of cycle 1 (Pretreatment loading doses). OGX-011 was then to be infused for 2 hours on Days 1, 8, and 15 of each 21-day cycle. Docetaxel was infused at a dose of 75 mg/m² over 60 minutes on day 1 of each cycle.
Measure Participants	23	45
Number (95% Confidence Interval) [percentage of participants]	17 73.9%	31 67.4%

3. Secondary Outcome

Title	Feasibility of Treatment With OGX-011 in Combination With Either Docetaxel/Prednisone or Mitoxantrone/Prednisone as Second Line Chemotherapy Based on Time to Pain Progression
Description	Time to pain progression was defined as the time (months) from the first dose of OGX-011 to the first documentation of pain or analgesic progression or initiation of palliative radiation therapy. Pain response was defined as either a decrease of at least two points on the 11-point Worst Pain Scale, without an increase in analgesic level, maintained for at least two consecutive measurements approximately three weeks apart -or- a decrease in analgesic level, without an increase in pain score, maintained for at least two consecutive measurements approximately three weeks apart.
Time Frame	Enrollment until pain progression (up to 21 months)

Outcome Measure Data

Analysis Population Description

Subjects were evaluable for pain response if they had a baseline Worst Pain Score ≥ 2 or were on opioid analgesics at baseline.

Arm/Group Title	OGX-011 + Mitoxantrone + Prednisone	OGX-011 + Docetaxel + Prednisone
Arm/Group Description	custirsen (OGX-011) in combination with mitoxantrone and prednisone	custirsen (OGX-011) in combination with docetaxel and prednisone
Measure Participants	18	20
Number (95% Confidence Interval) [months]	5.2	7.2

4. Secondary Outcome

Title	Relationship Between Changes in Serum Clusterin Levels and Change in Serum PSA Levels When OGX-011 in Combination With Either Docetaxel/Prednisone or Mitoxantrone/Prednisone is Administered as Second Line Chemotherapy.
Description	Serum clusterin samples were collected prior to receiving OGX-011 loading dose 1, prior to study treatment on Day 1 of each cycle, and at the end of treatment. PSA was evaluated at screening, on Day 1 of each cycle, at the end of treatment visit, and during off-treatment follow-up. PSA response was defined in the protocol as a decrease in PSA of ≥ 50% relative to baseline on two or more consecutive measurements 4-6 weeks apart.
Time Frame	Enrollment until disease progression (up to 13 months)

Outcome Measure Data

Analysis Population Description

All 69 subjects were included. Data are presented for the 20 subjects who achieved a 50% decline in PSA (6 subjects who received mitoxantrone and prednisone in combination with OGX-011 and 14 subjects who received docetaxel and prednisone in combination with OGX-011)

Arm/Group Title	OGX-011 + Mitoxantrone + Prednisone	OGX-011 + Docetaxel + Prednisone
Arm/Group Description	custirsen (OGX-011) in combination with mitoxantrone and prednisone	custirsen (OGX-011) in combination with docetaxel and prednisone
Measure Participants	23	46
Minimum clusterin level < or = to 45 mcg/mL	22 95.7%	24 52.2%
Minimum clusterin level > 45 mcg/mL	4 17.4%	7 15.2%

Adverse Events

Arm/Group Title	OGX-011 / Mitoxantrone/Prednisone		OGX-011 / Docetaxel/Prednisone
Arm/Group Description	All subjects began with oral prednisone (5 mg twice daily)on Day-10. Custirsen (OGX-011) was infused intravenously over 2 hours on Day -7, -5 and-3 of cycle 1 (Pretreatment loading doses). OGX-011 was then infused for 2 hours on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone was infused at a dose of 12 mg/m² over 30 minutes on day 1 of each cycle.		All subjects began with oral prednisone (5 mg twice daily)on Day-10. Custirsen (OGX-011) was infused intravenously over 2 hours on Day -7, -5 and -3 of cycle 1 (Pretreatment loading doses). OGX-011 was then to be infused for 2 hours on Days 1, 8, and 15 of each 21-day cycle. Docetaxel was infused at a dose of 75 mg/m² over 60 minutes on day 1 of each cycle.
All Cause Mortality
	OGX-011 / Mitoxantrone/Prednisone		OGX-011 / Docetaxel/Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	OGX-011 / Mitoxantrone/Prednisone		OGX-011 / Docetaxel/Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/23 (26.1%)		12/46 (26.1%)
Blood and lymphatic system disorders
Febrile Neutropenia	1/23 (4.3%)		1/46 (2.2%)
Cardiac disorders
Atrial Fibrillation	0/23 (0%)		1/46 (2.2%)
Cardiac Failure	1/23 (4.3%)		0/46 (0%)
Gastrointestinal disorders
Acute Abdomen	0/23 (0%)		1/46 (2.2%)
Gastrointestinal Haemorrhage	0/23 (0%)		1/46 (2.2%)
Nausea	0/23 (0%)		1/46 (2.2%)
Vomiting	0/23 (0%)		1/46 (2.2%)
General disorders
Asthenia	1/23 (4.3%)		1/46 (2.2%)
Death	0/23 (0%)		1/46 (2.2%)
Infections and infestations
Bronchiolitis	0/23 (0%)		1/46 (2.2%)
Klebsiella Sepsis	0/23 (0%)		1/46 (2.2%)
Pneumonia	0/23 (0%)		1/46 (2.2%)
Upper Respiratory Tract Infection	0/23 (0%)		1/46 (2.2%)
Urinary Tract Infection	0/23 (0%)		1/46 (2.2%)
Septic Shock	1/23 (4.3%)		0/46 (0%)
Metabolism and nutrition disorders
Dehydration	1/23 (4.3%)		1/46 (2.2%)
Musculoskeletal and connective tissue disorders
Bone Pain	1/23 (4.3%)		0/46 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to Meninges	0/23 (0%)		1/46 (2.2%)
Prostate Cancer Metastatic	1/23 (4.3%)		0/46 (0%)
Renal and urinary disorders
Haematuria	0/23 (0%)		1/46 (2.2%)
Urinary Retention	0/23 (0%)		1/46 (2.2%)
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	0/23 (0%)		1/46 (2.2%)
Acute Pulmonary Oedema	1/23 (4.3%)		0/46 (0%)
Other (Not Including Serious) Adverse Events
	OGX-011 / Mitoxantrone/Prednisone		OGX-011 / Docetaxel/Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/23 (100%)		46/46 (100%)
Blood and lymphatic system disorders
Anaemia	8/23 (34.8%)		8/46 (17.4%)
Neutropenia	2/23 (8.7%)		4/46 (8.7%)
Cardiac disorders
Atrial Fibrillation	2/23 (8.7%)		1/46 (2.2%)
Eye disorders
Lacrimation Increased	1/23 (4.3%)		8/46 (17.4%)
Gastrointestinal disorders
Nausea	14/23 (60.9%)		23/46 (50%)
Vomiting	10/23 (43.5%)		16/46 (34.8%)
Diarrhoea	5/23 (21.7%)		19/46 (41.3%)
Constipation	4/23 (17.4%)		10/46 (21.7%)
Abdominal Pain	6/23 (26.1%)		3/46 (6.5%)
Stomatitis	2/23 (8.7%)		4/46 (8.7%)
Abdominal Distension	2/23 (8.7%)		2/46 (4.3%)
Dyspepsia	0/23 (0%)		3/46 (6.5%)
Dysphagia	4/23 (17.4%)		0/46 (0%)
General disorders
Fatigue	18/23 (78.3%)		32/46 (69.6%)
Oedema Peripheral	10/23 (43.5%)		21/46 (45.7%)
Chills	10/23 (43.5%)		19/46 (41.3%)
Pyrexia	14/23 (60.9%)		14/46 (30.4%)
Asthenia	3/23 (13%)		7/46 (15.2%)
Chest Pain	3/23 (13%)		0/46 (0%)
Mucosal Inflammation	3/23 (13%)		0/46 (0%)
Pain	4/23 (17.4%)		1/46 (2.2%)
Infections and infestations
Oral Herpes	1/23 (4.3%)		3/46 (6.5%)
Nasopharyngitis	2/23 (8.7%)		2/46 (4.3%)
Injury, poisoning and procedural complications
Contusion	1/23 (4.3%)		6/46 (13%)
Fall	0/23 (0%)		3/46 (6.5%)
Investigations
Weight Decreased	6/23 (26.1%)		8/46 (17.4%)
Aspartate Aminotransferase Increased	2/23 (8.7%)		0/46 (0%)
Metabolism and nutrition disorders
Decreased Appetite	12/23 (52.2%)		16/46 (34.8%)
Dehydration	0/23 (0%)		4/46 (8.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/23 (21.7%)		12/46 (26.1%)
Back Pain	6/23 (26.1%)		10/46 (21.7%)
Bone Pain	7/23 (30.4%)		8/46 (17.4%)
Pain in Extremity	5/23 (21.7%)		6/46 (13%)
Musculoskeletal Pain	3/23 (13%)		5/46 (10.9%)
Muscular Weakness	0/23 (0%)		6/46 (13%)
Myalgia	0/23 (0%)		4/46 (8.7%)
Musculoskeletal Chest Pain	3/23 (13%)		2/46 (4.3%)
Nervous system disorders
Neuropathy Peripheral	3/23 (13%)		13/46 (28.3%)
Dysgeusia	3/23 (13%)		12/46 (26.1%)
Dizziness	3/23 (13%)		11/46 (23.9%)
Headache	7/23 (30.4%)		4/46 (8.7%)
Hypoaesthesia	2/23 (8.7%)		3/46 (6.5%)
Peripheral Sensory Neuropathy	0/23 (0%)		3/46 (6.5%)
Tremor	2/23 (8.7%)		0/46 (0%)
Neuralgia	0/23 (0%)		3/46 (6.5%)
Syncope	0/23 (0%)		3/46 (6.5%)
Psychiatric disorders
Insomnia	8/23 (34.8%)		5/46 (10.9%)
Anxiety	4/23 (17.4%)		6/46 (13%)
Depression	2/23 (8.7%)		4/46 (8.7%)
Confused State	2/23 (8.7%)		1/46 (2.2%)
Mood Altered	2/23 (8.7%)		0/46 (0%)
Renal and urinary disorders
Haematuria	1/23 (4.3%)		3/46 (6.5%)
Pollakiuria	2/23 (8.7%)		1/46 (2.2%)
Nocturia	2/23 (8.7%)		0/46 (0%)
Reproductive system and breast disorders
Pelvic Pain	2/23 (8.7%)		2/46 (4.3%)
Respiratory, thoracic and mediastinal disorders
Cough	6/23 (26.1%)		11/46 (23.9%)
Dyspnoea	8/23 (34.8%)		6/46 (13%)
Oropharyngeal Pain	2/23 (8.7%)		3/46 (6.5%)
Rhinorrhoea	0/23 (0%)		3/46 (6.5%)
Dyspnoea Exertional	0/23 (0%)		3/46 (6.5%)
Nasal Congestion	0/23 (0%)		3/46 (6.5%)
Skin and subcutaneous tissue disorders
Alopecia	0/23 (0%)		9/46 (19.6%)
Nail disorder	0/23 (0%)		5/46 (10.9%)
Hyperhidrosis	0/23 (0%)		4/46 (8.7%)
Pruritus	1/23 (4.3%)		3/46 (6.5%)
Vascular disorders
Hypotension	1/23 (4.3%)		5/46 (10.9%)
Hot Flush	4/23 (17.4%)		1/46 (2.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

All investigators had an agreement with the Canadian Urological Oncology Group (CUOG). The investigators were to provide CUOG with text to be presented or published 45 days prior to the release for review. Results from one institution were not to be presented before the multi-center publication. If there is no multi-center publication within 12 months after the Study completion the Investigator had the right to publish the results.