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A Safety and Efficacy Study of Intetumumab, Alone and in Combination With Dacarbazine, in Participants With Stage 4 Melanoma

This study has been completed.
Sponsor:
Collaborator:
Janssen-Cilag Farmaceutica, S.R.L.
Information provided by (Responsible Party):
Centocor, Inc.
ClinicalTrials.gov Identifier:
NCT00246012
First received: October 28, 2005
Last updated: July 17, 2013
Last verified: July 2013
Results First Received: May 1, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Melanoma
Interventions: Drug: Intetumumab
Drug: Dacarbazine
Drug: Placebo

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Intetumumab 3 mg/kg [Phase 1 (Part 1)] Intetumumab was administered at the dose of 3 milligram per kilogram (mg/kg) as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over a period of 2 hours (hr) (± 15 minutes) once every 3 weeks until the occurrence of dose limiting toxicities (DLTs). If after an evaluation of the preliminary single-dose pharmacokinetics, receptor saturation was not observed at the 3 mg/kg or 5 mg/kg dose level, that dose of intetumumab was discontinued in Part 1 and participants were treated at the highest, documented safe dose level at which receptor saturation was observed.
Intetumumab 5 mg/kg [Phase 1 (Part 1)] Intetumumab was administered at the dose of 5 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks until the occurrence of DLTs. If after an evaluation of the preliminary single-dose pharmacokinetics, receptor saturation was not observed at the 3 mg/kg or 5 mg/kg dose level, that dose of intetumumab was discontinued in Part 1 and participants were treated at the highest, documented safe dose level at which receptor saturation was observed.
Intetumumab 10 mg/kg [Phase 1 (Part 1)] Intetumumab was administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks until the occurrence of DLTs.
Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] Intetumumab was administered at the dose of 5 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants responded to therapy with stable disease (SD) or better, they were considered eligible to receive up to 8 cycles of extended administrations. Commercially available dacarbazine was administered at the dose of 1000 milligram per meter-square (mg/m^2) intravenously over a period of 60 minutes (± 30 minutes) prior to intetumumab infusion.
Dacarbazine + Intetumumab 10 mg/kg [Phase 1 (Part 2)] Intetumumab was administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants responded to therapy with SD or better, they were considered eligible to receive up to 8 cycles of extended administrations. Commercially available dacarbazine was administered at the dose of 1000 mg/m^2 intravenously over a period of 60 minutes (± 30 minutes) prior to intetumumab infusion.
Dacarbazine + Placebo [Phase 2] Placebo was administered intravenously over a period of 2 hr (±15 minutes). Commercially available dacarbazine was administered at the dose of 1000 mg/m^2 intravenously over a period of 60 minutes (± 30 minutes) prior to placebo infusion. In case participants were unable to tolerate dacarbazine even after 2 dose reductions, they were given the option to continue with 10 mg/kg intetumumab alone.
Intetumumab 5 mg/kg [Phase 2] Intetumumab was administered at the dose of 5 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants responded to therapy with SD or better, they were considered eligible to receive up to 8 cycles of extended administrations.
Intetumumab 10 mg/kg [Phase 2] Intetumumab was administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants responded to therapy with SD or better, they were considered eligible to receive up to 8 cycles of extended administrations.
Dacarbazine + Intetumumab 10 mg/kg [Phase 2] Intetumumab was administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants responded to therapy with SD or better, they were considered eligible to receive up to 8 cycles of extended administrations. Commercially available dacarbazine was administered at the dose of 1000 mg/m^2 intravenously over a period of 60 minutes (± 30 minutes) prior to intetumumab infusion.

Participant Flow:   Overall Study
    Intetumumab 3 mg/kg [Phase 1 (Part 1)]     Intetumumab 5 mg/kg [Phase 1 (Part 1)]     Intetumumab 10 mg/kg [Phase 1 (Part 1)]     Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)]     Dacarbazine + Intetumumab 10 mg/kg [Phase 1 (Part 2)]     Dacarbazine + Placebo [Phase 2]     Intetumumab 5 mg/kg [Phase 2]     Intetumumab 10 mg/kg [Phase 2]     Dacarbazine + Intetumumab 10 mg/kg [Phase 2]  
STARTED     3     3     3     3     3     32     32     33     32  
Treated     3     3     3     3     3     31     31     33     32  
COMPLETED     0     2     1     0     0     4     1     5     4  
NOT COMPLETED     3     1     2     3     3     28     31     28     28  
Adverse Event                 0                 0                 0                 0                 0                 1                 0                 0                 2  
Withdrawal by Subject                 0                 0                 0                 0                 0                 1                 0                 0                 0  
Disease progression                 3                 1                 2                 3                 3                 25                 30                 27                 26  
unspecified                 0                 0                 0                 0                 0                 0                 0                 1                 0  
Randomly assigned but not treated                 0                 0                 0                 0                 0                 1                 1                 0                 0  



  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.
No text entered.

Reporting Groups
  Description
Intetumumab 3 mg/kg [Phase 1 (Part 1)] Intetumumab was administered at the dose of 3 milligram per kilogram (mg/kg) as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) over a period of 2 hours (hr) (± 15 minutes) once every 3 weeks until the occurrence of dose limiting toxicities (DLTs). If after an evaluation of the preliminary single-dose pharmacokinetics, receptor saturation was not observed at the 3 mg/kg or 5 mg/kg dose level, that dose of intetumumab was discontinued in Part 1 and participants were treated at the highest, documented safe dose level at which receptor saturation was observed.
Intetumumab 5 mg/kg [Phase 1 (Part 1)] Intetumumab was administered at the dose of 5 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks until the occurrence of DLTs. If after an evaluation of the preliminary single-dose pharmacokinetics, receptor saturation was not observed at the 3 mg/kg or 5 mg/kg dose level, that dose of intetumumab was discontinued in Part 1 and participants were treated at the highest, documented safe dose level at which receptor saturation was observed.
Intetumumab 10 mg/kg [Phase 1 (Part 1)] Intetumumab was administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks until the occurrence of DLTs.
Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)] Intetumumab was administered at the dose of 5 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants responded to therapy with stable disease (SD) or better, they were considered eligible to receive up to 8 cycles of extended administrations. Commercially available dacarbazine was administered at the dose of 1000 milligram per meter-square (mg/m^2) intravenously over a period of 60 minutes (± 30 minutes) prior to intetumumab infusion.
Dacarbazine + Intetumumab 10 mg/kg [Phase 1 (Part 2)] Intetumumab was administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants responded to therapy with SD or better, they were considered eligible to receive up to 8 cycles of extended administrations. Commercially available dacarbazine was administered at the dose of 1000 mg/m^2 intravenously over a period of 60 minutes (± 30 minutes) prior to intetumumab infusion.
Dacarbazine + Placebo [Phase 2] Placebo was administered intravenously over a period of 2 hr (±15 minutes). Commercially available dacarbazine was administered at the dose of 1000 mg/m^2 intravenously over a period of 60 minutes (± 30 minutes) prior to placebo infusion. In case participants were unable to tolerate dacarbazine even after 2 dose reductions, they were given the option to continue with 10 mg/kg intetumumab alone.
Intetumumab 5 mg/kg [Phase 2] Intetumumab was administered at the dose of 5 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants responded to therapy with SD or better, they were considered eligible to receive up to 8 cycles of extended administrations.
Intetumumab 10 mg/kg [Phase 2] Intetumumab was administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants responded to therapy with SD or better, they were considered eligible to receive up to 8 cycles of extended administrations.
Dacarbazine + Intetumumab 10 mg/kg [Phase 2] Intetumumab was administered at the dose of 10 mg/kg as intravenous infusion over a period of 2 hr (± 15 minutes) once every 3 weeks for 8 cycles until no evidence of disease progression or unacceptable toxicity. If participants responded to therapy with SD or better, they were considered eligible to receive up to 8 cycles of extended administrations. Commercially available dacarbazine was administered at the dose of 1000 mg/m^2 intravenously over a period of 60 minutes (± 30 minutes) prior to intetumumab infusion.
Total Total of all reporting groups

Baseline Measures
    Intetumumab 3 mg/kg [Phase 1 (Part 1)]     Intetumumab 5 mg/kg [Phase 1 (Part 1)]     Intetumumab 10 mg/kg [Phase 1 (Part 1)]     Dacarbazine + Intetumumab 5 mg/kg [Phase 1 (Part 2)]     Dacarbazine + Intetumumab 10 mg/kg [Phase 1 (Part 2)]     Dacarbazine + Placebo [Phase 2]     Intetumumab 5 mg/kg [Phase 2]     Intetumumab 10 mg/kg [Phase 2]     Dacarbazine + Intetumumab 10 mg/kg [Phase 2]     Total  
Number of Participants  
[units: participants]
  3     3     3     3     3     31     31     33     32     142  
Age  
[units: Years]
Mean ± Standard Deviation
  62.0  ± 10.82     46.7  ± 6.66     61.7  ± 11.59     52.7  ± 15.01     66.0  ± 18.73     63.5  ± 14.17     67.3  ± 11.44     61.5  ± 12.39     57.2  ± 11.45     61.8  ± 12.87  
Gender  
[units: Participants]
                   
Female     1     1     1     1     1     13     8     7     14     47  
Male     2     2     2     2     2     18     23     26     18     95  
Region of Enrollment  
[units: Participants]
                   
Germany     0     0     0     0     0     9     12     10     13     44  
United Kingdom     0     0     0     0     0     6     9     4     5     24  
United States     3     3     3     3     3     16     10     19     14     74  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With Dose Limiting Toxicities (DLTs) - Phase 1   [ Time Frame: Up to 21 days post-first infusion from the last treated participant in Phase 1 ]

2.  Primary:   Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 1)   [ Time Frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose ]

3.  Primary:   Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 1)   [ Time Frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose ]

4.  Primary:   Half-life of Intetumumab - Phase 1 (Part 1)   [ Time Frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose ]

5.  Primary:   Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 1)   [ Time Frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose ]

6.  Primary:   Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 1)   [ Time Frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose ]

7.  Primary:   Accumulation Ratio (R) of Intetumumab - Phase 1 (Part 1)   [ Time Frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose ]

8.  Primary:   Progression-Free Survival (PFS) - Phase 2   [ Time Frame: From the date of randomization to date of initial documented progressive disease or death, whichever occured first, as assessed upto 6 months after last dose of study medication ]

9.  Secondary:   Percentage of Participants Who Achieved a Best Overall Tumor Response as Complete Response (CR) or Partial Response (PR) - Phase 2   [ Time Frame: Screening, within 1 week of the end of Cycles 2, 4, 6, 8 (but prior to the next cycle dose), and follow-up (3 and 6 months post-last dose where applicable) ]

10.  Secondary:   Percentage of Participants Who Achieved CR - Phase 2   [ Time Frame: Screening, within 1 week of the end of Cycles 2, 4, 6, 8 (but prior to the next cycle dose), and follow-up (3 and 6 months post-last dose where applicable) ]

11.  Secondary:   Percentage of Participants Who Achieved Stable Disease (SD) - Phase 2   [ Time Frame: Screening, within 1 week of the end of Cycles 2, 4, 6, 8 (but prior to the next cycle dose), and follow-up (3 and 6 months post-last dose where applicable) ]

12.  Secondary:   Overall Survival (OS) - Phase 2   [ Time Frame: Every 3 months until death, until lost to follow-up, until withdrawal of consent, or until the Sponsor ends the study, as assessed up to 6 months post-last dose of study medication ]

13.  Secondary:   Duration of Response - Phase 2   [ Time Frame: From the time of initial documented response (CR or PR) to the first documented sign of progression, assessed up to 6 months post-last dose of study medication ]

14.  Secondary:   Time to Worsening in Eastern Cooperative Oncology Group (ECOG) Performance Status - Phase 2   [ Time Frame: Baseline (within 7 days of first infusion of study medication), Day 1 of all 8 cycles, 3 weeks or 1 week post-last dose, 3 months and 6 months post-last dose of study medication ]

15.  Secondary:   Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 2   [ Time Frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose ]

16.  Secondary:   Change From Baseline in Functional Assessment of Cancer Therapy-Melanoma Subscale (FACT-MS) Score - Phase 2   [ Time Frame: Day 1 (pre-dose) of Cycles 1, 2, 3; and final visit (3 weeks post-last dose of study medication) ]

17.  Secondary:   Change From Baseline in Brief Pain Inventory (BPI) Score - Phase 2   [ Time Frame: Day 1 (pre-dose) of Cycles 1, 2, 3; and final visit (3 weeks post-last dose of study medication) ]

18.  Secondary:   Maximum Observed Serum Concentration (Cmax) of Intetumumab - Phase 1 (Part 2)   [ Time Frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose ]

19.  Secondary:   Area Under the Serum Concentration Versus Time Curve (AUC) of Intetumumab - Phase 1 (Part 2)   [ Time Frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose ]

20.  Secondary:   Half-life of Intetumumab - Phase 1 (Part 2)   [ Time Frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose ]

21.  Secondary:   Total Clearance (CL) of Intetumumab After Intravenous Administration - Phase 1 (Part 2)   [ Time Frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose ]

22.  Secondary:   Volume of Distribution (Vz) of Intetumumab - Phase 1 (Part 2)   [ Time Frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose ]

23.  Secondary:   Accumulation Ratio (R) of Intetumumab - Phase 1 (Part 2)   [ Time Frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose ]

24.  Other Pre-specified:   Area Under the Concentration Versus Time Curve Between Zero to Infinite Time (AUCinf) of Intetumumab - Phase 1 (Part 1)   [ Time Frame: Pre-infusion, post-infusion at 2, 4, 8, 24 hour, Day 8, Day 15, post-last dose (3 weeks or 1 week) and 3 months post-last dose ]

25.  Other Pre-specified:   Percentage of Participants Who Achieved a Best Overall Response as CR, PR, or SD - Phase 2   [ Time Frame: Within 28 days of first infusion of study medication, within 1 week of the end of Cycles 2, 4, 6, 8; 3 months and 6 months post-last dose of study medication ]


  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
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  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 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.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Senior Director
Organization: Centocor, Inc.
phone: 908-927-2116


No publications provided


Responsible Party: Centocor, Inc.
ClinicalTrials.gov Identifier: NCT00246012     History of Changes
Other Study ID Numbers: CR006004, C1034T02, 2004-002130-18
Study First Received: October 28, 2005
Results First Received: May 1, 2013
Last Updated: July 17, 2013
Health Authority: United States: Food and Drug Administration