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A Study of IMC-A12 or Ramucirumab Plus Mitoxantrone and Prednisone in Prostate Cancer

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ClinicalTrials.gov Identifier: NCT00683475
Recruitment Status : Completed
First Posted : May 23, 2008
Results First Posted : June 18, 2014
Last Update Posted : October 16, 2014
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Prostate Cancer
Interventions Biological: IMC-A12
Drug: Mitoxantrone
Drug: Prednisone
Biological: IMC-1121B (ramucirumab)
Enrollment 138
Recruitment Details  
Pre-assignment Details  
Arm/Group Title IMC-A12 + Mitoxantrone + Prednisone IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Hide Arm/Group Description IMC-A12 intravenous infusion at 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle. IMC-1121B (ramucirumab) intravenous infusion, 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
Period Title: Overall Study
Started 69 69
Received Any Quantity of Study Drug 66 66
Completed 65 66
Not Completed 4 3
Reason Not Completed
Withdrawal by Subject             1             0
Never Treated: Adverse Event             2             3
Never Treated: Progressive Disease             1             0
Arm/Group Title IMC-A12 + Mitoxantrone + Prednisone IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone Total
Hide Arm/Group Description IMC-A12 intravenous infusion at 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle. IMC-1121B (ramucirumab) intravenous infusion, 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle. Total of all reporting groups
Overall Number of Baseline Participants 66 66 132
Hide Baseline Analysis Population Description
Modified intent to treat population (mITT): All participants who received any quantity of study drug.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 66 participants 132 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
30
  45.5%
21
  31.8%
51
  38.6%
>=65 years
36
  54.5%
45
  68.2%
81
  61.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 66 participants 132 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
66
 100.0%
66
 100.0%
132
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 66 participants 132 participants
Hispanic or Latino
1
   1.5%
3
   4.5%
4
   3.0%
Not Hispanic or Latino
65
  98.5%
63
  95.5%
128
  97.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 66 participants 66 participants 132 participants
White 61 58 119
Black Or African American 4 6 10
Other 1 2 3
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 66 participants 66 participants 132 participants
66 66 132
1.Primary Outcome
Title Composite Progression-free Survival (cPFS)
Hide Description

Defined as the median time from randomization to the earliest of:

  1. Tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST);
  2. Evidence of progression by bone scan, performed after completion of the first 3 cycles, demonstrating the appearance of >=2 new lesions;
  3. New skeletal events (New pathologic bone fracture in the region of metastatic disease; New bone lesion requiring radiation or surgery; Spinal cord or nerve root compression)
  4. Symptomatic progression (for participants without measurable disease);
  5. Other clinical events attributable to prostate cancer that require major interventions; or
  6. Death from any cause

Participants who were ongoing with no progression or who discontinued treatment for reasons other than progression were censored at date of last assessment. Participants who started new anticancer treatment before progression were censored at date of last assessment before start of new anti-cancer therapy.

Time Frame Randomization to composite progressive disease, up to 23.4 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Modified intent to treat population (mITT): All participants who received any quantity of study drug.

11 participants were censored in the IMC-A12 + Mitoxantrone + Prednisone arm. 15 participants were censored in the IMC-1121B (ramucirumab) + Mitoxantrone + Prednisone arm.

Arm/Group Title IMC-A12 + Mitoxantrone + Prednisone IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Hide Arm/Group Description:
IMC-A12 intravenous infusion at 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
IMC-1121B (ramucirumab) intravenous infusion, 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
Overall Number of Participants Analyzed 66 66
Median (95% Confidence Interval)
Unit of Measure: months
4.1
(2.2 to 5.6)
6.7
(4.5 to 8.3)
2.Secondary Outcome
Title Summary Listing of Participants Reporting Treatment-Emergent Adverse Events
Hide Description Data presented are the number of participants who experienced A12 or 1121B (ramucirumab) related treatment-emergent adverse events (TEAE), treatment related serious adverse events (SAE), or any Grade 3 or higher TEAE; any TEAE leading to discontinuation of A12 or 1121B (ramucirumab) treatment, and any TEAE leading to dose modification of A12 or 1121B (ramucirumab). A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Event section.
Time Frame Randomization to 36.3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified intent to treat population (mITT): All participants who received any quantity of study drug.
Arm/Group Title IMC-A12 + Mitoxantrone + Prednisone IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Hide Arm/Group Description:
IMC-A12 intravenous infusion at 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
IMC-1121B (ramucirumab) intravenous infusion, 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
Overall Number of Participants Analyzed 66 66
Measure Type: Number
Unit of Measure: participants
A12/1121B Related TEAE 64 63
A12/1121B Related Serious TEAE 22 16
A12/1121B Related Grade >= 3 TEAE 35 31
TEAE Leading to Dose Modification of A12/1121B 35 35
TEAE Leading to Discontinuation of A12/1121B 18 25
3.Secondary Outcome
Title Time to Radiographic Evidence of Disease Progression
Hide Description

Time between date of randomization and earliest date of radiographic progression defined as either:

  1. Tumor progression by RECIST;
  2. Evidence of progression by bone scan;
  3. New skeletal events (New pathologic bone fracture in the region of metastatic disease; New bone lesion requiring radiation or surgery; Spinal cord or nerve root compression).

Participants who were ongoing with no radiographic evidence of disease progression, who discontinued treatment for reasons other than progression,or died before progression were censored at date of last tumor or bone radiographic assessment. Participants who started a new anticancer treatment before progression were censored at date of last tumor or bone radiographic assessment before start of new anti-cancer therapy.

Time Frame Randomization to date of radiographic progression, up to 36.3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Modified intent to treat population (mITT): All participants who received any quantity of study drug.

34 participants were censored in IMC-A12 arm and 34 participants were censored in IMC-1121B (ramucirumab) arm.

Arm/Group Title IMC-A12 + Mitoxantrone + Prednisone IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Hide Arm/Group Description:
IMC-A12 intravenous infusion at 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
IMC-1121B (ramucirumab) intravenous infusion, 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
Overall Number of Participants Analyzed 66 66
Median (95% Confidence Interval)
Unit of Measure: months
7.5
(4.8 to 10.1)
10.2
(7.5 to 12.6)
4.Secondary Outcome
Title Prostate Specific Antigen (PSA) Response Rate
Hide Description PSA response rate is defined as the percentage of participants with a decrease in PSA >= 50 percent from baseline.
Time Frame Baseline up to data cut-off date (up to 36.3 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received any quantity of study drug, had baseline PSA value >= 2 ng/ml and at least one non-missing post-baseline PSA.
Arm/Group Title IMC-A12 + Mitoxantrone + Prednisone IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Hide Arm/Group Description:
IMC-A12 intravenous infusion at 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
IMC-1121B (ramucirumab) intravenous infusion, 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
Overall Number of Participants Analyzed 54 56
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
18.5
(9.3 to 31.4)
21.4
(11.6 to 34.4)
5.Secondary Outcome
Title Composite Progression-free Survival (cPFS) at 6-months
Hide Description

Data presented are the percentage of participants without disease progression at 6 months.

Participants who were ongoing with no progression or who discontinued treatment for reasons other than progression were censored at date of last assessment. Participants who started new anticancer treatment before progression were censored at date of last assessment before start of new anti-cancer therapy.

Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified intent to treat population (mITT): All participants who received any quantity of study drug.
Arm/Group Title IMC-A12 + Mitoxantrone + Prednisone IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Hide Arm/Group Description:
IMC-A12 intravenous infusion at 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
IMC-1121B (ramucirumab) intravenous infusion, 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
Overall Number of Participants Analyzed 66 66
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
37.2
(25.0 to 49.4)
59.2
(45.8 to 70.4)
6.Secondary Outcome
Title Composite Progression-free Survival (cPFS) at 9-months
Hide Description

Data presented are the percentage of participants without disease progression at 9 months.

Participants who were ongoing with no progression or who discontinued treatment for reasons other than progression were censored at date of last assessment. Participants who started new anticancer treatment before progression were censored at date of last assessment before start of new anti-cancer therapy.

Time Frame 9 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified intent to treat population (mITT): All participants who received any quantity of study drug.
Arm/Group Title IMC-A12 + Mitoxantrone + Prednisone IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Hide Arm/Group Description:
IMC-A12 intravenous infusion at 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
IMC-1121B (ramucirumab) intravenous infusion, 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
Overall Number of Participants Analyzed 66 66
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
20.7
(11.2 to 32.1)
35.9
(23.4 to 48.5)
7.Secondary Outcome
Title Composite Progression-free Survival (cPFS) at 12-months
Hide Description

Data presented are the percentage of participants without disease progression at 12 months.

Participants who were ongoing with no progression or who discontinued treatment for reasons other than progression were censored at date of last assessment. Participants who started new anticancer treatment before progression were censored at date of last assessment before start of new anti-cancer therapy.

Time Frame 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified intent to treat population (mITT): All participants who received any quantity of study drug.
Arm/Group Title IMC-A12 + Mitoxantrone + Prednisone IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Hide Arm/Group Description:
IMC-A12 intravenous infusion at 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
IMC-1121B (ramucirumab) intravenous infusion, 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
Overall Number of Participants Analyzed 66 66
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
12.4
(5.2 to 22.9)
20.0
(10.1 to 32.3)
8.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival is defined as the time from randomization to the date of death due to any cause. Participants who were alive at the time of study completion were censored at the time the participant was last known to be alive.
Time Frame First dose to death due to any cause up to 36.3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

Modified intent to treat population (mITT): All participants who received any quantity of study drug.

Nine participants were censored in the IMC-A12 + Mitoxantrone + Prednisone arm. Twelve participants were censored in the IMC-1121B + Mitoxantrone + Prednisone arm

Arm/Group Title IMC-A12 + Mitoxantrone + Prednisone IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Hide Arm/Group Description:
IMC-A12 intravenous infusion at 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
IMC-1121B (ramucirumab) intravenous infusion, 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
Overall Number of Participants Analyzed 66 66
Median (95% Confidence Interval)
Unit of Measure: months
10.8
(6.5 to 13.0)
13.0
(9.5 to 16.0)
9.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description

Objective response is Complete Response (CR) + Partial Response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is a disappearance of all target and non-target lesions; PR is at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions.

Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with measurable disease, multiplied by 100.

Time Frame Baseline to date of progressive disease or death up to 36.3 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants with measurable disease at baseline, who received any quantity of study drug.
Arm/Group Title IMC-A12 + Mitoxantrone + Prednisone IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Hide Arm/Group Description:
IMC-A12 intravenous infusion at 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
IMC-1121B (ramucirumab) intravenous infusion, 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
Overall Number of Participants Analyzed 46 38
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
15.2
(6.3 to 28.9)
31.6
(17.5 to 48.7)
10.Secondary Outcome
Title Maximum Concentration (Cmax) at Study Day 1
Hide Description

Maximum Concentration (Cmax) of Ramucirumab.

All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.

Time Frame Day 1
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Maximum Concentration (Cmax) at Study Day 15
Hide Description

Maximum concentration (Cmax) of Ramucirumab.

All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.

Time Frame Day 15
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Maximum Concentration (Cmax) at Study Day 16
Hide Description

Maximum concentration (Cmax) of Ramucirumab.

All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.

Time Frame Day 16
Outcome Measure Data Not Reported
13.Secondary Outcome
Title Maximum Concentration (Cmax) at Study Day 30
Hide Description

Maximum concentration (Cmax) of Ramucirumab.

All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.

Time Frame Day 30
Outcome Measure Data Not Reported
14.Secondary Outcome
Title Minimum Concentration (Cmin) at Study Day 1
Hide Description

Minimum concentration (Cmin) of Ramucirumab.

All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.

Time Frame Day 1
Outcome Measure Data Not Reported
15.Secondary Outcome
Title Minimum Concentration (Cmin) at Study Day 15
Hide Description

Minimum concentration (Cmin) of Ramucirumab.

All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.

Time Frame Day 15
Outcome Measure Data Not Reported
16.Secondary Outcome
Title Minimum Concentration (Cmin) at Study Day 16
Hide Description

Minimum concentration (Cmin) of Ramucirumab.

All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.

Time Frame Day 16
Outcome Measure Data Not Reported
17.Secondary Outcome
Title Minimum Concentration (Cmin) at Study Day 30
Hide Description

Minimum concentration (Cmin) of Ramucirumab.

All samples were assayed 36 months post sample collection, which exceeds the established long-term serum stability period for ramucirumab. Therefore, concentration data were invalid and pharmacokinetic (PK) analyses could not be conducted.

Time Frame Day 30
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title IMC-A12 + Mitoxantrone + Prednisone IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Hide Arm/Group Description IMC-A12 intravenous infusion at 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle. IMC-1121B (ramucirumab) intravenous infusion, 6 milligrams/kilogram (mg/kg) on Days 1, 8, and 15 of each 21-day cycle. Mitoxantrone intravenous infusion at 12 milligrams/square meter (mg/m^2) on Day 1 of each 21-day cycle. Prednisone at 5 milligrams (mg) is to be self-administered orally, each day of the 21-day cycle.
All-Cause Mortality
IMC-A12 + Mitoxantrone + Prednisone IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
IMC-A12 + Mitoxantrone + Prednisone IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   40/66 (60.61%)      36/66 (54.55%)    
Blood and lymphatic system disorders     
ANAEMIA  1  1/66 (1.52%)  1 1/66 (1.52%)  1
DISSEMINATED INTRAVASCULAR COAGULATION  1  0/66 (0.00%)  0 1/66 (1.52%)  1
FEBRILE NEUTROPENIA  1 [1]  2/66 (3.03%)  2 2/66 (3.03%)  2
LEUKOPENIA  1  1/66 (1.52%)  1 2/66 (3.03%)  2
NEUTROPENIA  1  2/66 (3.03%)  3 1/66 (1.52%)  1
THROMBOCYTOPENIA  1  1/66 (1.52%)  4 1/66 (1.52%)  1
Cardiac disorders     
ATRIAL FIBRILLATION  1  0/66 (0.00%)  0 2/66 (3.03%)  2
CARDIAC ARREST  1  1/66 (1.52%)  1 0/66 (0.00%)  0
CARDIAC FAILURE ACUTE  1  0/66 (0.00%)  0 1/66 (1.52%)  1
HYPERTENSIVE CARDIOMYOPATHY  1  1/66 (1.52%)  1 0/66 (0.00%)  0
LEFT VENTRICULAR DYSFUNCTION  1  0/66 (0.00%)  0 2/66 (3.03%)  2
MYOCARDIAL INFARCTION  1  2/66 (3.03%)  2 0/66 (0.00%)  0
SICK SINUS SYNDROME  1  1/66 (1.52%)  1 0/66 (0.00%)  0
Eye disorders     
RETINAL TEAR  1  0/66 (0.00%)  0 1/66 (1.52%)  1
Gastrointestinal disorders     
ABDOMINAL PAIN  1  2/66 (3.03%)  3 1/66 (1.52%)  1
COLITIS  1  1/66 (1.52%)  1 0/66 (0.00%)  0
CONSTIPATION  1  0/66 (0.00%)  0 1/66 (1.52%)  1
DIARRHOEA  1  3/66 (4.55%)  3 1/66 (1.52%)  1
GASTROINTESTINAL PERFORATION  1  1/66 (1.52%)  1 0/66 (0.00%)  0
NAUSEA  1  2/66 (3.03%)  2 2/66 (3.03%)  3
RECTAL PERFORATION  1  0/66 (0.00%)  0 1/66 (1.52%)  1
SMALL INTESTINAL OBSTRUCTION  1  0/66 (0.00%)  0 1/66 (1.52%)  2
VOMITING  1  1/66 (1.52%)  1 2/66 (3.03%)  3
General disorders     
ASTHENIA  1  2/66 (3.03%)  2 0/66 (0.00%)  0
DISEASE PROGRESSION  1  8/66 (12.12%)  8 2/66 (3.03%)  2
FATIGUE  1  2/66 (3.03%)  2 0/66 (0.00%)  0
INFUSION RELATED REACTION  1  0/66 (0.00%)  0 2/66 (3.03%)  2
PAIN  1  1/66 (1.52%)  1 1/66 (1.52%)  1
PYREXIA  1  2/66 (3.03%)  3 1/66 (1.52%)  1
Immune system disorders     
ANAPHYLACTIC REACTION  1  0/66 (0.00%)  0 1/66 (1.52%)  1
Infections and infestations     
BACTERAEMIA  1  1/66 (1.52%)  1 0/66 (0.00%)  0
CELLULITIS  1  1/66 (1.52%)  1 0/66 (0.00%)  0
DIVERTICULITIS  1  0/66 (0.00%)  0 1/66 (1.52%)  1
OSTEOMYELITIS  1  1/66 (1.52%)  1 0/66 (0.00%)  0
PNEUMONIA  1 [1]  2/66 (3.03%)  2 1/66 (1.52%)  1
SEPSIS  1 [2]  1/66 (1.52%)  1 1/66 (1.52%)  1
SEPTIC SHOCK  1  0/66 (0.00%)  0 1/66 (1.52%)  1
SOFT TISSUE INFECTION  1  1/66 (1.52%)  1 0/66 (0.00%)  0
URINARY TRACT INFECTION  1  0/66 (0.00%)  0 1/66 (1.52%)  1
UROSEPSIS  1  0/66 (0.00%)  0 1/66 (1.52%)  1
WOUND INFECTION  1  0/66 (0.00%)  0 1/66 (1.52%)  1
Injury, poisoning and procedural complications     
EXPIRED DRUG ADMINISTERED  1  0/66 (0.00%)  0 3/66 (4.55%)  3
INCORRECT DOSE ADMINISTERED  1  1/66 (1.52%)  1 0/66 (0.00%)  0
MEDICATION ERROR  1  0/66 (0.00%)  0 4/66 (6.06%)  4
SPINAL COMPRESSION FRACTURE  1  0/66 (0.00%)  0 1/66 (1.52%)  1
Investigations     
BLOOD CREATININE INCREASED  1  1/66 (1.52%)  1 0/66 (0.00%)  0
Metabolism and nutrition disorders     
ANOREXIA  1  0/66 (0.00%)  0 1/66 (1.52%)  1
CACHEXIA  1 [3]  1/66 (1.52%)  1 0/66 (0.00%)  0
DEHYDRATION  1  4/66 (6.06%)  4 1/66 (1.52%)  1
FAILURE TO THRIVE  1  1/66 (1.52%)  1 0/66 (0.00%)  0
HYPERGLYCAEMIA  1  1/66 (1.52%)  2 1/66 (1.52%)  1
HYPOGLYCAEMIA  1  0/66 (0.00%)  0 1/66 (1.52%)  1
HYPOKALAEMIA  1  1/66 (1.52%)  1 1/66 (1.52%)  1
HYPONATRAEMIA  1  1/66 (1.52%)  1 0/66 (0.00%)  0
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  1/66 (1.52%)  1 1/66 (1.52%)  1
BACK PAIN  1  4/66 (6.06%)  4 1/66 (1.52%)  1
BONE PAIN  1  1/66 (1.52%)  2 0/66 (0.00%)  0
MUSCULAR WEAKNESS  1  0/66 (0.00%)  0 1/66 (1.52%)  1
OSTEONECROSIS  1  0/66 (0.00%)  0 1/66 (1.52%)  1
PAIN IN EXTREMITY  1  0/66 (0.00%)  0 2/66 (3.03%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
CANCER PAIN  1  0/66 (0.00%)  0 1/66 (1.52%)  1
METASTASES TO BONE  1  0/66 (0.00%)  0 1/66 (1.52%)  1
METASTASES TO CENTRAL NERVOUS SYSTEM  1  1/66 (1.52%)  1 0/66 (0.00%)  0
PROSTATE CANCER  1  1/66 (1.52%)  1 0/66 (0.00%)  0
Nervous system disorders     
AUTONOMIC NEUROPATHY  1  1/66 (1.52%)  1 0/66 (0.00%)  0
CENTRAL NERVOUS SYSTEM MASS  1  1/66 (1.52%)  1 0/66 (0.00%)  0
CONVULSION  1  0/66 (0.00%)  0 1/66 (1.52%)  1
EMBOLIC STROKE  1  0/66 (0.00%)  0 1/66 (1.52%)  1
INTRAVENTRICULAR HAEMORRHAGE  1 [1]  0/66 (0.00%)  0 1/66 (1.52%)  1
PERIPHERAL MOTOR NEUROPATHY  1  1/66 (1.52%)  1 0/66 (0.00%)  0
PRESYNCOPE  1  1/66 (1.52%)  1 0/66 (0.00%)  0
SPINAL CORD COMPRESSION  1  1/66 (1.52%)  1 0/66 (0.00%)  0
SYNCOPE  1  3/66 (4.55%)  4 0/66 (0.00%)  0
TRIGEMINAL NEURALGIA  1  0/66 (0.00%)  0 1/66 (1.52%)  1
VASOGENIC CEREBRAL OEDEMA  1  1/66 (1.52%)  1 0/66 (0.00%)  0
Psychiatric disorders     
MENTAL STATUS CHANGES  1  0/66 (0.00%)  0 1/66 (1.52%)  1
Renal and urinary disorders     
HAEMATURIA  1  2/66 (3.03%)  3 0/66 (0.00%)  0
HAEMORRHAGE URINARY TRACT  1  1/66 (1.52%)  1 0/66 (0.00%)  0
PROTEINURIA  1  1/66 (1.52%)  1 0/66 (0.00%)  0
RENAL FAILURE ACUTE  1  2/66 (3.03%)  2 1/66 (1.52%)  1
URINARY BLADDER HAEMORRHAGE  1  1/66 (1.52%)  1 0/66 (0.00%)  0
URINARY RETENTION  1  1/66 (1.52%)  1 0/66 (0.00%)  0
Reproductive system and breast disorders     
TESTICULAR PAIN  1  0/66 (0.00%)  0 1/66 (1.52%)  1
Respiratory, thoracic and mediastinal disorders     
COUGH  1  0/66 (0.00%)  0 1/66 (1.52%)  1
DYSPNOEA  1  0/66 (0.00%)  0 2/66 (3.03%)  2
PNEUMONIA ASPIRATION  1  0/66 (0.00%)  0 1/66 (1.52%)  1
PULMONARY EMBOLISM  1  1/66 (1.52%)  1 1/66 (1.52%)  1
RESPIRATORY DISTRESS  1 [4]  2/66 (3.03%)  2 0/66 (0.00%)  0
Vascular disorders     
DEEP VEIN THROMBOSIS  1  2/66 (3.03%)  2 1/66 (1.52%)  1
HYPOTENSION  1  2/66 (3.03%)  2 1/66 (1.52%)  1
PELVIC VENOUS THROMBOSIS  1  0/66 (0.00%)  0 1/66 (1.52%)  1
VENA CAVA THROMBOSIS  1  0/66 (0.00%)  0 1/66 (1.52%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
[1]
Event resulted in one death in IMC-1121B arm
[2]
Event resulted in one death in IMC-A12 arm
[3]
Event resulted in death
[4]
Events resulted in two deaths in IMC-A12 arm
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
IMC-A12 + Mitoxantrone + Prednisone IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   65/66 (98.48%)      66/66 (100.00%)    
Blood and lymphatic system disorders     
ANAEMIA  1  23/66 (34.85%)  42 23/66 (34.85%)  47
LEUKOPENIA  1  21/66 (31.82%)  36 15/66 (22.73%)  27
LYMPHOPENIA  1  4/66 (6.06%)  8 1/66 (1.52%)  1
NEUTROPENIA  1  28/66 (42.42%)  43 24/66 (36.36%)  43
THROMBOCYTOPENIA  1  12/66 (18.18%)  34 23/66 (34.85%)  51
Eye disorders     
LACRIMATION INCREASED  1  5/66 (7.58%)  7 6/66 (9.09%)  6
Gastrointestinal disorders     
ABDOMINAL PAIN  1  5/66 (7.58%)  6 9/66 (13.64%)  12
ABDOMINAL PAIN UPPER  1  1/66 (1.52%)  1 4/66 (6.06%)  4
CONSTIPATION  1  27/66 (40.91%)  38 24/66 (36.36%)  30
DIARRHOEA  1  29/66 (43.94%)  68 29/66 (43.94%)  55
DRY MOUTH  1  7/66 (10.61%)  7 8/66 (12.12%)  9
DYSPEPSIA  1  8/66 (12.12%)  8 7/66 (10.61%)  8
HAEMORRHOIDS  1  5/66 (7.58%)  5 3/66 (4.55%)  3
NAUSEA  1  34/66 (51.52%)  55 31/66 (46.97%)  56
STOMATITIS  1  7/66 (10.61%)  7 15/66 (22.73%)  18
VOMITING  1  18/66 (27.27%)  24 19/66 (28.79%)  31
General disorders     
ASTHENIA  1  5/66 (7.58%)  5 12/66 (18.18%)  16
CHILLS  1  4/66 (6.06%)  5 9/66 (13.64%)  9
FATIGUE  1  48/66 (72.73%)  130 47/66 (71.21%)  97
MUCOSAL INFLAMMATION  1  4/66 (6.06%)  5 4/66 (6.06%)  4
OEDEMA PERIPHERAL  1  10/66 (15.15%)  13 14/66 (21.21%)  21
PYREXIA  1  10/66 (15.15%)  11 11/66 (16.67%)  12
Infections and infestations     
UPPER RESPIRATORY TRACT INFECTION  1  3/66 (4.55%)  4 10/66 (15.15%)  12
URINARY TRACT INFECTION  1  8/66 (12.12%)  9 4/66 (6.06%)  7
Injury, poisoning and procedural complications     
FALL  1  4/66 (6.06%)  5 3/66 (4.55%)  3
Investigations     
ASPARTATE AMINOTRANSFERASE INCREASED  1  4/66 (6.06%)  4 7/66 (10.61%)  7
BLOOD CREATININE INCREASED  1  6/66 (9.09%)  13 2/66 (3.03%)  5
EJECTION FRACTION DECREASED  1  6/66 (9.09%)  8 11/66 (16.67%)  13
WEIGHT DECREASED  1  43/66 (65.15%)  94 40/66 (60.61%)  87
Metabolism and nutrition disorders     
ANOREXIA  1  35/66 (53.03%)  56 31/66 (46.97%)  45
DEHYDRATION  1  15/66 (22.73%)  19 4/66 (6.06%)  4
HYPERGLYCAEMIA  1  31/66 (46.97%)  64 8/66 (12.12%)  15
HYPERKALAEMIA  1  4/66 (6.06%)  10 4/66 (6.06%)  8
HYPOCALCAEMIA  1  6/66 (9.09%)  7 4/66 (6.06%)  5
HYPOKALAEMIA  1  4/66 (6.06%)  4 9/66 (13.64%)  21
HYPONATRAEMIA  1  4/66 (6.06%)  4 0/66 (0.00%)  0
Musculoskeletal and connective tissue disorders     
ARTHRALGIA  1  16/66 (24.24%)  20 16/66 (24.24%)  29
BACK PAIN  1  13/66 (19.70%)  18 15/66 (22.73%)  18
BONE PAIN  1  4/66 (6.06%)  7 4/66 (6.06%)  5
FLANK PAIN  1  5/66 (7.58%)  5 3/66 (4.55%)  4
GROIN PAIN  1  3/66 (4.55%)  3 4/66 (6.06%)  4
MUSCLE SPASMS  1  13/66 (19.70%)  18 4/66 (6.06%)  4
MUSCULAR WEAKNESS  1  7/66 (10.61%)  8 3/66 (4.55%)  3
MUSCULOSKELETAL CHEST PAIN  1  5/66 (7.58%)  5 4/66 (6.06%)  4
MUSCULOSKELETAL PAIN  1  9/66 (13.64%)  13 6/66 (9.09%)  10
MYALGIA  1  5/66 (7.58%)  6 4/66 (6.06%)  7
PAIN IN EXTREMITY  1  4/66 (6.06%)  4 10/66 (15.15%)  21
PAIN IN JAW  1  4/66 (6.06%)  7 2/66 (3.03%)  5
Nervous system disorders     
DIZZINESS  1  9/66 (13.64%)  13 12/66 (18.18%)  14
DYSGEUSIA  1  12/66 (18.18%)  18 10/66 (15.15%)  11
HEADACHE  1  2/66 (3.03%)  6 13/66 (19.70%)  18
HYPOAESTHESIA  1  2/66 (3.03%)  4 4/66 (6.06%)  4
NEUROPATHY PERIPHERAL  1  2/66 (3.03%)  6 6/66 (9.09%)  8
PARAESTHESIA  1  1/66 (1.52%)  1 5/66 (7.58%)  5
Psychiatric disorders     
INSOMNIA  1  5/66 (7.58%)  6 10/66 (15.15%)  11
Renal and urinary disorders     
CHROMATURIA  1  5/66 (7.58%)  5 2/66 (3.03%)  2
DYSURIA  1  3/66 (4.55%)  5 4/66 (6.06%)  4
NOCTURIA  1  11/66 (16.67%)  12 5/66 (7.58%)  5
POLLAKIURIA  1  2/66 (3.03%)  2 4/66 (6.06%)  4
PROTEINURIA  1  3/66 (4.55%)  5 10/66 (15.15%)  32
Respiratory, thoracic and mediastinal disorders     
COUGH  1  13/66 (19.70%)  19 12/66 (18.18%)  13
DYSPHONIA  1  2/66 (3.03%)  2 11/66 (16.67%)  14
DYSPNOEA  1  12/66 (18.18%)  15 21/66 (31.82%)  28
DYSPNOEA EXERTIONAL  1  3/66 (4.55%)  4 11/66 (16.67%)  12
EPISTAXIS  1  7/66 (10.61%)  8 13/66 (19.70%)  18
NASAL CONGESTION  1  1/66 (1.52%)  1 5/66 (7.58%)  5
OROPHARYNGEAL PAIN  1  4/66 (6.06%)  6 6/66 (9.09%)  9
PARANASAL SINUS HYPERSECRETION  1  0/66 (0.00%)  0 4/66 (6.06%)  4
POSTNASAL DRIP  1  1/66 (1.52%)  1 4/66 (6.06%)  4
Skin and subcutaneous tissue disorders     
DRY SKIN  1  6/66 (9.09%)  6 2/66 (3.03%)  2
ECCHYMOSIS  1  10/66 (15.15%)  11 16/66 (24.24%)  19
NAIL DISORDER  1  9/66 (13.64%)  16 3/66 (4.55%)  3
Vascular disorders     
HYPERTENSION  1  5/66 (7.58%)  5 23/66 (34.85%)  28
HYPOTENSION  1  8/66 (12.12%)  8 5/66 (7.58%)  5
ORTHOSTATIC HYPOTENSION  1  4/66 (6.06%)  5 2/66 (3.03%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
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.
Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.
Results Point of Contact
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00683475     History of Changes
Other Study ID Numbers: 13924
CP18-0601 ( Other Identifier: ImClone Systems )
I4T-IE-JVBS ( Other Identifier: Eli Lilly and Company )
First Submitted: May 19, 2008
First Posted: May 23, 2008
Results First Submitted: May 16, 2014
Results First Posted: June 18, 2014
Last Update Posted: October 16, 2014