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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00533702
First received: September 17, 2007
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Metastatic Malignant Melanoma
Biological: IMC-1121B (ramucirumab)
Drug: Dacarbazine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Baseline up to 36 months ] [ Designated as safety issue: No ]
    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. 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) [ Time Frame: Baseline up to 40 months ] [ Designated as safety issue: Yes ]
    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)] [ Time Frame: Cycle 1 Day 1 (of 21-day cycle) up to 17.1 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 1 Day 1 (of 21-day cycle) up to 17.1 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 weeks (2 cycles of treatment) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks (4 cycles of treatment) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks (4 cycles of treatment) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Cycle 1 Day 1 (21-day cycle) 1-hour post infusion ] [ Designated as safety issue: No ]
    Cmax was not calculated due to sparse sampling.

  • Maximum Concentration (Cmax) for Cycle 1 Day 7 [ Time Frame: Cycle 1 Day 7 (21-day cycle) ] [ Designated as safety issue: No ]
    Cmax was not calculated due to sparse sampling.

  • Maximum Concentration (Cmax) for Cycle 1 Day 14 [ Time Frame: Cycle 1 Day 14 (21-day cycle) ] [ Designated as safety issue: No ]
    Cmax was not calculated due to sparse sampling.


Enrollment: 106
Study Start Date: November 2007
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00533702

Locations
United States, Alabama
ImClone Investigational Site
Decatur, Alabama, United States, 35601
United States, Arizona
ImClone Investigational Site
Scottsdale, Arizona, United States, 85260
ImClone Investigational Site
Scottsdale, Arizona, United States, 85258
United States, California
ImClone Investigational Site
Fresno, California, United States, 93720
ImClone Investigational Site
San Francisco, California, United States, 94109
United States, Colorado
ImClone Investigational Site
Aurora, Colorado, United States, 80045
United States, Florida
ImClone Investigational Site
Jacksonville, Florida, United States, 32256
ImClone Investigational Site
Orlando, Florida, United States, 32806
United States, Mississippi
ImClone Investigational Site
Oxford, Mississippi, United States, 38655
United States, Montana
ImClone Investigational Site
Missoula, Montana, United States, 59806
United States, New York
ImClone Investigational Site
Buffalo, New York, United States, 14263
ImClone Investigational Site
New York, New York, United States, 10021
ImClone Investigational Site
New York City, New York, United States, 10016
United States, Pennsylvania
ImClone Investigational Site
Willow Grove, Pennsylvania, United States, 19090
United States, Texas
ImClone Investigational Site
Dallas, Texas, United States, 75230
ImClone Investigational Site
Houston, Texas, United States, 77030
United States, Washington
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00533702     History of Changes
Other Study ID Numbers: 13920, CP12-0604, I4T-IE-JVBO
Study First Received: September 17, 2007
Results First Received: May 16, 2014
Last Updated: May 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Phase II
Melanoma
IMC-1121B
ImClone

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014