Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Figitumumab Combined With Pegvisomant For Advanced Solid Tumors

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00976508
First received: September 10, 2009
Last updated: October 23, 2013
Last verified: October 2013
Results First Received: October 23, 2013  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Colorectal Neoplasms
Lung Neoplasms
Breast Neoplasms
Prostatic Neoplasms
Sarcoma
Interventions: Drug: figitumumab
Drug: pegvisomant

  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
Figitumumab 20mg/kg + Pegvisomant 10 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.
Figitumumab 20mg/kg + Pegvisomant 20 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Participant Flow:   Overall Study
    Figitumumab 20mg/kg + Pegvisomant 10 mg     Figitumumab 20mg/kg + Pegvisomant 20 mg  
STARTED     17 [1]   6  
COMPLETED     3 [2]   0  
NOT COMPLETED     14     6  
Death                 7                 1  
Lost to Follow-up                 1                 0  
Withdrawal by Subject                 1                 0  
Disease Progression                 4                 4  
Subject Enrolled in Hospice                 1                 0  
Terminated by the Sponsor                 0                 1  
[1] 18 subjects were enrolled; 17 subjects were treated; 1 subject was not eligible.
[2] These subjects withdrew from last study treatment due to progressive disease.



  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
Figitumumab 20 mg/kg +Pegvisomant 10 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.
Figitumumab 20 mg/kg + Pegvisomant 20 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.
Total Total of all reporting groups

Baseline Measures
    Figitumumab 20 mg/kg +Pegvisomant 10 mg     Figitumumab 20 mg/kg + Pegvisomant 20 mg     Total  
Number of Participants  
[units: participants]
  17     6     23  
Age  
[units: Years]
Mean ± Standard Deviation
  49.5  ± 17.4     32.3  ± 9.8     45.0  ± 17.4  
Gender  
[units: Participants]
     
Female     8     5     13  
Male     9     1     10  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)   [ Time Frame: From Screening to the follow-up visit (90 days after last dose of figitimumab) ]

Measure Type Primary
Measure Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measure Description Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. AEs were graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 (Grade [Gr] 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death). Relatedness to [study drug] was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.
Time Frame From Screening to the follow-up visit (90 days after last dose of figitimumab)  
Safety Issue Yes  

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.
Safety analysis set: all enrolled participants who received at least 1 dose of either of the study medications.

Reporting Groups
  Description
Figitumumab 20mg/kg + Pegvisomant 10 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.
Figitumumab 20mg/kg + Pegvisomant 20 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Measured Values
    Figitumumab 20mg/kg + Pegvisomant 10 mg     Figitumumab 20mg/kg + Pegvisomant 20 mg  
Number of Participants Analyzed  
[units: participants]
  17     6  
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)  
[units: Participants]
   
Number of participants with AEs     17     6  
Number of participants with SAEs     9     4  
Number of participants with Gr 3 or Gr 4 AEs     12     4  
Number of participants with Gr 5 AEs     7     1  

No statistical analysis provided for Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)



2.  Primary:   Number of Participants With Dose Limiting Toxicities (DLT)   [ Time Frame: From Cycle 2, Day 1 to Cycle 3, Day 8; from Cycle 1, Day 15 to end of Cycle 2 ]

Measure Type Primary
Measure Title Number of Participants With Dose Limiting Toxicities (DLT)
Measure Description DLT was defined as any of the following events occurring during DLT period and considered related to study medication: Grade (Gr) 4 neutropenia lasting >=7 days, febrile neutropenia (Gr 3 or 4 neutropenia, fever >=38.5 degrees Celsius, lasting over 24 hours), neutropenic infection (Gr >=3 neutropenia, infection); Gr 3 or 4 thrombocytopenia associated with bleeding or Gr 4 thrombocytopenia >=7 days; Gr 3 or 4 lymphopeniab accompanied by an opportunistic infection; other non-hematologic Grade 4 toxicities or symptomatic Gr 3 toxicities that require medical intervention and 14 days to resolve.
Time Frame From Cycle 2, Day 1 to Cycle 3, Day 8; from Cycle 1, Day 15 to end of Cycle 2  
Safety Issue Yes  

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.
Safety analysis set: all enrolled participants who received at least 1 dose of either of the study medications. N=number of participants remained on treatment throughout the required DLT period and included as analyzed for DLT based on the defined DLT evaluability specifications.

Reporting Groups
  Description
Figitumumab 20 mg/kg + Pegvisomant 10 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.
Figitumumab 20mg/kg + Pegvisomant 20 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Measured Values
    Figitumumab 20 mg/kg + Pegvisomant 10 mg     Figitumumab 20mg/kg + Pegvisomant 20 mg  
Number of Participants Analyzed  
[units: participants]
  6     6  
Number of Participants With Dose Limiting Toxicities (DLT)  
[units: participants]
  1     0  

No statistical analysis provided for Number of Participants With Dose Limiting Toxicities (DLT)



3.  Secondary:   Serum Circulating Insulin-like Growth Factor (IGF-1) Levels   [ Time Frame: Days 1 and 15 of Cycle 1 (Baseline); Day 1 of subsequent cycles starting from Cycle 2 to Cycle 27; end of treatment (21 days after last dose of figitumumab); follow-up visit (90 days after last dose of figitumumab) ]

Measure Type Secondary
Measure Title Serum Circulating Insulin-like Growth Factor (IGF-1) Levels
Measure Description The effect of the combined therapy with figitumumab and pegvisomant on circulating concentrations of total IGF-1 was assessed.
Time Frame Days 1 and 15 of Cycle 1 (Baseline); Day 1 of subsequent cycles starting from Cycle 2 to Cycle 27; end of treatment (21 days after last dose of figitumumab); follow-up visit (90 days after last dose of figitumumab)  
Safety Issue No  

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.
Biomarker analysis set: all enrolled participants who had at least 1 baseline or on-study sample submitted. N=number of participants who were evaluable for IGF-1 Levels at prespecified time points.

Reporting Groups
  Description
Figitumumab 20 mg/kg + Pegvisomant 10 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.
Figitumumab 20mg/kg + Pegvisomant 20 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Measured Values
    Figitumumab 20 mg/kg + Pegvisomant 10 mg     Figitumumab 20mg/kg + Pegvisomant 20 mg  
Number of Participants Analyzed  
[units: participants]
  17     6  
Serum Circulating Insulin-like Growth Factor (IGF-1) Levels  
[units: nanogram/milliliterĀ (ng/mL)]
Mean ± Standard Deviation
   
Baseline/Cycle 1 (n = 16, 6)     150.18  ± 77.06     189.17  ± 59.79  
Cycle 2 (n = 12, 6)     725.72  ± 497.12     498.50  ± 218.28  
Cycle 3 (n = 6, 5)     474.53  ± 418.39     247.40  ± 147.41  
Cycle 4 (n = 5, 3)     542.09  ± 510.84     124.67  ± 83.94  
Cycle 5 (n = 3, 4)     990.40  ± 542.21     248.25  ± 127.43  
Cycle 6 (n = 2, 2)     1369.5  ± 161.93     122.50  ± 137.89  
Cycle 7 (n = 1, 2)     1594.00  ± NA [1]   272.50  ± 105.36  
Cycle 8 (n = 0, 2)     NA  ± NA [2]   501.00  ± 94.75  
Cycle 9 (n = 0, 2)     NA  ± NA [2]   331.00  ± 229.10  
Cycle 10 (n = 0, 2)     NA  ± NA [2]   412.50  ± 185.97  
Cycle 11 (n = 0, 2)     NA  ± NA [2]   426.50  ± 119.50  
Cycle 12 (n = 0, 2)     NA  ± NA [2]   375.50  ± 350.02  
Cycle 13 (n = 0, 2)     NA  ± NA [2]   457.50  ± 36.06  
Cycle 14 (n = 0, 2)     NA  ± NA [2]   420.00  ± 45.25  
Cycle 15 (n = 0, 2)     NA  ± NA [2]   444.50  ± 47.38  
Cycle 16 (n = 0, 2)     NA  ± NA [2]   443.50  ± 23.33  
Cycle 17 (n = 0, 2)     NA  ± NA [2]   426.00  ± 4.24  
Cycle 18 (n = 0, 2)     NA  ± NA [2]   570.50  ± 487.20  
Cycle 19 (n = 0, 1)     NA  ± NA [2]   537.00  ± NA [3]
Cycle 20 (n = 0, 2)     NA  ± NA [2]   458.50  ± 239.71  
Cycle 21 (n = 0, 2)     NA  ± NA [2]   437.00  ± 21.21  
Cycle 22 (n = 0, 1)     NA  ± NA [2]   401.00  ± NA [3]
Cycle 23 (n = 0, 1)     NA  ± NA [2]   481.00  ± NA [3]
Cycle 24 (n = 0, 1)     NA  ± NA [2]   361.00  ± NA [3]
Cycle 25 (n = 0, 1)     NA  ± NA [2]   424.00  ± NA [3]
Cycle 26 (n = 0, 1)     NA  ± NA [2]   366.00  ± NA [3]
Cycle 27 (n = 0, 0)     NA  ± NA [2]   NA  ± NA [2]
Follow-Up (n = 2, 1)     791.50  ± 813.88     1285.00  ± NA [3]
[1] The data was not analyzed since only 1 out of 17 participants were evaluable at this time-point.
[2] The data was not analyzed since no participants were evaluable at this time-point.
[3] The data was not analyzed since only 1 out of 6 participants were evaluable at this time-point.

No statistical analysis provided for Serum Circulating Insulin-like Growth Factor (IGF-1) Levels



4.  Secondary:   Cycle 1: Maximum Observed Plasma Concentration (Cmax) of Figitumumab   [ Time Frame: Cycle 1: Day 1 (within 2 hours before figitumumab infusion), Day 2 (1 hour post figitumumab infusion), Day 8 and Day 15 ]

Measure Type Secondary
Measure Title Cycle 1: Maximum Observed Plasma Concentration (Cmax) of Figitumumab
Measure Description No text entered.
Time Frame Cycle 1: Day 1 (within 2 hours before figitumumab infusion), Day 2 (1 hour post figitumumab infusion), Day 8 and Day 15  
Safety Issue No  

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.
PK samples were not analyzed as the study was terminated prematurely due to lack of operational feasibility and the halt of figitumumab development.

Reporting Groups
  Description
Figitumumab 20 mg/kg + Pegvisomant 10 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.
Figitumumab 20mg/kg + Pegvisomant 20 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Measured Values
    Figitumumab 20 mg/kg + Pegvisomant 10 mg     Figitumumab 20mg/kg + Pegvisomant 20 mg  
Number of Participants Analyzed  
[units: participants]
  0     0  
Cycle 1: Maximum Observed Plasma Concentration (Cmax) of Figitumumab          

No statistical analysis provided for Cycle 1: Maximum Observed Plasma Concentration (Cmax) of Figitumumab



5.  Secondary:   Maximum Observed Plasma Concentration (Cmax) of Figitumumab   [ Time Frame: Cycle 2: Day 1 (within 2 hours before and 1 hour after figitumumab infusion); Cycle 3 to Cycle 17: Day 1 (within 2 hours before figitumumab infusion); end of treatment; 90-day follow-up visit ]

Measure Type Secondary
Measure Title Maximum Observed Plasma Concentration (Cmax) of Figitumumab
Measure Description No text entered.
Time Frame Cycle 2: Day 1 (within 2 hours before and 1 hour after figitumumab infusion); Cycle 3 to Cycle 17: Day 1 (within 2 hours before figitumumab infusion); end of treatment; 90-day follow-up visit  
Safety Issue No  

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.
PK samples were not analyzed as the study was terminated prematurely due to lack of operational feasibility and the halt of figitumumab development.

Reporting Groups
  Description
Figitumumab 20 mg/kg + Pegvisomant 10 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.
Figitumumab 20mg/kg + Pegvisomant 20 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Measured Values
    Figitumumab 20 mg/kg + Pegvisomant 10 mg     Figitumumab 20mg/kg + Pegvisomant 20 mg  
Number of Participants Analyzed  
[units: participants]
  0     0  
Maximum Observed Plasma Concentration (Cmax) of Figitumumab          

No statistical analysis provided for Maximum Observed Plasma Concentration (Cmax) of Figitumumab



6.  Secondary:   Cycle 1: Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab   [ Time Frame: Cycle 1: Day 1 (within 2 hours before figitumumab infusion), Day 2 (1 hour post figitumumab infusion), Day 8 and Day 15 ]

Measure Type Secondary
Measure Title Cycle 1: Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab
Measure Description No text entered.
Time Frame Cycle 1: Day 1 (within 2 hours before figitumumab infusion), Day 2 (1 hour post figitumumab infusion), Day 8 and Day 15  
Safety Issue No  

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.
PK samples were not analyzed as the study was terminated prematurely due to lack of operational feasibility and the halt of figitumumab development.

Reporting Groups
  Description
Figitumumab 20 mg/kg + Pegvisomant 10 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.
Figitumumab 20mg/kg + Pegvisomant 20 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Measured Values
    Figitumumab 20 mg/kg + Pegvisomant 10 mg     Figitumumab 20mg/kg + Pegvisomant 20 mg  
Number of Participants Analyzed  
[units: participants]
  0     0  
Cycle 1: Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab          

No statistical analysis provided for Cycle 1: Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab



7.  Secondary:   Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab   [ Time Frame: Cycle 2: Day 1 (within 2 hours before and 1 hour after figitumumab infusion); Cycle 3 to Cycle 17: Day 1 (within 2 hours before figitumumab infusion); end of treatment; 90-day follow-up visit ]

Measure Type Secondary
Measure Title Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab
Measure Description Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab from Cycle 2 to the end of treatment.
Time Frame Cycle 2: Day 1 (within 2 hours before and 1 hour after figitumumab infusion); Cycle 3 to Cycle 17: Day 1 (within 2 hours before figitumumab infusion); end of treatment; 90-day follow-up visit  
Safety Issue No  

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.
PK samples were not analyzed as the study was terminated prematurely due to lack of operational feasibility and the halt of figitumumab development.

Reporting Groups
  Description
Figitumumab 20 mg/kg + Pegvisomant 10 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.
Figitumumab 20mg/kg + Pegvisomant 20 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Measured Values
    Figitumumab 20 mg/kg + Pegvisomant 10 mg     Figitumumab 20mg/kg + Pegvisomant 20 mg  
Number of Participants Analyzed  
[units: participants]
  0     0  
Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab          

No statistical analysis provided for Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab



8.  Secondary:   Cycle 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Figitumumab   [ Time Frame: Days 1, 2, 8 and 15 of Cycle 1; Day 1 of subsequent cycle starting from Cycle 2 (up to Cycle 17); end of treatment ( 21 days after last dose of figitumumab); follow-up visit (90 days after last dose of figitumumab) ]

Measure Type Secondary
Measure Title Cycle 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Figitumumab
Measure Description Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) of figitumumab in cycle 1.
Time Frame Days 1, 2, 8 and 15 of Cycle 1; Day 1 of subsequent cycle starting from Cycle 2 (up to Cycle 17); end of treatment ( 21 days after last dose of figitumumab); follow-up visit (90 days after last dose of figitumumab)  
Safety Issue No  

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.
PK samples were not analyzed as the study was terminated prematurely due to lack of operational feasibility and the halt of figitumumab development.

Reporting Groups
  Description
Figitumumab 20 mg/kg + Pegvisomant 10 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.
Figitumumab 20 mg/kg + Pegvisomant 20 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles (up to total duration of 27 cycles). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily up to total duration of 27 cycles. Each cycle was of 21 days.

Measured Values
    Figitumumab 20 mg/kg + Pegvisomant 10 mg     Figitumumab 20 mg/kg + Pegvisomant 20 mg  
Number of Participants Analyzed  
[units: participants]
  0     0  
Cycle 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Figitumumab          

No statistical analysis provided for Cycle 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Figitumumab



9.  Secondary:   Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)of Figitumumab   [ Time Frame: Cycle 2: Day 1 (within 2 hours before and 1 hour after figitumumab infusion); Cycle 3 to Cycle 17: Day 1 (within 2 hours before figitumumab infusion); end of treatment; 90-day follow-up visit ]

Measure Type Secondary
Measure Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)of Figitumumab
Measure Description Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)of figitumumab after Cycle 1
Time Frame Cycle 2: Day 1 (within 2 hours before and 1 hour after figitumumab infusion); Cycle 3 to Cycle 17: Day 1 (within 2 hours before figitumumab infusion); end of treatment; 90-day follow-up visit  
Safety Issue No  

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.
PK samples were not analyzed as the study was terminated prematurely due to lack of operational feasibility and the halt of figitumumab development.

Reporting Groups
  Description
Figitumumab 20 mg/kg + Pegvisomant 10 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.
Figitumumab 20mg/kg + Pegvisomant 20 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Measured Values
    Figitumumab 20 mg/kg + Pegvisomant 10 mg     Figitumumab 20mg/kg + Pegvisomant 20 mg  
Number of Participants Analyzed  
[units: participants]
  0     0  
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)of Figitumumab          

No statistical analysis provided for Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)of Figitumumab



10.  Secondary:   Area Under the Trough Concentrations (AUCtrough)   [ Time Frame: Cycle 1: Day 15 (within 2 hours before loading dose), Day 16 (within 2 hours pre-SC dose); Cycle 2: Days 1, 8 and 15 (within 2 hours pre-SC dose); Cycle 3 up to Cycle 17: Day 1 (within 2 hours pre-SC dose); end of treatment; 90-day follow-up visit ]

Measure Type Secondary
Measure Title Area Under the Trough Concentrations (AUCtrough)
Measure Description The trough concentration-time profile (AUCtrough) of pegvisomant was to be analyzed by noncompartmental methods.
Time Frame Cycle 1: Day 15 (within 2 hours before loading dose), Day 16 (within 2 hours pre-SC dose); Cycle 2: Days 1, 8 and 15 (within 2 hours pre-SC dose); Cycle 3 up to Cycle 17: Day 1 (within 2 hours pre-SC dose); end of treatment; 90-day follow-up visit  
Safety Issue No  

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.
PK samples were not analyzed as the study was terminated prematurely due to lack of operational feasibility and the halt of figitumumab development.

Reporting Groups
  Description
Figitumumab 20 mg/kg + Pegvisomant 10 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.
Figitumumab 20mg/kg + Pegvisomant 20 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Measured Values
    Figitumumab 20 mg/kg + Pegvisomant 10 mg     Figitumumab 20mg/kg + Pegvisomant 20 mg  
Number of Participants Analyzed  
[units: participants]
  0     0  
Area Under the Trough Concentrations (AUCtrough)          

No statistical analysis provided for Area Under the Trough Concentrations (AUCtrough)



11.  Secondary:   Mean Change in Glucose Levels Between Fasting and Post Glucose Load   [ Time Frame: Screening; Day 8 of Cycle 1; Day 15 of Cycle 2 ]

Measure Type Secondary
Measure Title Mean Change in Glucose Levels Between Fasting and Post Glucose Load
Measure Description The effect of combining figitumumab with pegvisomant was analyzed to assess whether pegvisomant reverses figitumumab-induced glucose intolerance at various pegvisomant dose levels. The change in glucose load was assessed by Glucose Tolerance Testing (GTT) at baseline (fasting), during Cycle 1 following administration of figitumumab alone (post load), and near the end of Cycle 2 (post load) following combined therapy with figitumumab and pegvisomant.
Time Frame Screening; Day 8 of Cycle 1; Day 15 of Cycle 2  
Safety Issue No  

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.
Glucose tolerance set: All enrolled participants who started treatment and who had at least one baseline or on-study sample submitted. N=number of participants with analyable data for this outcome measure.

Reporting Groups
  Description
Figitumumab 20 mg/kg + Pegvisomant 10 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.
Figitumumab 20mg/kg + Pegvisomant 20 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Measured Values
    Figitumumab 20 mg/kg + Pegvisomant 10 mg     Figitumumab 20mg/kg + Pegvisomant 20 mg  
Number of Participants Analyzed  
[units: participants]
  17     6  
Mean Change in Glucose Levels Between Fasting and Post Glucose Load  
[units: milligram/deciliterĀ (mg/dL)]
Mean ± Standard Deviation
   
Screening (n = 17, 6)     30.35  ± 34.02     4.67  ± 17.60  
Cycle 1 Day 8 (n = 15, 5)     37.68  ± 30.95     15.40  ± 32.04  
Cycle 2 Day 15 (n = 4, 5)     55.15  ± 49.35     13.40  ± 28.35  

No statistical analysis provided for Mean Change in Glucose Levels Between Fasting and Post Glucose Load



12.  Secondary:   Percentage of Participants Reporting Positive Anti-Drug Antibodies (ADA) Response for Figitumumab   [ Time Frame: Day 1 of Cycles 1 and 4; end of treatment (21 days after last dose of figitumumab); follow-up visit (90 days after last dose of figitumumab) ]

Measure Type Secondary
Measure Title Percentage of Participants Reporting Positive Anti-Drug Antibodies (ADA) Response for Figitumumab
Measure Description Percentage of participants with positive total or neutralizing ADA for figitumumab.
Time Frame Day 1 of Cycles 1 and 4; end of treatment (21 days after last dose of figitumumab); follow-up visit (90 days after last dose of figitumumab)  
Safety Issue No  

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.
ADA samples were not analyzed as the study was terminated prematurely due to lack of operational feasibility and the halt of figitumumab development.

Reporting Groups
  Description
Figitumumab 20 mg/kg + Pegvisomant 10 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.
Figitumumab 20mg/kg + Pegvisomant 20 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Measured Values
    Figitumumab 20 mg/kg + Pegvisomant 10 mg     Figitumumab 20mg/kg + Pegvisomant 20 mg  
Number of Participants Analyzed  
[units: participants]
  0     0  
Percentage of Participants Reporting Positive Anti-Drug Antibodies (ADA) Response for Figitumumab          

No statistical analysis provided for Percentage of Participants Reporting Positive Anti-Drug Antibodies (ADA) Response for Figitumumab



13.  Secondary:   Number of Participants With Objective Response   [ Time Frame: From Screening, odd numbered cycles (predose, Cycle 3, 5, 7 etc.) up to Cycle 27 or end of treatment visit (21 days after last dose of figitumumab) ]

Measure Type Secondary
Measure Title Number of Participants With Objective Response
Measure Description Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST)version 1.1. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST version 1.1. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
Time Frame From Screening, odd numbered cycles (predose, Cycle 3, 5, 7 etc.) up to Cycle 27 or end of treatment visit (21 days after last dose of figitumumab)  
Safety Issue No  

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.
Response-evaluable set: All participants who started Cycle 1 with an adequate baseline tumor assessment and at least 1 follow up tumor assessment.

Reporting Groups
  Description
Figitumumab 20 mg/kg + Pegvisomant 10 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.
Figitumumab 20mg/kg + Pegvisomant 20 mg Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Measured Values
    Figitumumab 20 mg/kg + Pegvisomant 10 mg     Figitumumab 20mg/kg + Pegvisomant 20 mg  
Number of Participants Analyzed  
[units: participants]
  17     6  
Number of Participants With Objective Response  
[units: participants]
  0     3  

No statistical analysis provided for Number of Participants With Objective Response




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
The study was terminated prematurely due to lack of operational feasibility and the halt of figitumumab development.


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