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

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

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)
Sex: Female, Male  [Units: Participants] Count of Participants
Female	91  34.5%	91  34.3%	182  34.4%
Male	173  65.5%	174  65.7%	347  65.6%
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.

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 ]

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