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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00327340
Recruitment Status : Completed
First Posted : May 18, 2006
Results First Posted : August 29, 2012
Last Update Posted : October 5, 2012
Sponsor:
Information provided by (Responsible Party):
Achieve Life Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Prostate Cancer
Interventions Drug: custirsen (OGX-011)/mitoxantrone
Drug: custirsen (OGX-011)/docetaxel
Enrollment 70
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 Details 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
Hide 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
Reason Not Completed
Withdrawal by Subject             1             5
Physician Decision             1             1
Disease Progression             10             19
Symptomatic Disease             0             2
Adverse Event             3             3
Arm/Group Title OGX-011 / Mitoxantrone/Prednisone OGX-011 / Docetaxel/Prednisone Total
Hide 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 Number of Baseline Participants 23 46 69
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 23 participants 46 participants 69 participants
61
(49 to 81)
64
(48 to 80)
63
(48 to 81)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 46 participants 69 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
23
 100.0%
46
 100.0%
69
 100.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 46 participants 69 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   2.2%
1
   1.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   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%
0
   0.0%
Unknown or Not Reported
2
   8.7%
0
   0.0%
2
   2.9%
Karnofsky Score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 23 participants 46 participants 69 participants
60-70% 2 6 8
80% 7 13 20
90% 7 22 29
100% 7 5 12
[1]
Measure Description:

The Karnofsky Performance Scale Index allows patients to be classified as to their functional impairment.

100%=Normal no complaints; no evidence of disease 90%=Able to carry on normal activity; minor signs or symptoms of disease 80%=Normal activity with effort;some signs or symptoms of disease 60-70%=Able to care for self;unable to do active work

1.Primary Outcome
Title Safety and Tolerability of Custirsen (OGX-011) in Combination With Either Docetaxel/Prednisone or Mitoxantrone/Prednisone as Second-line Chemotherapy.
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
custirsen (OGX-011) in combination with mitoxantrone and prednisone
custirsen (OGX-011) in combination with docetaxel and prednisone
Overall Number of Participants Analyzed 23 46
Measure Type: Number
Unit of Measure: percentage of participants
Percent of Subjects with Serious Adverse Events 26 26
Percent of Subjects with Grade 5 Adverse Events 13 4
Percent of Subjects with Grade 4 Adverse Events 26 15
Percent of Subjects with Grade 3 Adverse Events 70 52
Percent of Subjects with Grade 2 Adverse Events 83 98
Percent of Subjects with Grade 1 Adverse Events 100 100
Percent of Subjects who Discontinued Study Drug 22 17
2.Secondary Outcome
Title Feasibility of Treatment With Custirsen (OGX-011) in Combination With Second-line Chemotherapy Based on Prostate Specific Antigen (PSA) Response
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 23 45
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
17
(5.0 to 38.8)
31
(18.2 to 46.6)
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
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
custirsen (OGX-011) in combination with mitoxantrone and prednisone
custirsen (OGX-011) in combination with docetaxel and prednisone
Overall Number of Participants Analyzed 18 20
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: months
5.2
(1.6 to 8.1)
7.2
(5.8 to 10.6)
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.
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
custirsen (OGX-011) in combination with mitoxantrone and prednisone
custirsen (OGX-011) in combination with docetaxel and prednisone
Overall Number of Participants Analyzed 23 46
Measure Type: Number
Unit of Measure: percentage of participants
Minimum clusterin level < or = to 45 mcg/mL 22 24
Minimum clusterin level > 45 mcg/mL 4 7
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title OGX-011 / Mitoxantrone/Prednisone OGX-011 / Docetaxel/Prednisone
Hide 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 (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
OGX-011 / Mitoxantrone/Prednisone OGX-011 / Docetaxel/Prednisone
Affected / at Risk (%) Affected / at Risk (%)
Total   6/23 (26.09%)   12/46 (26.09%) 
Blood and lymphatic system disorders     
Febrile Neutropenia  1/23 (4.35%)  1/46 (2.17%) 
Cardiac disorders     
Atrial Fibrillation  0/23 (0.00%)  1/46 (2.17%) 
Cardiac Failure  1/23 (4.35%)  0/46 (0.00%) 
Gastrointestinal disorders     
Acute Abdomen  0/23 (0.00%)  1/46 (2.17%) 
Gastrointestinal Haemorrhage  0/23 (0.00%)  1/46 (2.17%) 
Nausea  0/23 (0.00%)  1/46 (2.17%) 
Vomiting  0/23 (0.00%)  1/46 (2.17%) 
General disorders     
Asthenia  1/23 (4.35%)  1/46 (2.17%) 
Death  0/23 (0.00%)  1/46 (2.17%) 
Infections and infestations     
Bronchiolitis  0/23 (0.00%)  1/46 (2.17%) 
Klebsiella Sepsis  0/23 (0.00%)  1/46 (2.17%) 
Pneumonia  0/23 (0.00%)  1/46 (2.17%) 
Upper Respiratory Tract Infection  0/23 (0.00%)  1/46 (2.17%) 
Urinary Tract Infection  0/23 (0.00%)  1/46 (2.17%) 
Septic Shock  1/23 (4.35%)  0/46 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1/23 (4.35%)  1/46 (2.17%) 
Musculoskeletal and connective tissue disorders     
Bone Pain  1/23 (4.35%)  0/46 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Metastases to Meninges  0/23 (0.00%)  1/46 (2.17%) 
Prostate Cancer Metastatic  1/23 (4.35%)  0/46 (0.00%) 
Renal and urinary disorders     
Haematuria  0/23 (0.00%)  1/46 (2.17%) 
Urinary Retention  0/23 (0.00%)  1/46 (2.17%) 
Respiratory, thoracic and mediastinal disorders     
Pleural Effusion  0/23 (0.00%)  1/46 (2.17%) 
Acute Pulmonary Oedema  1/23 (4.35%)  0/46 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
OGX-011 / Mitoxantrone/Prednisone OGX-011 / Docetaxel/Prednisone
Affected / at Risk (%) Affected / at Risk (%)
Total   23/23 (100.00%)   46/46 (100.00%) 
Blood and lymphatic system disorders     
Anaemia  8/23 (34.78%)  8/46 (17.39%) 
Neutropenia  2/23 (8.70%)  4/46 (8.70%) 
Cardiac disorders     
Atrial Fibrillation  2/23 (8.70%)  1/46 (2.17%) 
Eye disorders     
Lacrimation Increased  1/23 (4.35%)  8/46 (17.39%) 
Gastrointestinal disorders     
Nausea  14/23 (60.87%)  23/46 (50.00%) 
Vomiting  10/23 (43.48%)  16/46 (34.78%) 
Diarrhoea  5/23 (21.74%)  19/46 (41.30%) 
Constipation  4/23 (17.39%)  10/46 (21.74%) 
Abdominal Pain  6/23 (26.09%)  3/46 (6.52%) 
Stomatitis  2/23 (8.70%)  4/46 (8.70%) 
Abdominal Distension  2/23 (8.70%)  2/46 (4.35%) 
Dyspepsia  0/23 (0.00%)  3/46 (6.52%) 
Dysphagia  4/23 (17.39%)  0/46 (0.00%) 
General disorders     
Fatigue  18/23 (78.26%)  32/46 (69.57%) 
Oedema Peripheral  10/23 (43.48%)  21/46 (45.65%) 
Chills  10/23 (43.48%)  19/46 (41.30%) 
Pyrexia  14/23 (60.87%)  14/46 (30.43%) 
Asthenia  3/23 (13.04%)  7/46 (15.22%) 
Chest Pain  3/23 (13.04%)  0/46 (0.00%) 
Mucosal Inflammation  3/23 (13.04%)  0/46 (0.00%) 
Pain  4/23 (17.39%)  1/46 (2.17%) 
Infections and infestations     
Oral Herpes  1/23 (4.35%)  3/46 (6.52%) 
Nasopharyngitis  2/23 (8.70%)  2/46 (4.35%) 
Injury, poisoning and procedural complications     
Contusion  1/23 (4.35%)  6/46 (13.04%) 
Fall  0/23 (0.00%)  3/46 (6.52%) 
Investigations     
Weight Decreased  6/23 (26.09%)  8/46 (17.39%) 
Aspartate Aminotransferase Increased  2/23 (8.70%)  0/46 (0.00%) 
Metabolism and nutrition disorders     
Decreased Appetite  12/23 (52.17%)  16/46 (34.78%) 
Dehydration  0/23 (0.00%)  4/46 (8.70%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  5/23 (21.74%)  12/46 (26.09%) 
Back Pain  6/23 (26.09%)  10/46 (21.74%) 
Bone Pain  7/23 (30.43%)  8/46 (17.39%) 
Pain in Extremity  5/23 (21.74%)  6/46 (13.04%) 
Musculoskeletal Pain  3/23 (13.04%)  5/46 (10.87%) 
Muscular Weakness  0/23 (0.00%)  6/46 (13.04%) 
Myalgia  0/23 (0.00%)  4/46 (8.70%) 
Musculoskeletal Chest Pain  3/23 (13.04%)  2/46 (4.35%) 
Nervous system disorders     
Neuropathy Peripheral  3/23 (13.04%)  13/46 (28.26%) 
Dysgeusia  3/23 (13.04%)  12/46 (26.09%) 
Dizziness  3/23 (13.04%)  11/46 (23.91%) 
Headache  7/23 (30.43%)  4/46 (8.70%) 
Hypoaesthesia  2/23 (8.70%)  3/46 (6.52%) 
Peripheral Sensory Neuropathy  0/23 (0.00%)  3/46 (6.52%) 
Tremor  2/23 (8.70%)  0/46 (0.00%) 
Neuralgia  0/23 (0.00%)  3/46 (6.52%) 
Syncope  0/23 (0.00%)  3/46 (6.52%) 
Psychiatric disorders     
Insomnia  8/23 (34.78%)  5/46 (10.87%) 
Anxiety  4/23 (17.39%)  6/46 (13.04%) 
Depression  2/23 (8.70%)  4/46 (8.70%) 
Confused State  2/23 (8.70%)  1/46 (2.17%) 
Mood Altered  2/23 (8.70%)  0/46 (0.00%) 
Renal and urinary disorders     
Haematuria  1/23 (4.35%)  3/46 (6.52%) 
Pollakiuria  2/23 (8.70%)  1/46 (2.17%) 
Nocturia  2/23 (8.70%)  0/46 (0.00%) 
Reproductive system and breast disorders     
Pelvic Pain  2/23 (8.70%)  2/46 (4.35%) 
Respiratory, thoracic and mediastinal disorders     
Cough  6/23 (26.09%)  11/46 (23.91%) 
Dyspnoea  8/23 (34.78%)  6/46 (13.04%) 
Oropharyngeal Pain  2/23 (8.70%)  3/46 (6.52%) 
Rhinorrhoea  0/23 (0.00%)  3/46 (6.52%) 
Dyspnoea Exertional  0/23 (0.00%)  3/46 (6.52%) 
Nasal Congestion  0/23 (0.00%)  3/46 (6.52%) 
Skin and subcutaneous tissue disorders     
Alopecia  0/23 (0.00%)  9/46 (19.57%) 
Nail disorder  0/23 (0.00%)  5/46 (10.87%) 
Hyperhidrosis  0/23 (0.00%)  4/46 (8.70%) 
Pruritus  1/23 (4.35%)  3/46 (6.52%) 
Vascular disorders     
Hypotension  1/23 (4.35%)  5/46 (10.87%) 
Hot Flush  4/23 (17.39%)  1/46 (2.17%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Monica S. Krieger, PhD
Organization: OncoGenex Pharmaceuticals
Phone: 425-686-1558
Responsible Party: Achieve Life Sciences
ClinicalTrials.gov Identifier: NCT00327340     History of Changes
Other Study ID Numbers: OGX-011-07
First Submitted: May 16, 2006
First Posted: May 18, 2006
Results First Submitted: July 26, 2012
Results First Posted: August 29, 2012
Last Update Posted: October 5, 2012