Study of MDX-010 in Patients With Metastatic Hormone-Refractory Prostate Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00323882
First received: May 8, 2006
Last updated: August 14, 2014
Last verified: August 2014
Results First Received: July 23, 2014  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Prostate Cancer
Neoplasm Metastasis
Intervention: Drug: MDX-010

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Study initiated January 2006; Primary endpoint last visit September 2009; follow up period last visit July 2013 with data cut off September 2013. Male patients with castrate-resistant prostate cancer (CRPC) who met study criteria were enrolled.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
75 participants enrolled and were assigned to treatment; 71 were treated. Reasons for the 4 participants not receiving treatment were not specified by the investigators. Ipilimumab was administered at escalating dosage levels of 3, 5, and 10 mg/kg/dose.

Reporting Groups
  Description
Ipilimumab Monotherapy 3 mg/kg A single dose of 3 mg/kg ipilimumab was administered over 90 minutes intravenously (IV) on Days 1, 22, 43, and 64 for a total of 4 doses in the induction period. Those participants with a clinical response of stable disease (SD) or conflicting disease response assessment (CDRA) at the end of the induction period could have received additional treatment up to a total of 16 doses in the maintenance period. The length of time on study for an individual could be up to 2 years. Follow up for survival status was for up to 5 years after enrollment.
Ipilimumab Monotherapy 5 mg/kg A single dose of 5 mg/kg ipilimumab was administered over 90 minutes IV on Days 1, 22, 43, and 64 for a total of 4 doses (induction). Those participants with a clinical response of SD or CDRA at the end of induction could have received additional treatment up to a total of 16 doses (maintenance). The length of time on study for an individual could be up to 2 years. Follow up for survival status was for up to 5 years after enrollment.
Ipilimumab Monotherapy 10 mg/kg A single dose of 10 mg/kg ipilimumab was administered over 90 minutes IV on Days 1, 22, 43, and 64 for a total of 4 doses in the induction period. Those participants with a clinical response of SD or CDRA at the end of induction could have received additional treatment up to a total of 16 doses in the maintenance period. The length of time on study for an individual could be up to 2 years. Follow up for survival status was for up to 5 years after enrollment.
Ipilimumab 3 mg/kg + XRT Combination Therapy A single dose of 3 mg/kg ipilimumab was administered over 90 minutes IV on Days 1, 22, 43, and 64 for a total of 4 doses in the induction period. In addition, participants received a single dose of 800 rads (8 Gray) of focal radiotherapy (XRT) to each target lesion within 48 hours before the first infusion of ipilimumab during the induction period. According to Response Evaluation Criteria in Solid Tumors (RECIST), target or measurable lesions were defined as lesions that could be accurately measured in at least one dimension (longest diameter recorded) as ≥ 10 mm with spiral computed tomography (CT). Those participants with a clinical response of SD or CDRA at the end of induction could have received additional treatment up to a total 16 doses in the maintenance period. Radiotherapy was not administered during maintenance period. The length of time on study for an individual could be up to 2 years. Follow up for survival status was for up to 5 years after enrollment.
Ipilimumab 10 mg/kg + XRT Combination A single dose of 10 mg/kg ipilimumab was administered over 90 minutes IV on Days 1, 22, 43, and 64 for a total of 4 doses in the induction period. In addition, participants received a single dose of 800 rads (8 Gray) of focal XRT to each target lesion within 48 hours before the first infusion of ipilimumab in the induction period. According to RECIST, target or measurable lesions were defined as lesions that could be accurately measured in at least one dimension (longest diameter recorded) as ≥ 10 mm with spiral CT. Those participants with a clinical response of SD or CDRA at the end of induction period could have received additional treatment up to a total of 16 doses in the maintenance period. Radiotherapy was not administered during maintenance period. The length of time on study for an individual could be up to 2 years. Follow up for survival status was for up to 5 years after enrollment.

Participant Flow:   Overall Study
    Ipilimumab Monotherapy 3 mg/kg     Ipilimumab Monotherapy 5 mg/kg     Ipilimumab Monotherapy 10 mg/kg     Ipilimumab 3 mg/kg + XRT Combination Therapy     Ipilimumab 10 mg/kg + XRT Combination  
STARTED     8     6     16     7     34  
COMPLETED     0     0     3     0     2  
NOT COMPLETED     8     6     13     7     32  
Adverse Event                 2                 1                 1                 1                 3  
Disease Progression                 6                 4                 10                 5                 22  
Death                 0                 1                 1                 0                 5  
Lost to Follow-up                 0                 0                 1                 0                 1  
Not Specified                 0                 0                 0                 1                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants who received at least one dose of study therapy.

Reporting Groups
  Description
Ipilimumab Monotherapy 3 mg/kg A single dose of 3 mg/kg ipilimumab was administered over 90 minutes intravenously (IV) on Days 1, 22, 43, and 64 for a total of 4 doses in the induction period. Those participants with a clinical response of stable disease (SD) or conflicting disease response assessment (CDRA) at the end of induction period could have received additional treatment up to a total of 16 doses in the maintenance period. The length of time on study for an individual could be up to 2 years. Follow up for survival status was for up to 5 years after enrollment.
Ipilimumab Monotherapy 5 mg/kg A single dose of 5 mg/kg ipilimumab was administered over 90 minutes IV on Days 1, 22, 43, and 64 for a total of 4 doses (induction). Those participants with a clinical response of SD or CDRA at the end of induction could have received additional treatment up to a total of 16 doses in the maintenance period. The length of time on study for an individual could be up to 2 years. Follow up for survival status was for up to 5 years after enrollment.
Ipilimumab Monotherapy 10 mg/kg A single dose of 10 mg/kg ipilimumab was administered over 90 minutes IV on Days 1, 22, 43, and 64 for a total of 4 doses in the induction period. Those participants with a clinical response of SD or CDRA at the end of induction could have received additional treatment up to a total of 16 doses in the maintenance period. The length of time on study for an individual could be up to 2 years. Follow up for survival status was for up to 5 years after enrollment.
Ipilimumab 3 mg/kg + XRT Combination Therapy A single dose of 3 mg/kg ipilimumab was administered over 90 minutes IV on Days 1, 22, 43, and 64 for a total of 4 doses in the induction period. In addition, participants received a single dose of 800 rads (8 Gray) of focal radiotherapy (XRT) to each target lesion within 48 hours before the first infusion of ipilimumab during the induction period. According to RECIST, target or measurable lesions were defined as lesions that could be accurately measured in at least one dimension (longest diameter recorded) as ≥ 10 mm with spiral computed tomography (CT). Those participants with a clinical response of SD or CDRA at the end of induction could have received additional treatment up to a total 16 doses in the maintenance period. Radiotherapy was not administered during maintenance period. The length of time on study for an individual could be up to 2 years. Follow up for survival status was for up to 5 years after enrollment.
Ipilimumab 10 mg/kg + XRT Combination A single dose of 10 mg/kg ipilimumab was administered over 90 minutes IV on Days 1, 22, 43, and 64 for a total of 4 doses in the induction period. In addition, participants received a single dose of 800 rads (8 Gray) of focal XRT to each target lesion within 48 hours before the first infusion of ipilimumab in the induction period. According to RECIST, target or measurable lesions were defined as lesions that could be accurately measured in at least one dimension (longest diameter recorded) as ≥ 10 mm with spiral CT. Those participants with a clinical response of SD or CDRA at the end of induction period could have received additional treatment up to a total of 16 doses in the maintenance period. Radiotherapy was not administered during maintenance period. The length of time on study for an individual could be up to 2 years. Follow up for survival status was for up to 5 years after enrollment.
Total Total of all reporting groups

Baseline Measures
    Ipilimumab Monotherapy 3 mg/kg     Ipilimumab Monotherapy 5 mg/kg     Ipilimumab Monotherapy 10 mg/kg     Ipilimumab 3 mg/kg + XRT Combination Therapy     Ipilimumab 10 mg/kg + XRT Combination     Total  
Number of Participants  
[units: participants]
  8     6     16     7     34     71  
Age  
[units: years]
Mean ± Standard Deviation
  68.0  ± 8.1     58.2  ± 5.6     65.2  ± 7.7     67.6  ± 8.5     65.7  ± 9.1     65.4  ± 8.5  
Gender  
[units: participants]
           
Female     0     0     0     0     0     0  
Male     8     6     16     7     34     71  
Race/Ethnicity, Customized  
[units: participants]
           
Asian     0     0     0     0     1     1  
Black     0     0     0     1     3     4  
White     8     6     16     6     30     66  
Region of Enrollment  
[units: participants]
           
United States     8     6     16     7     34     71  
Mean Prostate-Specific Antigen (PSA) in ng/mL [1]
[units: ng/mL]
Mean ± Standard Deviation
  121.6  ± 140.2     48.8  ± 43.9     302.7  ± 521.2     66.6  ± 68.1     250.1  ± 324.1     212.9  ± 346.5  
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) [2]
[units: participants]
           
ECOG PS 0     5     5     10     4     9     33  
ECOG PS 1     3     1     6     2     22     34  
ECOG PS 2     0     0     0     1     0     1  
ECOG PS Not Reported     0     0     0     0     3     3  
[1] PSA is measured in nanograms per milliliter (ng/mL).
[2] ECOG performance: 0= Fully active, able to carry on all pre-disease performance without restriction;1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2=Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=Completely disabled. Cannot carry on any self-care. Totally confined to bed or Chair; 5=Dead



  Outcome Measures
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1.  Primary:   Number of Participants With Serious AEs (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs - Treated Participants   [ Time Frame: Day 1 to last day of study treatment (+70 days) up to 2 years ]

2.  Primary:   Number of Participants With Best PSA Response at Day 85 by Category - PSA Evaluable Participants   [ Time Frame: Day 85 ]

3.  Secondary:   Number of Participants With Best Overall PSA Response by Category - PSA Evaluable Participants   [ Time Frame: Day 1 to last day of study treatment (+70 days) up to 2 years ]

4.  Secondary:   Number of Participants With Best Overall Tumor Response by Category - Tumor Evaluable Participants   [ Time Frame: Day 1 to last day of study treatment (+70 days) up to 2 years ]

5.  Secondary:   Time to PSA Response at Day 85 in Participants With Complete Response (CR) or Confirmed Partial Response (PR) at Day 85   [ Time Frame: Day 1 to Day 85 ]

6.  Secondary:   Overall Tumor Response Rate in 10 mg/kg Ipilimumab Monotherapy and Ipilimumab/XRT Combination Therapy   [ Time Frame: Day 1 to last day of study treatment (+70 days) up to 2 years ]

7.  Secondary:   PSA Response Rate at Day 85 and Overall PSA Response Rate in 10 mg/kg Monotherapy and Combination Therapy   [ Time Frame: Day 85, Day 1 to last day of study treatment (+70 days) up to 2 years ]

8.  Secondary:   Number of Participants Who Died by Date of Primary Analysis and by Date of Completion of Follow Up - All Treated Participants   [ Time Frame: Day 1 to 5 years post treatment ]

9.  Secondary:   Overall Survival at Completion of Follow Up Period - Treated Participants   [ Time Frame: Day 1 to 5 years post treatment ]

10.  Secondary:   Number of Participants With On-Study Hematology Laboratory Tests Worst Common Terminology Criteria (CTC) Grade - Treated Participants   [ Time Frame: Day 1 to last day of study treatment (+70 days) up to 2 years ]

11.  Secondary:   Number of Participants With On-Study Serum Chemistry Laboratory Tests Worst Common Terminology Criteria (CTC) Grade - Treated Participants   [ Time Frame: Day 1 to last day of study treatment (+70 days) up to 2 years ]

12.  Secondary:   Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities at Baseline and During Treatment Period - Treated Participants   [ Time Frame: Baseline up to 2 years ]

13.  Secondary:   Number of Participants Positive for Human Anti-Human Antibodies (HAHA) - Treated Participants   [ Time Frame: Day 1 up to 2 years ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Due to the small number of participants who underwent more than 4 doses of treatment (induction period) and the exploratory nature of this study, not all of the secondary objectives were completed.


  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com


No publications provided by Bristol-Myers Squibb

Publications automatically indexed to this study:

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00323882     History of Changes
Other Study ID Numbers: CA184-017 ST, CA184-017
Study First Received: May 8, 2006
Results First Received: July 23, 2014
Last Updated: August 14, 2014
Health Authority: United States: Food and Drug Administration