A Study of IMC-1121B (Ramucirumab) With or Without Dacarbazine in Metastatic Malignant Melanoma

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00533702
• Collaborator: (none)
• Enrollment: 106
• Locations: 17
• Arms: 2
• Duration (Months): 42
• Patients Per Site: 6.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of this study is to determine the progression-free survival (PFS) of participants with previously untreated metastatic malignant melanoma when treated with IMC-1121B (ramucirumab) alone or in combination with dacarbazine.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Malignant Melanoma	Biological: IMC-1121B (ramucirumab); Drug: Dacarbazine	Phase 2

Detailed Description

The purpose of this study is to determine the antitumor activity and safety profile of IMC-1121B (ramucirumab) when used alone or in combination with dacarbazine in participants with metastatic melanoma who have not received prior chemotherapy for this disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 106 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Randomized, Open-Label Study of IMC-1121B With or Without Dacarbazine in Patients With Metastatic Malignant Melanoma
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IMC-1121B (ramucirumab) IMC-1121B (ramucirumab)	Biological: IMC-1121B (ramucirumab); 10 milligrams/kilogram (mg/kg) intravenously every 3 weeks in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.; Other Names: ramucirumab LY3009806
Active Comparator: IMC-1121B (ramucirumab) + dacarbazine IMC-1121B (ramucirumab) + dacarbazine	Biological: IMC-1121B (ramucirumab); 10 milligrams/kilogram (mg/kg) intravenously every 3 weeks in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.; Other Names: ramucirumab LY3009806 ; Drug: Dacarbazine; 1000 milligrams/square meter (mg/m2) intravenously every 3 weeks in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.; Other Names: DIC Imidazole Carboxamide

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) [Baseline up to 36 months]

   PFS was defined as the time from the first day of therapy to the first evidence of disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0) or death from any cause. Progressive disease (PD) was defined as at least a 20% increase in the sum of the longest diameter (LD) of the target lesions, taking as reference the smallest sum LD recorded since the treatment started in comparison with the measurement of the nadir or the appearance of 1 or more new lesions. In addition, unequivocal progression of existing non-target lesions was considered PD. New or existing pleural effusion/ascites required cytological confirmation for PD according to the protocol. Participants who did not progress and who were alive or did not have documented progression or missed ≥2 visits, or had no post baseline assessment were censored at the day of their last tumor assessment.

Secondary Outcome Measures

1. Number of Participants With Adverse Events (AE) [Baseline up to 40 months]

   The number of participants who experienced any IMC-1121B (ramucirumab [RAM]) treatment-related and treatment emergent AE (TEAE), treatment-related TEAE of Grade ≥3, treatment-related TE serious AEs (SAEs), treatment-related TEAE resulting in death (Grade 5 AE) and any TEAEs resulting in death. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

2. Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)] [Cycle 1 Day 1 (of 21-day cycle) up to 17.1 months]

   The ORR was defined as the percentage of all randomized participants with the best overall response of PR or CR using Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR was defined as the disappearance of all target and non-target lesions. PR was defined as at least a 30% decrease in sum of longest diameter of target lesions. CR and PR had to be confirmed by repeat assessments and performed no fewer than 4 weeks after the criteria for response were first met.

3. Duration of Response [Cycle 1 Day 1 (of 21-day cycle) up to 17.1 months]

   The duration of overall response was defined as the time from first assessment of complete response (CR) or partial response (PR) to the first date of progressive disease (PD) using Response Evaluation Criteria in Solid Tumors (RECIST v1.0), initiation of other or additional antitumor therapy, or death from any cause. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. CR and PR had to be confirmed by repeat assessments and performed no fewer than 4 weeks after the criteria for response were first met. PD was defined as at least 20% increase in sum of longest diameter of target lesions. Participants who did not relapse were censored at the day of their last objective tumor assessment.

4. Percentage of Participants With Stable Disease (SD) or Better (Disease Control Rate) at 6 Weeks [6 weeks (2 cycles of treatment)]

   Disease Control Rate (DCR) was defined as complete response (CR) plus partial response (PR) plus SD using Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR was defined as the disappearance of all target and non-target lesions and the normalization of non-target lesion tumor marker levels. PR was defined as at least a 30% decrease from baseline in sum of longest diameter of target lesions. CR and PR had to be confirmed by repeat assessments and performed no fewer than 4 weeks after the criteria for response were first met. SD was defined as: neither sufficient increase to qualify for progressive disease (PD) nor sufficient shrinkage to qualify for PR, taking as reference the smallest sum of the longest diameters recorded since treatment began. PD was defined as at least 20% increase in sum of longest diameter of target lesions.

5. Percentage of Participants With Stable Disease (SD) or Better (Disease Control Rate) at 12 Weeks [12 weeks (4 cycles of treatment)]

   Disease Control Rate (DCR) was defined as complete response (CR) plus partial response (PR) plus SD using Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR was defined as the disappearance of all target and non-target lesions and the normalization of non-target lesion tumor marker levels. PR was defined as at least a 30% decrease from baseline in sum of longest diameter of target lesions. CR and PR had to be confirmed by repeat assessments and performed no fewer than 4 weeks after the criteria for response were first met. Stable Disease (SD) was defined as: neither sufficient increase to qualify for progressive disease (PD) nor sufficient shrinkage to qualify for PR, taking as reference the smallest sum of the longest diameters recorded since treatment began. PD was defined as at least 20% increase in sum of longest diameter of target lesions.

6. Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Response Rate) at 12 Weeks [12 weeks (4 cycles of treatment)]

   Response rate was defined as a CR or a PR using Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR was defined as the disappearance of all target and non-target lesions and the normalization of non-target lesion tumor marker levels. PR was defined as at least a 30% decrease from baseline in sum of longest diameter of target lesions. CR and PR had to be confirmed by repeat assessments and performed no fewer than 4 weeks after the criteria for response were first met.

7. Maximum Concentration (Cmax) for Cycle 1 Day 1 [Cycle 1 Day 1 (21-day cycle) 1-hour post infusion]

   Cmax was not calculated due to sparse sampling.

8. Maximum Concentration (Cmax) for Cycle 1 Day 7 [Cycle 1 Day 7 (21-day cycle)]

   Cmax was not calculated due to sparse sampling.

9. Maximum Concentration (Cmax) for Cycle 1 Day 14 [Cycle 1 Day 14 (21-day cycle)]

   Cmax was not calculated due to sparse sampling.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• The participant has histologically or cytologically confirmed melanoma that is stage IV (metastatic)

• The participant has an Eastern Cooperative Oncology Performance Status (ECOG PS) of 0-1

• The participant has completed any prior radiotherapy, biologic/immunotherapy or vaccine therapy (for adjuvant or advanced disease) at least six weeks prior to the first dose of study therapy

• The participant has adequate hematological functions [absolute neutrophil count (ANC) ≥ 1500 cells/microliter (μL), hemoglobin ≥ 9 grams/deciliter (g/dL) and platelets ≥ 100,000 cells/μL].

• The participant has adequate hepatic function [bilirubin within normal limits (WNL), aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤ 2.5 times the upper limit of normal (ULN), or ≤ 5.0 times the ULN if the transaminase elevation is due to liver metastases]

• The participant has serum creatinine ≤ 1.5 x ULN [or a calculated creatinine clearance

60 milliliters/minute (mL/min)]

• The participant's urinary protein ≤ 1+ on dipstick or routine urinalysis [(UA); if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine for protein must demonstrate < 1000 milligrams (mg) of protein in 24 hours to allow participation in the study]

• The participant must have adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 1.5 X ULN

Exclusion Criteria

• The participant has mucosal or intra-ocular melanoma

• The participant has known or suspected brain or leptomeningeal metastases

• The participant has had prior cytotoxic chemotherapy for metastatic malignant melanoma

• The participant has had more than one line of biologic, immunologic or vaccine-based therapy for metastatic malignant melanoma (including therapy for adjuvant or advanced disease)

• The participant has a nonhealing wound or ulcer

• The participant has a known alcohol or drug dependency

• The participant is pregnant or breastfeeding

• The participant has a coexisting medical or psychiatric problem of sufficient severity to limit compliance with the study and/or increase the risks associated with study participation or study drug administration or interfere with the interpretation of study results

• The participant has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders in the opinion of the investigator

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ImClone Investigational Site	Decatur	Alabama	United States	35601
2	ImClone Investigational Site	Scottsdale	Arizona	United States	85258
3	ImClone Investigational Site	Scottsdale	Arizona	United States	85260
4	ImClone Investigational Site	Fresno	California	United States	93720
5	ImClone Investigational Site	San Francisco	California	United States	94109
6	ImClone Investigational Site	Aurora	Colorado	United States	80045
7	ImClone Investigational Site	Jacksonville	Florida	United States	32256
8	ImClone Investigational Site	Orlando	Florida	United States	32806
9	ImClone Investigational Site	Oxford	Mississippi	United States	38655
10	ImClone Investigational Site	Missoula	Montana	United States	59806
11	ImClone Investigational Site	Buffalo	New York	United States	14263
12	ImClone Investigational Site	New York City	New York	United States	10016
13	ImClone Investigational Site	New York	New York	United States	10021
14	ImClone Investigational Site	Willow Grove	Pennsylvania	United States	19090
15	ImClone Investigational Site	Dallas	Texas	United States	75230
16	ImClone Investigational Site	Houston	Texas	United States	77030
17	ImClone Investigational Site	Seattle	Washington	United States	98109

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: NCT00533702
• Other Study ID Numbers: 13920; CP12-0604; I4T-IE-JVBO
• First Posted: Sep 21, 2007
• Last Update Posted: Aug 1, 2014
• Last Verified: Jul 1, 2014

• Keywords provided by Eli Lilly and Company: Phase II; Melanoma; IMC-1121B; ImClone
• Additional relevant MeSH terms: Melanoma; Dacarbazine; Ramucirumab; Antibodies, Monoclonal; Imidazole

Study Results

Participant Flow

Pre-assignment Detail	Participants who completed the study were those who died or were alive but off treatment at the end of the study.

Arm/Group Title	IMC-1121B (Ramucirumab) + Dacarbazine	IMC-1121B (Ramucirumab)
Arm/Group Description	IMC-1121B (ramucirumab): 10 milligrams/kilogram (mg/kg) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria. Dacarbazine: 1000 milligrams/square meter (mg/m2) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.	IMC-1121B (ramucirumab): 10 mg/kg administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.
Period Title: Overall Study
STARTED	54	52
Received Any Quantity of Study Drug	52	50
COMPLETED	49	50
NOT COMPLETED	5	2

Baseline Characteristics

Arm/Group Title	IMC-1121B (Ramucirumab) + Dacarbazine	IMC-1121B (Ramucirumab)	Total
Arm/Group Description	IMC-1121B (ramucirumab): 10 milligrams/kilogram (mg/kg) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria. Dacarbazine: 1000 milligrams/square meter (mg/m2) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.	IMC-1121B (ramucirumab): 10 mg/kg administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.	Total of all reporting groups
Overall Participants	52	50	102
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	29 55.8%	28 56%	57 55.9%
>=65 years	23 44.2%	22 44%	45 44.1%
Sex: Female, Male (Count of Participants)
Female	15 28.8%	12 24%	27 26.5%
Male	37 71.2%	38 76%	75 73.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 9.6%	1 2%	6 5.9%
Not Hispanic or Latino	47 90.4%	49 98%	96 94.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	52 100%	50 100%	102 100%
Race (participants) [Number]
Asian	1 1.9%	0 0%	1 1%
White	50 96.2%	50 100%	100 98%
Other	1 1.9%	0 0%	1 1%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	PFS was defined as the time from the first day of therapy to the first evidence of disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0) or death from any cause. Progressive disease (PD) was defined as at least a 20% increase in the sum of the longest diameter (LD) of the target lesions, taking as reference the smallest sum LD recorded since the treatment started in comparison with the measurement of the nadir or the appearance of 1 or more new lesions. In addition, unequivocal progression of existing non-target lesions was considered PD. New or existing pleural effusion/ascites required cytological confirmation for PD according to the protocol. Participants who did not progress and who were alive or did not have documented progression or missed ≥2 visits, or had no post baseline assessment were censored at the day of their last tumor assessment.
Time Frame	Baseline up to 36 months

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: All enrolled participants who were treated with any quantity of study drug. Censored participants: IMC-1121B (ramucirumab) + dacarbazine=9; IMC-1121B (ramucirumab)=4.

Arm/Group Title	IMC-1121B (Ramucirumab) + Dacarbazine	IMC-1121B (Ramucirumab)
Arm/Group Description	IMC-1121B (ramucirumab): 10 milligrams/kilogram (mg/kg) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria. Dacarbazine: 1000 milligrams/square meter (mg/m2) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.	IMC-1121B (ramucirumab): 10 mg/kg administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.
Measure Participants	52	50
Median (95% Confidence Interval) [months]	2.6	1.7

2. Secondary Outcome

Title	Number of Participants With Adverse Events (AE)
Description	The number of participants who experienced any IMC-1121B (ramucirumab [RAM]) treatment-related and treatment emergent AE (TEAE), treatment-related TEAE of Grade ≥3, treatment-related TE serious AEs (SAEs), treatment-related TEAE resulting in death (Grade 5 AE) and any TEAEs resulting in death. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time Frame	Baseline up to 40 months

Outcome Measure Data

Analysis Population Description

Safety Population: All enrolled participants who were treated with any quantity of study drug.

Arm/Group Title	IMC-1121B (Ramucirumab) + Dacarbazine	IMC-1121B (Ramucirumab)
Arm/Group Description	IMC-1121B (ramucirumab): 10 milligrams/kilogram (mg/kg) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria. Dacarbazine: 1000 milligrams/square meter (mg/m2) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.	IMC-1121B (ramucirumab): 10 mg/kg administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.
Measure Participants	52	50
Any RAM related TEAE	43 82.7%	40 80%
RAM related SAE	9 17.3%	5 10%
RAM related ≥ Grade 3 AE	20 38.5%	13 26%
RAM related death	1 1.9%	1 2%
RAM related TEAE leading to discontinuation of RAM	3 5.8%	4 8%
Any AE with outcome of death	2 3.8%	2 4%

3. Secondary Outcome

Title	Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]
Description	The ORR was defined as the percentage of all randomized participants with the best overall response of PR or CR using Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR was defined as the disappearance of all target and non-target lesions. PR was defined as at least a 30% decrease in sum of longest diameter of target lesions. CR and PR had to be confirmed by repeat assessments and performed no fewer than 4 weeks after the criteria for response were first met.
Time Frame	Cycle 1 Day 1 (of 21-day cycle) up to 17.1 months

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: All enrolled participants who were treated with any quantity of study drug.

Arm/Group Title	IMC-1121B (Ramucirumab) + Dacarbazine	IMC-1121B (Ramucirumab)
Arm/Group Description	IMC-1121B (ramucirumab): 10 milligrams/kilogram (mg/kg) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria. Dacarbazine: 1000 milligrams/square meter (mg/m2) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.	IMC-1121B (ramucirumab): 10 mg/kg administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.
Measure Participants	52	50
Number (95% Confidence Interval) [percentage of participants]	17.3 33.3%	4.0 8%

4. Secondary Outcome

Title	Duration of Response
Description	The duration of overall response was defined as the time from first assessment of complete response (CR) or partial response (PR) to the first date of progressive disease (PD) using Response Evaluation Criteria in Solid Tumors (RECIST v1.0), initiation of other or additional antitumor therapy, or death from any cause. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. CR and PR had to be confirmed by repeat assessments and performed no fewer than 4 weeks after the criteria for response were first met. PD was defined as at least 20% increase in sum of longest diameter of target lesions. Participants who did not relapse were censored at the day of their last objective tumor assessment.
Time Frame	Cycle 1 Day 1 (of 21-day cycle) up to 17.1 months

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: All enrolled participants who were treated with any quantity of study drug and who had CR or PR. Censored participants: IMC-1121B (ramucirumab) + dacarbazine=2; IMC-1121B (ramucirumab)=0.

Arm/Group Title	IMC-1121B (Ramucirumab) + Dacarbazine	IMC-1121B (Ramucirumab)
Arm/Group Description	IMC-1121B (ramucirumab): 10 milligrams/kilogram (mg/kg) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria. Dacarbazine: 1000 milligrams/square meter (mg/m2) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.	IMC-1121B (ramucirumab): 10 mg/kg administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.
Measure Participants	9	2
Median (95% Confidence Interval) [months]	11.0	NA

5. Secondary Outcome

Title	Percentage of Participants With Stable Disease (SD) or Better (Disease Control Rate) at 6 Weeks
Description	Disease Control Rate (DCR) was defined as complete response (CR) plus partial response (PR) plus SD using Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR was defined as the disappearance of all target and non-target lesions and the normalization of non-target lesion tumor marker levels. PR was defined as at least a 30% decrease from baseline in sum of longest diameter of target lesions. CR and PR had to be confirmed by repeat assessments and performed no fewer than 4 weeks after the criteria for response were first met. SD was defined as: neither sufficient increase to qualify for progressive disease (PD) nor sufficient shrinkage to qualify for PR, taking as reference the smallest sum of the longest diameters recorded since treatment began. PD was defined as at least 20% increase in sum of longest diameter of target lesions.
Time Frame	6 weeks (2 cycles of treatment)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: All enrolled participants who were treated with any quantity of study drug.

Arm/Group Title	IMC-1121B (Ramucirumab) + Dacarbazine	IMC-1121B (Ramucirumab)
Arm/Group Description	IMC-1121B (ramucirumab): 10 milligrams/kilogram (mg/kg) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria. Dacarbazine: 1000 milligrams/square meter (mg/m2) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.	IMC-1121B (ramucirumab): 10 mg/kg administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.
Measure Participants	52	50
Number [percentage of participants]	54 103.8%	44 88%

6. Secondary Outcome

Title	Percentage of Participants With Stable Disease (SD) or Better (Disease Control Rate) at 12 Weeks
Description	Disease Control Rate (DCR) was defined as complete response (CR) plus partial response (PR) plus SD using Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR was defined as the disappearance of all target and non-target lesions and the normalization of non-target lesion tumor marker levels. PR was defined as at least a 30% decrease from baseline in sum of longest diameter of target lesions. CR and PR had to be confirmed by repeat assessments and performed no fewer than 4 weeks after the criteria for response were first met. Stable Disease (SD) was defined as: neither sufficient increase to qualify for progressive disease (PD) nor sufficient shrinkage to qualify for PR, taking as reference the smallest sum of the longest diameters recorded since treatment began. PD was defined as at least 20% increase in sum of longest diameter of target lesions.
Time Frame	12 weeks (4 cycles of treatment)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: All enrolled participants who were treated with any quantity of study drug.

Arm/Group Title	IMC-1121B (Ramucirumab) + Dacarbazine	IMC-1121B (Ramucirumab)
Arm/Group Description	IMC-1121B (ramucirumab): 10 milligrams/kilogram (mg/kg) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria. Dacarbazine: 1000 milligrams/square meter (mg/m2) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.	IMC-1121B (ramucirumab): 10 mg/kg administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.
Measure Participants	52	50
Number [percentage of participants]	40 76.9%	24 48%

7. Secondary Outcome

Title	Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Response Rate) at 12 Weeks
Description	Response rate was defined as a CR or a PR using Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR was defined as the disappearance of all target and non-target lesions and the normalization of non-target lesion tumor marker levels. PR was defined as at least a 30% decrease from baseline in sum of longest diameter of target lesions. CR and PR had to be confirmed by repeat assessments and performed no fewer than 4 weeks after the criteria for response were first met.
Time Frame	12 weeks (4 cycles of treatment)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population: All enrolled participants who were treated with any quantity of study drug.

Arm/Group Title	IMC-1121B (Ramucirumab) + Dacarbazine	IMC-1121B (Ramucirumab)
Arm/Group Description	IMC-1121B (ramucirumab): 10 milligrams/kilogram (mg/kg) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria. Dacarbazine: 1000 milligrams/square meter (mg/m2) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.	IMC-1121B (ramucirumab): 10 mg/kg administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.
Measure Participants	52	50
Number [percentage of participants]	13.5 26%	4.0 8%

8. Secondary Outcome

Title	Maximum Concentration (Cmax) for Cycle 1 Day 1
Description	Cmax was not calculated due to sparse sampling.
Time Frame	Cycle 1 Day 1 (21-day cycle) 1-hour post infusion

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed.

Arm/Group Title	IMC-1121B (Ramucirumab) + Dacarbazine	IMC-1121B (Ramucirumab)
Arm/Group Description	IMC-1121B (ramucirumab): 10 milligrams/kilogram (mg/kg) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria. Dacarbazine: 1000 milligrams/square meter (mg/m2) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.	IMC-1121B (ramucirumab): 10 mg/kg administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.
Measure Participants	0	0

9. Secondary Outcome

Title	Maximum Concentration (Cmax) for Cycle 1 Day 7
Description	Cmax was not calculated due to sparse sampling.
Time Frame	Cycle 1 Day 7 (21-day cycle)

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed.

Arm/Group Title	IMC-1121B (Ramucirumab) + Dacarbazine	IMC-1121B (Ramucirumab)
Arm/Group Description	IMC-1121B (ramucirumab): 10 milligrams/kilogram (mg/kg) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria. Dacarbazine: 1000 milligrams/square meter (mg/m2) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.	IMC-1121B (ramucirumab): 10 mg/kg administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.
Measure Participants	0	0

10. Secondary Outcome

Title	Maximum Concentration (Cmax) for Cycle 1 Day 14
Description	Cmax was not calculated due to sparse sampling.
Time Frame	Cycle 1 Day 14 (21-day cycle)

Outcome Measure Data

Analysis Population Description

Zero participants were analyzed.

Arm/Group Title	IMC-1121B (Ramucirumab) + Dacarbazine	IMC-1121B (Ramucirumab)
Arm/Group Description	IMC-1121B (ramucirumab): 10 milligrams/kilogram (mg/kg) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria. Dacarbazine: 1000 milligrams/square meter (mg/m2) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.	IMC-1121B (ramucirumab): 10 mg/kg administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.
Measure Participants	0	0

Adverse Events

Arm/Group Title	IMC-1121B (Ramucirumab) + Dacarbazine		IMC-1121B (Ramucirumab)
Arm/Group Description	IMC-1121B (ramucirumab): 10 milligrams/kilogram (mg/kg) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria. Dacarbazine: 1000 milligrams/square meter (mg/m2) administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.		IMC-1121B (ramucirumab): 10 mg/kg administered intravenously on Day 1 of 21-day cycle in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.
All Cause Mortality
	IMC-1121B (Ramucirumab) + Dacarbazine		IMC-1121B (Ramucirumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IMC-1121B (Ramucirumab) + Dacarbazine		IMC-1121B (Ramucirumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/52 (26.9%)		15/50 (30%)
Blood and lymphatic system disorders
Febrile neutropenia	1/52 (1.9%)	1	0/50 (0%)	0
Cardiac disorders
Cardiac arrest	1/52 (1.9%)	1	0/50 (0%)	0
Coronary artery disease	0/52 (0%)	0	1/50 (2%)	1
Myocardial infarction	0/52 (0%)	0	1/50 (2%)	1
Supraventricular tachycardia	0/52 (0%)	0	1/50 (2%)	1
Gastrointestinal disorders
Abdominal pain	0/52 (0%)	0	2/50 (4%)	2
Intestinal obstruction	1/52 (1.9%)	1	0/50 (0%)	0
Proctalgia	1/52 (1.9%)	1	0/50 (0%)	0
Vomiting	0/52 (0%)	0	1/50 (2%)	1
General disorders
Chest pain	1/52 (1.9%)	1	0/50 (0%)	0
Infusion related reaction	0/52 (0%)	0	3/50 (6%)	3
Hepatobiliary disorders
Hepatic failure	0/52 (0%)	0	2/50 (4%)	3
Jaundice	0/52 (0%)	0	1/50 (2%)	1
Infections and infestations
Diverticulitis	1/52 (1.9%)	1	0/50 (0%)	0
Infection	1/52 (1.9%)	1	0/50 (0%)	0
Pneumonia	1/52 (1.9%)	1	0/50 (0%)	0
Injury, poisoning and procedural complications
Rib fracture	1/52 (1.9%)	1	0/50 (0%)	0
Spinal compression fracture	1/52 (1.9%)	1	0/50 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/52 (0%)	0	1/50 (2%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/52 (0%)	0	1/50 (2%)	1
Pain in extremity	0/52 (0%)	0	1/50 (2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic malignant melanoma	1/52 (1.9%)	1	0/50 (0%)	0
Tumour haemorrhage	1/52 (1.9%)	1	0/50 (0%)	0
Nervous system disorders
Cerebral haemorrhage	1/52 (1.9%)	1	0/50 (0%)	0
Convulsion	0/52 (0%)	0	1/50 (2%)	1
Syncope	1/52 (1.9%)	1	1/50 (2%)	1
Psychiatric disorders
Confusional state	1/52 (1.9%)	1	0/50 (0%)	0
Psychotic disorder	0/52 (0%)	0	1/50 (2%)	1
Renal and urinary disorders
Proteinuria	0/52 (0%)	0	1/50 (2%)	1
Renal failure acute	1/52 (1.9%)	1	0/50 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchospasm	0/52 (0%)	0	1/50 (2%)	1
Epistaxis	1/52 (1.9%)	1	0/50 (0%)	0
Hypoxia	1/52 (1.9%)	1	0/50 (0%)	0
Pulmonary embolism	0/52 (0%)	0	1/50 (2%)	1
Vascular disorders
Flushing	0/52 (0%)	0	1/50 (2%)	1
Hypertension	1/52 (1.9%)	1	0/50 (0%)	0
Hypotension	0/52 (0%)	0	1/50 (2%)	1
Pelvic venous thrombosis	1/52 (1.9%)	1	0/50 (0%)	0
Other (Not Including Serious) Adverse Events
	IMC-1121B (Ramucirumab) + Dacarbazine		IMC-1121B (Ramucirumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	52/52 (100%)		48/50 (96%)
Blood and lymphatic system disorders
Anaemia	7/52 (13.5%)	22	2/50 (4%)	4
Leukopenia	5/52 (9.6%)	15	1/50 (2%)	1
Neutropenia	18/52 (34.6%)	29	0/50 (0%)	0
Thrombocytopenia	20/52 (38.5%)	54	4/50 (8%)	7
Eye disorders
Vision blurred	1/52 (1.9%)	1	3/50 (6%)	4
Gastrointestinal disorders
Abdominal pain	5/52 (9.6%)	6	6/50 (12%)	6
Abdominal pain upper	3/52 (5.8%)	3	2/50 (4%)	2
Constipation	16/52 (30.8%)	23	10/50 (20%)	10
Diarrhoea	10/52 (19.2%)	13	8/50 (16%)	10
Dry mouth	4/52 (7.7%)	5	0/50 (0%)	0
Dyspepsia	2/52 (3.8%)	2	3/50 (6%)	3
Gingival bleeding	3/52 (5.8%)	3	4/50 (8%)	4
Nausea	20/52 (38.5%)	36	14/50 (28%)	19
Vomiting	7/52 (13.5%)	9	11/50 (22%)	12
General disorders
Chest pain	3/52 (5.8%)	3	2/50 (4%)	2
Chills	6/52 (11.5%)	7	8/50 (16%)	8
Fatigue	33/52 (63.5%)	63	28/50 (56%)	38
Infusion related reaction	4/52 (7.7%)	4	4/50 (8%)	5
Infusion site pain	3/52 (5.8%)	3	0/50 (0%)	0
Injection site irritation	4/52 (7.7%)	8	0/50 (0%)	0
Oedema peripheral	15/52 (28.8%)	27	10/50 (20%)	12
Pain	4/52 (7.7%)	4	2/50 (4%)	2
Pyrexia	2/52 (3.8%)	3	8/50 (16%)	8
Infections and infestations
Upper respiratory tract infection	6/52 (11.5%)	7	1/50 (2%)	1
Investigations
Weight decreased	2/52 (3.8%)	2	5/50 (10%)	12
Metabolism and nutrition disorders
Anorexia	14/52 (26.9%)	15	7/50 (14%)	8
Dehydration	5/52 (9.6%)	5	3/50 (6%)	4
Hypokalaemia	3/52 (5.8%)	5	1/50 (2%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	5/52 (9.6%)	6	6/50 (12%)	6
Back pain	9/52 (17.3%)	10	9/50 (18%)	14
Muscle spasms	4/52 (7.7%)	5	1/50 (2%)	1
Muscular weakness	3/52 (5.8%)	3	1/50 (2%)	1
Musculoskeletal chest pain	4/52 (7.7%)	7	2/50 (4%)	2
Musculoskeletal pain	4/52 (7.7%)	7	3/50 (6%)	3
Pain in extremity	6/52 (11.5%)	7	2/50 (4%)	2
Nervous system disorders
Dizziness	3/52 (5.8%)	5	2/50 (4%)	2
Dysgeusia	5/52 (9.6%)	6	3/50 (6%)	3
Headache	9/52 (17.3%)	18	16/50 (32%)	21
Paraesthesia	1/52 (1.9%)	1	3/50 (6%)	3
Psychiatric disorders
Anxiety	5/52 (9.6%)	6	4/50 (8%)	4
Depression	4/52 (7.7%)	4	4/50 (8%)	4
Insomnia	9/52 (17.3%)	9	5/50 (10%)	5
Renal and urinary disorders
Dysuria	0/52 (0%)	0	4/50 (8%)	5
Proteinuria	4/52 (7.7%)	8	6/50 (12%)	17
Respiratory, thoracic and mediastinal disorders
Cough	6/52 (11.5%)	8	5/50 (10%)	7
Dysphonia	3/52 (5.8%)	3	2/50 (4%)	2
Dyspnoea	14/52 (26.9%)	16	4/50 (8%)	4
Dyspnoea exertional	3/52 (5.8%)	3	3/50 (6%)	3
Epistaxis	7/52 (13.5%)	12	4/50 (8%)	4
Hiccups	3/52 (5.8%)	3	0/50 (0%)	0
Nasal congestion	3/52 (5.8%)	6	1/50 (2%)	1
Productive cough	2/52 (3.8%)	2	3/50 (6%)	3
Skin and subcutaneous tissue disorders
Alopecia	3/52 (5.8%)	5	1/50 (2%)	1
Dry skin	3/52 (5.8%)	3	4/50 (8%)	4
Erythema	4/52 (7.7%)	5	3/50 (6%)	7
Hyperhidrosis	3/52 (5.8%)	5	1/50 (2%)	1
Pruritus	6/52 (11.5%)	10	4/50 (8%)	4
Rash	8/52 (15.4%)	12	8/50 (16%)	11
Vitiligo	3/52 (5.8%)	3	0/50 (0%)	0
Vascular disorders
Flushing	3/52 (5.8%)	3	1/50 (2%)	1
Hypertension	12/52 (23.1%)	18	12/50 (24%)	19

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.