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A Trial of ABI-007 Versus Dacarbazine in Previously Untreated Patients With Metastatic Malignant Melanoma

This study has been completed.
Sponsor:
Collaborator:
University of Arizona
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00864253
First received: March 16, 2009
Last updated: May 13, 2014
Last verified: May 2014
Results First Received: April 16, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Malignant Melanoma
Interventions: Drug: ABI-007
Drug: Dacarbazine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This multicenter study was conducted by investigators in 9 countries: Australia, Canada, France, Germany, Italy, Netherlands, Spain, United Kingdom and the United States (US) and treatment was given on an outpatient basis. First participant enrolled 30 April 2011, last participant enrolled June 2011..

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomized in a 1:1 ratio. Randomization was stratified based on metastatic stage (M1a, M1b, and M1c), region (North America, Western Europe and Australia), and baseline lactate dehydrogenase (LDH) (< 0.8 * ULN, 0.8–1.1 * ULN, >1.1-2 * ULN).

Reporting Groups
  Description
ABI-007 150mg/m^2 ABI-007 150mg/m^2 intravenously over approximately 30 minutes on Days 1, 8 and 15 of each 28 day cycle
Dacarbazine 1000mg/m^2 Dacarbazine 1000mg/m^2 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.

Participant Flow:   Overall Study
    ABI-007 150mg/m^2     Dacarbazine 1000mg/m^2  
STARTED     264     265  
Treated     257     258  
COMPLETED     165 [1]   207 [1]
NOT COMPLETED     99     58  
Adverse Event                 56                 11  
Unrelated Adverse Event                 3                 1  
Physician Decision                 11                 15  
Protocol Violation                 0                 2  
Lost to Follow-up                 1                 1  
Withdrawal by Subject                 18                 18  
Death                 1                 0  
Ongoing                 2                 3  
Untreated                 7                 7  
[1] Completed = defined as discontinuation due to progressive disease



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: The ITT population consisted of all randomized participants regardless of whether the participant received any study drug or had any efficacy assessments collected.

Reporting Groups
  Description
ABI-007 150mg/m^2 ABI-007 150mg/m^2 intravenously over approximately 30 minutes on Days 1, 8 and 15 of each 28 day cycle
Dacarbazine Arm B 1000mg/m^2 Dacarbazine 1000mg/m^2 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.
Total Total of all reporting groups

Baseline Measures
    ABI-007 150mg/m^2     Dacarbazine Arm B 1000mg/m^2     Total  
Number of Participants  
[units: participants]
  264     265     529  
Age  
[units: years]
Median ( Full Range )
  62.0  
  ( 21 to 85 )  
  64.0  
  ( 28 to 87 )  
  63.0  
  ( 21 to 87 )  
Gender  
[units: participants]
     
Female     91     91     182  
Male     173     174     347  
Eastern Cooperative Oncology Group Performance Status [1]
[units: participants]
     
0 = Fully Active     195     181     376  
1= Restrictive but Ambulatory     68     82     150  
2 = Ambulatory but Unable to Work     1     2     3  
3 = Limited Self-Care     0     0     0  
4 = Completely Disabled     0     0     0  
Baseline Lactate Dehydrogenase value [2]
[units: participants]
     
<0.8 * Upper Limit of Normal (ULN)     138     139     277  
0.8-1.1 * ULN     72     69     141  
>1.1-2 * ULN     51     56     107  
>2 * ULN     3     1     4  
Metastatic Stage [3]
[units: participants]
     
M1a     27     21     48  
M1b     66     69     135  
M1c     171     175     346  
BRAF Status [4]
[units: participants]
     
V 600 E     65     67     132  
Wild Type (mutation negative)     116     108     224  
unknown     83     90     173  
[1] ECOG-Eastern Cooperative Oncology Group (ECOG) Performance Status is used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. 0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity)
[2] The serum level of Lactate Dehydrogenase (LDH) is considered a risk factor for overall survival in participants with metastatic melanoma. LDH is a blood test used as a general indicator of the existence and severity of acute or chronic tissue damage and used to monitor cancers such as metastatic melanoma. The baseline LDH value was considered to be the last central laboratory LDH value before randomization. If the central laboratory data was not available, the last non-missing local laboratory value before randomization was used.
[3] Distant Metastatic (M) Stages: MX: Distant metastasis cannot be assessed; M0: No distant metastasis; M1= Distant metastasis; M1a: Metastasis to skin, subcutaneous tissues or distant lymph nodes; M1b: metastasis to lung; M1c: metastasis to all other visceral sites or distant metastasis at any site associated with an elevated serum lactic dehyrogenase
[4] BRAF is a mutation biomarker for melanoma, a human gene that makes the protein B-Raf. The gene is referred to as a protoco-oncogene B Raf and vRaf murine sarcoma viral oncogene homolog B1, while the protein is known as serine/threonine-protein kinase B-Raf. The protein is involved in sending signals inside cells and in directing cell growth. These BRAF mutations were associated with features of high risk melanoma, including truncal primary, earlier age of onset, lack of chronic skin damage and shortened survival. The BRAF statuses included: Wild type and V600E mutation.



  Outcome Measures
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1.  Primary:   Progression Free Survival (PFS) Based on a Blinded Radiology Assessment of Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines   [ Time Frame: Response assessment completed every 8 weeks until disease progression for up to 106 weeks; data cut off 30 June 2012 ]

2.  Secondary:   Participant Survival   [ Time Frame: Up to 38 months; Up to data cut off of 30 June 2012 ]

3.  Secondary:   Summary of Treatment-emergent Adverse Events (AEs)   [ Time Frame: Maximum exposure to study drug was 106 weeks; up to data cut off of 30 June 2012 ]

4.  Secondary:   Number of Participants Experiencing Dose Reductions, or Dose Interruptions, or Dose Delays of Study Drug   [ Time Frame: Maximum study drug exposure 106 weeks; data cut off 30 June 2012 ]

5.  Secondary:   Nadir for the Absolute Neutrophil Count (ANC) Measurements   [ Time Frame: Day 1 up to 106 weeks; up to data cut off 30 June 2012 ]

6.  Secondary:   Nadir for White Blood Cells (WBCs) Measurements   [ Time Frame: Day 1 up to 106 weeks; up to data cut off 30 June 2012 ]

7.  Secondary:   Nadir for Platelet Count Measurements.   [ Time Frame: Day 1 up to 106 weeks; up to data cut off 30 June 2012 ]

8.  Secondary:   Nadir for the Hemoglobin Count Measurements   [ Time Frame: Day 1 up to 106 weeks; up to data cut off 30 June 2012 ]

9.  Secondary:   Pharmacokinetic Parameters   [ Time Frame: On Cycle 1, Day 1 blood samples were taken at 0.25, 3.5, and 24 hr post-infusion end of the initial dose ]

10.  Other Pre-specified:   Progression-free Survival (PFS) Based on Investigator Assessment Using RECIST Response Guidelines   [ Time Frame: Response assessments completed every 8 weeks until disease progression; up to data cut off 30 June 2012; 38 months ]

11.  Other Pre-specified:   Percent of Participants Who Achieve an Objective Confirmed Complete or Partial Response Based on Blinded Radiology Assessment of Response by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0   [ Time Frame: every 8 weeks; up to data cut off 30 June 2012 ]

12.  Other Pre-specified:   Percent of Participants With Stable Disease (SD) for ≥ 16 Weeks, or Confirmed Complete or Partial Response (i.e., Disease Control) Based on a Blinded Radiology Assessment of Response   [ Time Frame: Response assessment completed every 8 weeks until disease progression; up to data cut-off 30 June 2012 ]

13.  Other Pre-specified:   Duration of Response (DOR) in Responding Participants   [ Time Frame: up to data cut off 30 June 2012 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Participation in the PK sampling for participants randomized to the ABI-007 arm was optional; too few samples were available to support the analysis


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Anne McClain
Organization: Celgene Corporation
phone: 888-260-1599
e-mail: clinicaltrialdisclosure@celgene.com


No publications provided


Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00864253     History of Changes
Other Study ID Numbers: CA033
Study First Received: March 16, 2009
Results First Received: April 16, 2014
Last Updated: May 13, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Australia: Human Research Ethics Committee
New Zealand: Medsafe