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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 ( Celgene Corporation )
ClinicalTrials.gov Identifier:
NCT00864253
First received: March 16, 2009
Last updated: July 31, 2015
Last verified: July 2015
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 
Overall Participants Analyzed 
[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 
[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)
Baseline Lactate Dehydrogenase value [1] 
[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 
[1] 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.
Metastatic Stage [1] 
[Units: Participants]
     
M1a   27   21   48 
M1b   66   69   135 
M1c   171   175   346 
[1] 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
BRAF Status [1] 
[Units: Participants]
     
V 600 E   65   67   132 
Wild Type (mutation negative)   116   108   224 
unknown   83   90   173 
[1] 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



Responsible Party: Celgene ( 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: July 31, 2015
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Australia: Human Research Ethics Committee
New Zealand: Medsafe