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

Primary Purpose

Metastatic Malignant Melanoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
IMC-1121B (ramucirumab)
Dacarbazine
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Malignant Melanoma focused on measuring Phase II, Melanoma, IMC-1121B, ImClone

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site
  • ImClone Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

IMC-1121B (ramucirumab)

IMC-1121B (ramucirumab) + dacarbazine

Arm Description

IMC-1121B (ramucirumab)

IMC-1121B (ramucirumab) + dacarbazine

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS)
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

Number of Participants With Adverse Events (AE)
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.
Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]
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.
Duration of Response
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.
Percentage of Participants With Stable Disease (SD) or Better (Disease Control Rate) at 6 Weeks
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.
Percentage of Participants With Stable Disease (SD) or Better (Disease Control Rate) at 12 Weeks
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.
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Response Rate) at 12 Weeks
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.
Maximum Concentration (Cmax) for Cycle 1 Day 1
Cmax was not calculated due to sparse sampling.
Maximum Concentration (Cmax) for Cycle 1 Day 7
Cmax was not calculated due to sparse sampling.
Maximum Concentration (Cmax) for Cycle 1 Day 14
Cmax was not calculated due to sparse sampling.

Full Information

First Posted
September 17, 2007
Last Updated
July 29, 2014
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT00533702
Brief Title
A Study of IMC-1121B (Ramucirumab) With or Without Dacarbazine in Metastatic Malignant Melanoma
Official Title
Phase II Randomized, Open-Label Study of IMC-1121B With or Without Dacarbazine in Patients With Metastatic Malignant Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
November 2007 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Malignant Melanoma
Keywords
Phase II, Melanoma, IMC-1121B, ImClone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
106 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IMC-1121B (ramucirumab)
Arm Type
Experimental
Arm Description
IMC-1121B (ramucirumab)
Arm Title
IMC-1121B (ramucirumab) + dacarbazine
Arm Type
Active Comparator
Arm Description
IMC-1121B (ramucirumab) + dacarbazine
Intervention Type
Biological
Intervention Name(s)
IMC-1121B (ramucirumab)
Other Intervention Name(s)
ramucirumab, LY3009806
Intervention Description
10 milligrams/kilogram (mg/kg) intravenously every 3 weeks in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.
Intervention Type
Drug
Intervention Name(s)
Dacarbazine
Other Intervention Name(s)
DIC, Imidazole, Carboxamide
Intervention Description
1000 milligrams/square meter (mg/m2) intravenously every 3 weeks in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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
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)
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)
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)
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
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)
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
ImClone Investigational Site
City
Decatur
State/Province
Alabama
ZIP/Postal Code
35601
Country
United States
Facility Name
ImClone Investigational Site
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
ImClone Investigational Site
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85260
Country
United States
Facility Name
ImClone Investigational Site
City
Fresno
State/Province
California
ZIP/Postal Code
93720
Country
United States
Facility Name
ImClone Investigational Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94109
Country
United States
Facility Name
ImClone Investigational Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
ImClone Investigational Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32256
Country
United States
Facility Name
ImClone Investigational Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
ImClone Investigational Site
City
Oxford
State/Province
Mississippi
ZIP/Postal Code
38655
Country
United States
Facility Name
ImClone Investigational Site
City
Missoula
State/Province
Montana
ZIP/Postal Code
59806
Country
United States
Facility Name
ImClone Investigational Site
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
ImClone Investigational Site
City
New York City
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
ImClone Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
ImClone Investigational Site
City
Willow Grove
State/Province
Pennsylvania
ZIP/Postal Code
19090
Country
United States
Facility Name
ImClone Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
ImClone Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
ImClone Investigational Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24930625
Citation
Carvajal RD, Wong MK, Thompson JA, Gordon MS, Lewis KD, Pavlick AC, Wolchok JD, Rojas PB, Schwartz JD, Bedikian AY. A phase 2 randomised study of ramucirumab (IMC-1121B) with or without dacarbazine in patients with metastatic melanoma. Eur J Cancer. 2014 Aug;50(12):2099-107. doi: 10.1016/j.ejca.2014.03.289. Epub 2014 Jun 12.
Results Reference
derived

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

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