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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00683475
• Collaborator: (none)
• Enrollment: 138
• Locations: 36
• Arms: 2
• Duration (Months): 37
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether IMC-A12 or IMC-1121B (ramucirumab) with Mitoxantrone and Prednisone is effective in the treatment of metastatic androgen- independent prostate cancer (APIC).

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Biological: IMC-A12; Drug: Mitoxantrone; Drug: Prednisone; Biological: IMC-1121B (ramucirumab)	Phase 2

Detailed Description

Prostate cancer is the most frequently diagnosed cancer in men and the second leading cause of cancer-related death in men in the United States. Chemotherapy, either as a single agent or in combination, may lead to clinical response, pain control, and/or improved quality of life. Docetaxel is now the first-line standard therapy for AIPC. Mitoxantrone was approved in 1996 for use in combination with corticosteroids as initial chemotherapy for pain related to advanced Hormone Refractory Prostate Cancer (HRPC). Hormonal manipulations and docetaxel-based chemotherapy are often effective in metastatic prostate cancer; however, disease becomes refractory to these interventions in the majority of men. Although mitoxantrone continues to be a significant agent in the treatment of HRPC, there exists a need for more efficacious therapy in docetaxel-refractory- AIPC. Because of the potential contribution of Insulin Like Growth Factor Receptor (IGF-IR) and VEGFR-2 mediated pathways in prostate cancer pathogenesis, it is hypothesized that each of these biological agents in combination with mitoxantrone and prednisone will result in clinically meaningful activity in AIPC. Therefore, ImClone plans to conduct a randomized Phase 2 trial to assess the safety and efficacy of IMC-A12 or IMC-1121B (ramucirumab) in combination with mitoxantrone and prednisone in participants with AIPC.

Study Design

• Study Type: Interventional
• Actual Enrollment: 138 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Randomized Study of IMC-A12 or IMC-1121B Plus Mitoxantrone and Prednisone in Metastatic Androgen-Independent Prostate Cancer (AIPC) Following Disease Progression on Docetaxel-Based Chemotherapy
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IMC-1121B (ramucirumab) + Mitoxantrone + Prednisone	Drug: Mitoxantrone; Mitoxantrone is to be administered as an I.V. infusion, at 12 milligrams/square meter (mg/m^2) over 5-15 minutes on Day 1 during a 3-week (21-day) cycle. Mitoxantrone treatment is to be continued for a maximum of 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤ 144 mg/m^2) or until there is evidence of disease progression, death, or intolerable toxicity.; Drug: Prednisone; Prednisone (5 mg) is to be self-administered PO BID, each day of the 21-day cycle.; Biological: IMC-1121B (ramucirumab); IMC-1121B (ramucirumab) is to be administered as an intravenous (IV) infusion, 6 milligrams/kilogram (mg/kg) over 1 hour on Days 1, 8, and 15 of each 3-week (21-day) cycle. Ramucirumab treatment is to continue until there is evidence of disease progression, death, intolerable toxicity, or other withdrawal criteria are met.; Other Names: ramucirumab IMC-1121B LY3009806
Experimental: IMC-A12 + Mitoxantrone + Prednisone	Biological: IMC-A12; IMC-A12 is to be administered as an I.V. infusion, 6 mg/kg over 1 hour on Days 1, 8, and 15 of each 3-week (21-day) cycle. IMC-A12 treatment is to continue until there is evidence of disease progression, death, intolerable toxicity, or other withdrawal criteria are met.; Other Names: cixutumumab LY3012217 ; Drug: Mitoxantrone; Mitoxantrone is to be administered as an I.V. infusion, at 12 milligrams/square meter (mg/m^2) over 5-15 minutes on Day 1 during a 3-week (21-day) cycle. Mitoxantrone treatment is to be continued for a maximum of 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤ 144 mg/m^2) or until there is evidence of disease progression, death, or intolerable toxicity.; Drug: Prednisone; Prednisone (5 mg) is to be self-administered PO BID, each day of the 21-day cycle.

Outcome Measures

Primary Outcome Measures

1. Composite Progression-free Survival (cPFS) [Randomization to composite progressive disease, up to 23.4 months]

   Defined as the median time from randomization to the earliest of: Tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST); Evidence of progression by bone scan, performed after completion of the first 3 cycles, demonstrating the appearance of >=2 new lesions; 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) Symptomatic progression (for participants without measurable disease); Other clinical events attributable to prostate cancer that require major interventions; or 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.

Secondary Outcome Measures

1. Summary Listing of Participants Reporting Treatment-Emergent Adverse Events [Randomization to 36.3 months]

   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.

2. Time to Radiographic Evidence of Disease Progression [Randomization to date of radiographic progression, up to 36.3 months]

   Time between date of randomization and earliest date of radiographic progression defined as either: Tumor progression by RECIST; Evidence of progression by bone scan; 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.

3. Prostate Specific Antigen (PSA) Response Rate [Baseline up to data cut-off date (up to 36.3 months)]

   PSA response rate is defined as the percentage of participants with a decrease in PSA >= 50 percent from baseline.

4. Composite Progression-free Survival (cPFS) at 6-months [6 months]

   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.

5. Composite Progression-free Survival (cPFS) at 9-months [9 months]

   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.

6. Composite Progression-free Survival (cPFS) at 12-months [12 months]

   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.

7. Overall Survival (OS) [First dose to death due to any cause up to 36.3 months]

   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.

8. Objective Response Rate (ORR) [Baseline to date of progressive disease or death up to 36.3 months]

   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.

9. Maximum Concentration (Cmax) at Study Day 1 [Day 1]

   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.

10. Maximum Concentration (Cmax) at Study Day 15 [Day 15]

    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.

11. Maximum Concentration (Cmax) at Study Day 16 [Day 16]

    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.

12. Maximum Concentration (Cmax) at Study Day 30 [Day 30]

    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.

13. Minimum Concentration (Cmin) at Study Day 1 [Day 1]

    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.

14. Minimum Concentration (Cmin) at Study Day 15 [Day 15]

    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.

15. Minimum Concentration (Cmin) at Study Day 16 [Day 16]

    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.

16. Minimum Concentration (Cmin) at Study Day 30 [Day 30]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The participant has histologically-confirmed adenocarcinoma of the prostate

• The participant has radiographic evidence of metastatic prostate cancer (stage M1 or D2)

• The participant has prostate cancer unresponsive or refractory to hormone therapy (androgen-independent)

• The participant has had disease progression (clinical or radiographic) while receiving docetaxel, or within 120 days of receiving docetaxel-based chemotherapy and in the opinion of the investigator is unlikely to derive significant benefit from additional docetaxel-based therapy, or was intolerant to therapy with this agent

• The participant must have evidence of progressive disease defined as at least one of the following;

1. Progressive measurable disease: using conventional solid tumor criteria

2. Bone scan progression: at least two new lesions on bone scan

3. Increasing PSA: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2

• The participant has a PSA ≥ 2 ng/mL

• The participant has prior surgical or medical castration with a serum testosterone of <50 ng/mL. If the method of castration is luteinizing hormone releasing level hormone (LHRH) agonists, the participant must be willing to continue the use of LHRH agonists during protocol treatment

• The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2

• The participant has adequate hematologic function (absolute neutrophil count [ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL)

• The participant has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of normal (ULN), Aspartate Transaminase (AST) and Alanine Transaminase (ALT) ≤ 3 times the ULN, or ≤ 5 times the ULN if liver metastases are present)

• The participant has adequate renal function (creatinine ≤ 1.5 x ULN or calculated creatinine clearance > 40 mL/min)

• The participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA). If urine dipstick or routine analysis indicates ≥ 2+ proteinuria, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study

• The participant has adequate coagulation function (an international normalized ratio [INR] ≤ 1.5 and a Partial Thromboplastin Time [PTT] ≤ 5 seconds above the ULN [unless on oral anticoagulant therapy]). Participants receiving full-dose anticoagulation therapy are eligible provided they meet all other criteria, are on a stable dose of oral anticoagulant or low molecular weight heparin (and if on warfarin have a therapeutic INR between 2 and 3)

• The participant has a fasting serum glucose level of < 160 mg/dL, or below the ULN

Exclusion Criteria:

• The participant has received more than one prior cytotoxic chemotherapy regimen for metastatic disease. (Participants who have had a treatment break followed by a second docetaxel-based regimen with subsequent disease progression are eligible.)

• The participant has received prior therapy with mitoxantrone for advanced prostate cancer (prior adjuvant therapy with mitoxantrone is permitted)

• The participant has a history of symptomatic congestive heart failure or has a pre-study echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) that is ≥ 10% below the LLN

• The participant has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or Ramucirumab

• The participant is receiving corticosteroids (dexamethasone, prednisone, or others) at a dose > 5 mg prednisone orally (PO) two times per day (BID) or equivalent. Participants receiving corticosteroids at higher doses may be eligible if their corticosteroid therapy is tapered to study levels (prednisone 5 mg PO BID) prior to first dose of study medication, without concomitant clinical deterioration

• The participant has known or suspected brain or leptomeningeal metastases

• The participant has uncontrolled or poorly controlled hypertension

• The participant has poorly controlled diabetes mellitus. Inclusion Criteria:

• The participant has histologically-confirmed adenocarcinoma of the prostate

• The participant has radiographic evidence of metastatic prostate cancer (stage M1 or D2)

• The participant has prostate cancer unresponsive or refractory to hormone therapy (androgen-independent)

• The participant has had disease progression (clinical or radiographic) while receiving docetaxel, or within 120 days of receiving docetaxel-based chemotherapy and in the opinion of the investigator is unlikely to derive significant benefit from additional docetaxel-based therapy, or was intolerant to therapy with this agent

• The participant must have evidence of progressive disease defined as at least one of the following;

1. Progressive measurable disease: using conventional solid tumor criteria

2. Bone scan progression: at least two new lesions on bone scan

3. Increasing PSA: at least two consecutive rising PSA values over a reference value (PSA #1) taken at least 1 week apart. A third PSA (PSA #3) is required to be greater than PSA #2; if not, a fourth PSA (PSA #4) is required to be greater than PSA #2

• The participant has a PSA ≥ 2 ng/mL

• The participant has prior surgical or medical castration with a serum testosterone of <50 ng/mL. If the method of castration is luteinizing hormone releasing level hormone (LHRH) agonists, the participant must be willing to continue the use of LHRH agonists during protocol treatment

• The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2

• The participant has adequate hematologic function (absolute neutrophil count [ANC]≥1500/uL, hemoglobin ≥9 g/dL, and platelets ≥100,000/uL)

• The participant has adequate hepatic function (bilirubin ≤ 1.5 times the upper limit of normal (ULN), aspartate transaminase [AST] and alanine transaminase [ALT]≤ 3 times the ULN, or ≤ 5 times the ULN if liver metastases are present)

• The participant has adequate renal function (creatinine ≤ 1.5 x ULN or calculated creatinine clearance > 40 mL/min)

• The participant's urinary protein is ≤ 1+ on dipstick or routine urinalysis (UA). If urine dipstick or routine analysis indicates ≥ 2+ proteinuria, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study

• The participant has adequate coagulation function (an international normalized ratio [INR] ≤ 1.5 and a partial thromboplastin time [PTT] ≤ 5 seconds above the ULN [unless on oral anticoagulant therapy]). Participants receiving full-dose anticoagulation therapy are eligible provided they meet all other criteria, are on a stable dose of oral anticoagulant or low molecular weight heparin (and if on warfarin have a therapeutic INR between 2 and 3)

• The participant has a fasting serum glucose level of < 160 mg/dL, or below the ULN

Exclusion Criteria:

• The participant has received more than one prior cytotoxic chemotherapy regimen for metastatic disease. (Participants who have had a treatment break followed by a second docetaxel-based regimen with subsequent disease progression are eligible.)

• The participant has received prior therapy with mitoxantrone for advanced prostate cancer (prior adjuvant therapy with mitoxantrone is permitted)

• The participant has a history of symptomatic congestive heart failure or has a pre-study echocardiogram or multigated acquisition (MUGA) scan with left ventricular ejection fraction (LVEF) that is ≥ 10% below the LLN

• The participant has received radiotherapy ≤ 21 days prior to first dose of IMC-A12 or Ramucirumab

• The participant is receiving corticosteroids (dexamethasone, prednisone, or others) at a dose > 5 mg prednisone orally (PO) two times per day (BID) or equivalent. Participants receiving corticosteroids at higher doses may be eligible if their corticosteroid therapy is tapered to study levels (prednisone 5 mg PO BID) prior to first dose of study medication, without concomitant clinical deterioration

• The participant has known or suspected brain or leptomeningeal metastases

• The participant has uncontrolled or poorly controlled hypertension

• The participant has poorly controlled diabetes mellitus. Participants with a history of diabetes are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition

• The participant has a known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness with a history of diabetes are allowed to participate, provided that their blood glucose is within normal range (fasting < 120 mg/dL or below ULN) and that they are on a stable dietary or therapeutic regimen for this condition

• The participant has a known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ImClone Investigational Site	La Jolla	California	United States	92093
2	ImClone Investigational Site	New Haven	Connecticut	United States	06520
3	ImClone Investigational Site	Boca Raton	Florida	United States	33486
4	ImClone Investigational Site	Port St. Lucie	Florida	United States	34952
5	ImClone Investigational Site	Atlanta	Georgia	United States	30318
6	ImClone Investigational Site	Chicago	Illinois	United States	60611
7	ImClone Investigational Site	Chlcago	Illinois	United States	60637
8	ImClone Investigational Site	Evanston	Illinois	United States	60201
9	ImClone Investigational Site	Maryville	Illinois	United States	62062
10	ImClone Investigational Site	Cedar Rapids	Iowa	United States	52402
11	ImClone Investigational Site	Metairie	Louisiana	United States	70006
12	ImClone Investigational Site	Ann Arbor	Michigan	United States	48109
13	ImClone Investigational Site	Rochester	Minnesota	United States	55905
14	ImClone Investigational Site	St Louis	Missouri	United States	63110
15	ImClone Investigational Site	Billings	Montana	United States	59101
16	ImClone Investigational Site	Roseland	New Jersey	United States	07068
17	ImClone Investigational Site	Buffalo	New York	United States	14263
18	ImClone Investigational Site	East Setauket	New York	United States	11733
19	ImClone Investigational Site	New York	New York	United States	10016
20	ImClone Investigational Site	New York	New York	United States	10019
21	ImClone Investigational Site	New York	New York	United States	10021
22	ImClone Investigational Site	New York	New York	United States	10032
23	ImClone Investigational Site	Durham	North Carolina	United States	27710
24	ImClone Investigational Site	Cleveland	Ohio	United States	44195
25	ImClone Investigational Site	Philadelphia	Pennsylvania	United States	19111
26	ImClone Investigational Site	Pittsburgh	Pennsylvania	United States	15232
27	ImClone Investigational Site	Greenville	South Carolina	United States	29605
28	ImClone Investigational Site	Knoxville	Tennessee	United States	37920
29	ImClone Investigational Site	Nashville	Tennessee	United States	37203
30	ImClone Investigational Site	Abilene	Texas	United States	79606
31	ImClone Investigational Site	Dallas	Texas	United States	75246
32	ImClone Investigational Site	Houston	Texas	United States	77030-4009
33	ImClone Investigational Site	Houston	Texas	United States	77030
34	ImClone Investigational Site	Seattle	Washington	United States	98104
35	ImClone Investigational Site	Seattle	Washington	United States	98109
36	ImClone Investigational Site	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00683475
• Other Study ID Numbers: 13924; CP18-0601; I4T-IE-JVBS
• First Posted: May 23, 2008
• Last Update Posted: Oct 16, 2014
• Last Verified: Oct 1, 2014

• Keywords provided by Eli Lilly and Company: Prostate Cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Prednisone; Mitoxantrone; Ramucirumab; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	IMC-A12 + Mitoxantrone + Prednisone	IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
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

Baseline Characteristics

Arm/Group Title	IMC-A12 + Mitoxantrone + Prednisone	IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone	Total
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 Participants	66	66	132
Age (Count of Participants)
<=18 years	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 (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	66 100%	66 100%	132 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.5%	3 4.5%	4 3%
Not Hispanic or Latino	65 98.5%	63 95.5%	128 97%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
White	61 92.4%	58 87.9%	119 90.2%
Black Or African American	4 6.1%	6 9.1%	10 7.6%
Other	1 1.5%	2 3%	3 2.3%
Region of Enrollment (participants) [Number]
United States	66 100%	66 100%	132 100%

Outcome Measures

1. Primary Outcome

Title	Composite Progression-free Survival (cPFS)
Description	Defined as the median time from randomization to the earliest of: Tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST); Evidence of progression by bone scan, performed after completion of the first 3 cycles, demonstrating the appearance of >=2 new lesions; 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) Symptomatic progression (for participants without measurable disease); Other clinical events attributable to prostate cancer that require major interventions; or 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

Outcome Measure Data

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
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.
Measure Participants	66	66
Median (95% Confidence Interval) [months]	4.1	6.7

2. Secondary Outcome

Title	Summary Listing of Participants Reporting Treatment-Emergent Adverse Events
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

Outcome Measure Data

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
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.
Measure Participants	66	66
A12/1121B Related TEAE	64 97%	63 95.5%
A12/1121B Related Serious TEAE	22 33.3%	16 24.2%
A12/1121B Related Grade >= 3 TEAE	35 53%	31 47%
TEAE Leading to Dose Modification of A12/1121B	35 53%	35 53%
TEAE Leading to Discontinuation of A12/1121B	18 27.3%	25 37.9%

3. Secondary Outcome

Title	Time to Radiographic Evidence of Disease Progression
Description	Time between date of randomization and earliest date of radiographic progression defined as either: Tumor progression by RECIST; Evidence of progression by bone scan; 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

Outcome Measure Data

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
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.
Measure Participants	66	66
Median (95% Confidence Interval) [months]	7.5	10.2

4. Secondary Outcome

Title	Prostate Specific Antigen (PSA) Response Rate
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)

Outcome Measure Data

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
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.
Measure Participants	54	56
Number (95% Confidence Interval) [percentage of participants]	18.5 28%	21.4 32.4%

5. Secondary Outcome

Title	Composite Progression-free Survival (cPFS) at 6-months
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

Outcome Measure Data

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
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.
Measure Participants	66	66
Number (95% Confidence Interval) [percentage of participants]	37.2 56.4%	59.2 89.7%

6. Secondary Outcome

Title	Composite Progression-free Survival (cPFS) at 9-months
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

Outcome Measure Data

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
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.
Measure Participants	66	66
Number (95% Confidence Interval) [percentage of participants]	20.7 31.4%	35.9 54.4%

7. Secondary Outcome

Title	Composite Progression-free Survival (cPFS) at 12-months
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

Outcome Measure Data

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
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.
Measure Participants	66	66
Number (95% Confidence Interval) [percentage of participants]	12.4 18.8%	20.0 30.3%

8. Secondary Outcome

Title	Overall Survival (OS)
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

Outcome Measure Data

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
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.
Measure Participants	66	66
Median (95% Confidence Interval) [months]	10.8	13.0

9. Secondary Outcome

Title	Objective Response Rate (ORR)
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

Outcome Measure Data

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
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.
Measure Participants	46	38
Number (95% Confidence Interval) [percentage of participants]	15.2 23%	31.6 47.9%

10. Secondary Outcome

Title	Maximum Concentration (Cmax) at Study Day 1
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

Analysis Population Description

Zero participants were analyzed.

Arm/Group Title	IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Arm/Group Description	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/m2) 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.
Measure Participants	0

11. Secondary Outcome

Title	Maximum Concentration (Cmax) at Study Day 15
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

Analysis Population Description

Zero participants were analyzed.

Arm/Group Title	IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Arm/Group Description	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/m2) 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.
Measure Participants	0

12. Secondary Outcome

Title	Maximum Concentration (Cmax) at Study Day 16
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

Analysis Population Description

Zero participants were analyzed.

Arm/Group Title	IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Arm/Group Description	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/m2) 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.
Measure Participants	0

13. Secondary Outcome

Title	Maximum Concentration (Cmax) at Study Day 30
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

Analysis Population Description

Zero participants were analyzed.

Arm/Group Title	IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Arm/Group Description	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/m2) 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.
Measure Participants	0

14. Secondary Outcome

Title	Minimum Concentration (Cmin) at Study Day 1
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

Analysis Population Description

Zero participants were analyzed.

Arm/Group Title	IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Arm/Group Description	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/m2) 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.
Measure Participants	0

15. Secondary Outcome

Title	Minimum Concentration (Cmin) at Study Day 15
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

Analysis Population Description

Zero participants were analyzed.

Arm/Group Title	IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Arm/Group Description	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/m2) 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.
Measure Participants	0

16. Secondary Outcome

Title	Minimum Concentration (Cmin) at Study Day 16
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

Analysis Population Description

Zero participants were analyzed.

Arm/Group Title	IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Arm/Group Description	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/m2) 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.
Measure Participants	0

17. Secondary Outcome

Title	Minimum Concentration (Cmin) at Study Day 30
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

Analysis Population Description

Zero participants were analyzed.

Arm/Group Title	IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
Arm/Group Description	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/m2) 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.
Measure Participants	0

Adverse Events

Arm/Group Title	IMC-A12 + Mitoxantrone + Prednisone		IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IMC-A12 + Mitoxantrone + Prednisone		IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/66 (60.6%)		36/66 (54.5%)
Blood and lymphatic system disorders
ANAEMIA	1/66 (1.5%)	1	1/66 (1.5%)	1
DISSEMINATED INTRAVASCULAR COAGULATION	0/66 (0%)	0	1/66 (1.5%)	1
FEBRILE NEUTROPENIA	2/66 (3%)	2	2/66 (3%)	2
LEUKOPENIA	1/66 (1.5%)	1	2/66 (3%)	2
NEUTROPENIA	2/66 (3%)	3	1/66 (1.5%)	1
THROMBOCYTOPENIA	1/66 (1.5%)	4	1/66 (1.5%)	1
Cardiac disorders
ATRIAL FIBRILLATION	0/66 (0%)	0	2/66 (3%)	2
CARDIAC ARREST	1/66 (1.5%)	1	0/66 (0%)	0
CARDIAC FAILURE ACUTE	0/66 (0%)	0	1/66 (1.5%)	1
HYPERTENSIVE CARDIOMYOPATHY	1/66 (1.5%)	1	0/66 (0%)	0
LEFT VENTRICULAR DYSFUNCTION	0/66 (0%)	0	2/66 (3%)	2
MYOCARDIAL INFARCTION	2/66 (3%)	2	0/66 (0%)	0
SICK SINUS SYNDROME	1/66 (1.5%)	1	0/66 (0%)	0
Eye disorders
RETINAL TEAR	0/66 (0%)	0	1/66 (1.5%)	1
Gastrointestinal disorders
ABDOMINAL PAIN	2/66 (3%)	3	1/66 (1.5%)	1
COLITIS	1/66 (1.5%)	1	0/66 (0%)	0
CONSTIPATION	0/66 (0%)	0	1/66 (1.5%)	1
DIARRHOEA	3/66 (4.5%)	3	1/66 (1.5%)	1
GASTROINTESTINAL PERFORATION	1/66 (1.5%)	1	0/66 (0%)	0
NAUSEA	2/66 (3%)	2	2/66 (3%)	3
RECTAL PERFORATION	0/66 (0%)	0	1/66 (1.5%)	1
SMALL INTESTINAL OBSTRUCTION	0/66 (0%)	0	1/66 (1.5%)	2
VOMITING	1/66 (1.5%)	1	2/66 (3%)	3
General disorders
ASTHENIA	2/66 (3%)	2	0/66 (0%)	0
DISEASE PROGRESSION	8/66 (12.1%)	8	2/66 (3%)	2
FATIGUE	2/66 (3%)	2	0/66 (0%)	0
INFUSION RELATED REACTION	0/66 (0%)	0	2/66 (3%)	2
PAIN	1/66 (1.5%)	1	1/66 (1.5%)	1
PYREXIA	2/66 (3%)	3	1/66 (1.5%)	1
Immune system disorders
ANAPHYLACTIC REACTION	0/66 (0%)	0	1/66 (1.5%)	1
Infections and infestations
BACTERAEMIA	1/66 (1.5%)	1	0/66 (0%)	0
CELLULITIS	1/66 (1.5%)	1	0/66 (0%)	0
DIVERTICULITIS	0/66 (0%)	0	1/66 (1.5%)	1
OSTEOMYELITIS	1/66 (1.5%)	1	0/66 (0%)	0
PNEUMONIA	2/66 (3%)	2	1/66 (1.5%)	1
SEPSIS	1/66 (1.5%)	1	1/66 (1.5%)	1
SEPTIC SHOCK	0/66 (0%)	0	1/66 (1.5%)	1
SOFT TISSUE INFECTION	1/66 (1.5%)	1	0/66 (0%)	0
URINARY TRACT INFECTION	0/66 (0%)	0	1/66 (1.5%)	1
UROSEPSIS	0/66 (0%)	0	1/66 (1.5%)	1
WOUND INFECTION	0/66 (0%)	0	1/66 (1.5%)	1
Injury, poisoning and procedural complications
EXPIRED DRUG ADMINISTERED	0/66 (0%)	0	3/66 (4.5%)	3
INCORRECT DOSE ADMINISTERED	1/66 (1.5%)	1	0/66 (0%)	0
MEDICATION ERROR	0/66 (0%)	0	4/66 (6.1%)	4
SPINAL COMPRESSION FRACTURE	0/66 (0%)	0	1/66 (1.5%)	1
Investigations
BLOOD CREATININE INCREASED	1/66 (1.5%)	1	0/66 (0%)	0
Metabolism and nutrition disorders
ANOREXIA	0/66 (0%)	0	1/66 (1.5%)	1
CACHEXIA	1/66 (1.5%)	1	0/66 (0%)	0
DEHYDRATION	4/66 (6.1%)	4	1/66 (1.5%)	1
FAILURE TO THRIVE	1/66 (1.5%)	1	0/66 (0%)	0
HYPERGLYCAEMIA	1/66 (1.5%)	2	1/66 (1.5%)	1
HYPOGLYCAEMIA	0/66 (0%)	0	1/66 (1.5%)	1
HYPOKALAEMIA	1/66 (1.5%)	1	1/66 (1.5%)	1
HYPONATRAEMIA	1/66 (1.5%)	1	0/66 (0%)	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/66 (1.5%)	1	1/66 (1.5%)	1
BACK PAIN	4/66 (6.1%)	4	1/66 (1.5%)	1
BONE PAIN	1/66 (1.5%)	2	0/66 (0%)	0
MUSCULAR WEAKNESS	0/66 (0%)	0	1/66 (1.5%)	1
OSTEONECROSIS	0/66 (0%)	0	1/66 (1.5%)	1
PAIN IN EXTREMITY	0/66 (0%)	0	2/66 (3%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CANCER PAIN	0/66 (0%)	0	1/66 (1.5%)	1
METASTASES TO BONE	0/66 (0%)	0	1/66 (1.5%)	1
METASTASES TO CENTRAL NERVOUS SYSTEM	1/66 (1.5%)	1	0/66 (0%)	0
PROSTATE CANCER	1/66 (1.5%)	1	0/66 (0%)	0
Nervous system disorders
AUTONOMIC NEUROPATHY	1/66 (1.5%)	1	0/66 (0%)	0
CENTRAL NERVOUS SYSTEM MASS	1/66 (1.5%)	1	0/66 (0%)	0
CONVULSION	0/66 (0%)	0	1/66 (1.5%)	1
EMBOLIC STROKE	0/66 (0%)	0	1/66 (1.5%)	1
INTRAVENTRICULAR HAEMORRHAGE	0/66 (0%)	0	1/66 (1.5%)	1
PERIPHERAL MOTOR NEUROPATHY	1/66 (1.5%)	1	0/66 (0%)	0
PRESYNCOPE	1/66 (1.5%)	1	0/66 (0%)	0
SPINAL CORD COMPRESSION	1/66 (1.5%)	1	0/66 (0%)	0
SYNCOPE	3/66 (4.5%)	4	0/66 (0%)	0
TRIGEMINAL NEURALGIA	0/66 (0%)	0	1/66 (1.5%)	1
VASOGENIC CEREBRAL OEDEMA	1/66 (1.5%)	1	0/66 (0%)	0
Psychiatric disorders
MENTAL STATUS CHANGES	0/66 (0%)	0	1/66 (1.5%)	1
Renal and urinary disorders
HAEMATURIA	2/66 (3%)	3	0/66 (0%)	0
HAEMORRHAGE URINARY TRACT	1/66 (1.5%)	1	0/66 (0%)	0
PROTEINURIA	1/66 (1.5%)	1	0/66 (0%)	0
RENAL FAILURE ACUTE	2/66 (3%)	2	1/66 (1.5%)	1
URINARY BLADDER HAEMORRHAGE	1/66 (1.5%)	1	0/66 (0%)	0
URINARY RETENTION	1/66 (1.5%)	1	0/66 (0%)	0
Reproductive system and breast disorders
TESTICULAR PAIN	0/66 (0%)	0	1/66 (1.5%)	1
Respiratory, thoracic and mediastinal disorders
COUGH	0/66 (0%)	0	1/66 (1.5%)	1
DYSPNOEA	0/66 (0%)	0	2/66 (3%)	2
PNEUMONIA ASPIRATION	0/66 (0%)	0	1/66 (1.5%)	1
PULMONARY EMBOLISM	1/66 (1.5%)	1	1/66 (1.5%)	1
RESPIRATORY DISTRESS	2/66 (3%)	2	0/66 (0%)	0
Vascular disorders
DEEP VEIN THROMBOSIS	2/66 (3%)	2	1/66 (1.5%)	1
HYPOTENSION	2/66 (3%)	2	1/66 (1.5%)	1
PELVIC VENOUS THROMBOSIS	0/66 (0%)	0	1/66 (1.5%)	1
VENA CAVA THROMBOSIS	0/66 (0%)	0	1/66 (1.5%)	1
Other (Not Including Serious) Adverse Events
	IMC-A12 + Mitoxantrone + Prednisone		IMC-1121B (Ramucirumab) + Mitoxantrone + Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/66 (98.5%)		66/66 (100%)
Blood and lymphatic system disorders
ANAEMIA	23/66 (34.8%)	42	23/66 (34.8%)	47
LEUKOPENIA	21/66 (31.8%)	36	15/66 (22.7%)	27
LYMPHOPENIA	4/66 (6.1%)	8	1/66 (1.5%)	1
NEUTROPENIA	28/66 (42.4%)	43	24/66 (36.4%)	43
THROMBOCYTOPENIA	12/66 (18.2%)	34	23/66 (34.8%)	51
Eye disorders
LACRIMATION INCREASED	5/66 (7.6%)	7	6/66 (9.1%)	6
Gastrointestinal disorders
ABDOMINAL PAIN	5/66 (7.6%)	6	9/66 (13.6%)	12
ABDOMINAL PAIN UPPER	1/66 (1.5%)	1	4/66 (6.1%)	4
CONSTIPATION	27/66 (40.9%)	38	24/66 (36.4%)	30
DIARRHOEA	29/66 (43.9%)	68	29/66 (43.9%)	55
DRY MOUTH	7/66 (10.6%)	7	8/66 (12.1%)	9
DYSPEPSIA	8/66 (12.1%)	8	7/66 (10.6%)	8
HAEMORRHOIDS	5/66 (7.6%)	5	3/66 (4.5%)	3
NAUSEA	34/66 (51.5%)	55	31/66 (47%)	56
STOMATITIS	7/66 (10.6%)	7	15/66 (22.7%)	18
VOMITING	18/66 (27.3%)	24	19/66 (28.8%)	31
General disorders
ASTHENIA	5/66 (7.6%)	5	12/66 (18.2%)	16
CHILLS	4/66 (6.1%)	5	9/66 (13.6%)	9
FATIGUE	48/66 (72.7%)	130	47/66 (71.2%)	97
MUCOSAL INFLAMMATION	4/66 (6.1%)	5	4/66 (6.1%)	4
OEDEMA PERIPHERAL	10/66 (15.2%)	13	14/66 (21.2%)	21
PYREXIA	10/66 (15.2%)	11	11/66 (16.7%)	12
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION	3/66 (4.5%)	4	10/66 (15.2%)	12
URINARY TRACT INFECTION	8/66 (12.1%)	9	4/66 (6.1%)	7
Injury, poisoning and procedural complications
FALL	4/66 (6.1%)	5	3/66 (4.5%)	3
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED	4/66 (6.1%)	4	7/66 (10.6%)	7
BLOOD CREATININE INCREASED	6/66 (9.1%)	13	2/66 (3%)	5
EJECTION FRACTION DECREASED	6/66 (9.1%)	8	11/66 (16.7%)	13
WEIGHT DECREASED	43/66 (65.2%)	94	40/66 (60.6%)	87
Metabolism and nutrition disorders
ANOREXIA	35/66 (53%)	56	31/66 (47%)	45
DEHYDRATION	15/66 (22.7%)	19	4/66 (6.1%)	4
HYPERGLYCAEMIA	31/66 (47%)	64	8/66 (12.1%)	15
HYPERKALAEMIA	4/66 (6.1%)	10	4/66 (6.1%)	8
HYPOCALCAEMIA	6/66 (9.1%)	7	4/66 (6.1%)	5
HYPOKALAEMIA	4/66 (6.1%)	4	9/66 (13.6%)	21
HYPONATRAEMIA	4/66 (6.1%)	4	0/66 (0%)	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA	16/66 (24.2%)	20	16/66 (24.2%)	29
BACK PAIN	13/66 (19.7%)	18	15/66 (22.7%)	18
BONE PAIN	4/66 (6.1%)	7	4/66 (6.1%)	5
FLANK PAIN	5/66 (7.6%)	5	3/66 (4.5%)	4
GROIN PAIN	3/66 (4.5%)	3	4/66 (6.1%)	4
MUSCLE SPASMS	13/66 (19.7%)	18	4/66 (6.1%)	4
MUSCULAR WEAKNESS	7/66 (10.6%)	8	3/66 (4.5%)	3
MUSCULOSKELETAL CHEST PAIN	5/66 (7.6%)	5	4/66 (6.1%)	4
MUSCULOSKELETAL PAIN	9/66 (13.6%)	13	6/66 (9.1%)	10
MYALGIA	5/66 (7.6%)	6	4/66 (6.1%)	7
PAIN IN EXTREMITY	4/66 (6.1%)	4	10/66 (15.2%)	21
PAIN IN JAW	4/66 (6.1%)	7	2/66 (3%)	5
Nervous system disorders
DIZZINESS	9/66 (13.6%)	13	12/66 (18.2%)	14
DYSGEUSIA	12/66 (18.2%)	18	10/66 (15.2%)	11
HEADACHE	2/66 (3%)	6	13/66 (19.7%)	18
HYPOAESTHESIA	2/66 (3%)	4	4/66 (6.1%)	4
NEUROPATHY PERIPHERAL	2/66 (3%)	6	6/66 (9.1%)	8
PARAESTHESIA	1/66 (1.5%)	1	5/66 (7.6%)	5
Psychiatric disorders
INSOMNIA	5/66 (7.6%)	6	10/66 (15.2%)	11
Renal and urinary disorders
CHROMATURIA	5/66 (7.6%)	5	2/66 (3%)	2
DYSURIA	3/66 (4.5%)	5	4/66 (6.1%)	4
NOCTURIA	11/66 (16.7%)	12	5/66 (7.6%)	5
POLLAKIURIA	2/66 (3%)	2	4/66 (6.1%)	4
PROTEINURIA	3/66 (4.5%)	5	10/66 (15.2%)	32
Respiratory, thoracic and mediastinal disorders
COUGH	13/66 (19.7%)	19	12/66 (18.2%)	13
DYSPHONIA	2/66 (3%)	2	11/66 (16.7%)	14
DYSPNOEA	12/66 (18.2%)	15	21/66 (31.8%)	28
DYSPNOEA EXERTIONAL	3/66 (4.5%)	4	11/66 (16.7%)	12
EPISTAXIS	7/66 (10.6%)	8	13/66 (19.7%)	18
NASAL CONGESTION	1/66 (1.5%)	1	5/66 (7.6%)	5
OROPHARYNGEAL PAIN	4/66 (6.1%)	6	6/66 (9.1%)	9
PARANASAL SINUS HYPERSECRETION	0/66 (0%)	0	4/66 (6.1%)	4
POSTNASAL DRIP	1/66 (1.5%)	1	4/66 (6.1%)	4
Skin and subcutaneous tissue disorders
DRY SKIN	6/66 (9.1%)	6	2/66 (3%)	2
ECCHYMOSIS	10/66 (15.2%)	11	16/66 (24.2%)	19
NAIL DISORDER	9/66 (13.6%)	16	3/66 (4.5%)	3
Vascular disorders
HYPERTENSION	5/66 (7.6%)	5	23/66 (34.8%)	28
HYPOTENSION	8/66 (12.1%)	8	5/66 (7.6%)	5
ORTHOSTATIC HYPOTENSION	4/66 (6.1%)	5	2/66 (3%)	3

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.