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

Metastatic Malignant Melanoma Clinical Trial

Official title:

Phase II Randomized, Open-Label Study of IMC-1121B With or Without Dacarbazine in Patients With Metastatic Malignant Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00533702
• Other study ID #: 13920
• Secondary ID: CP12-0604I4T-IE-
• Status: Completed
• Phase: Phase 2
• First received: September 17, 2007
• Last updated: July 29, 2014
• Start date: November 2007
• Est. completion date: May 2011

Study information

• Verified date: July 2014
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Melanoma
• Metastatic Malignant Melanoma

Intervention

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.

Drug:
• Dacarbazine
1000 milligrams/square meter (mg/m2) intravenously every 3 weeks in the absence of disease progression, unacceptable toxicity, or other withdrawal criteria.

Locations

Country	Name	City	State
United States	ImClone Investigational Site	Aurora	Colorado
United States	ImClone Investigational Site	Buffalo	New York
United States	ImClone Investigational Site	Dallas	Texas
United States	ImClone Investigational Site	Decatur	Alabama
United States	ImClone Investigational Site	Fresno	California
United States	ImClone Investigational Site	Houston	Texas
United States	ImClone Investigational Site	Jacksonville	Florida
United States	ImClone Investigational Site	Missoula	Montana
United States	ImClone Investigational Site	New York	New York
United States	ImClone Investigational Site	New York City	New York
United States	ImClone Investigational Site	Orlando	Florida
United States	ImClone Investigational Site	Oxford	Mississippi
United States	ImClone Investigational Site	San Francisco	California
United States	ImClone Investigational Site	Scottsdale	Arizona
United States	ImClone Investigational Site	Scottsdale	Arizona
United States	ImClone Investigational Site	Seattle	Washington
United States	ImClone Investigational Site	Willow Grove	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline up to 36 months	No
Secondary	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.	Baseline up to 40 months	Yes
Secondary	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.	Cycle 1 Day 1 (of 21-day cycle) up to 17.1 months	No
Secondary	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.	Cycle 1 Day 1 (of 21-day cycle) up to 17.1 months	No
Secondary	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.	6 weeks (2 cycles of treatment)	No
Secondary	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.	12 weeks (4 cycles of treatment)	No
Secondary	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.	12 weeks (4 cycles of treatment)	No
Secondary	Maximum Concentration (Cmax) for Cycle 1 Day 1	Cmax was not calculated due to sparse sampling.	Cycle 1 Day 1 (21-day cycle) 1-hour post infusion	No
Secondary	Maximum Concentration (Cmax) for Cycle 1 Day 7	Cmax was not calculated due to sparse sampling.	Cycle 1 Day 7 (21-day cycle)	No
Secondary	Maximum Concentration (Cmax) for Cycle 1 Day 14	Cmax was not calculated due to sparse sampling.	Cycle 1 Day 14 (21-day cycle)	No