Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 65 of 509 for:    melanoma phase III

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00864253
Recruitment Status : Completed
First Posted : March 18, 2009
Results First Posted : June 5, 2014
Last Update Posted : April 26, 2017
Sponsor:
Collaborator:
University of Arizona
Information provided by (Responsible Party):
Celgene

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Malignant Melanoma
Interventions Drug: ABI-007
Drug: Dacarbazine
Enrollment 529
Recruitment Details 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 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).
Arm/Group Title ABI-007 150mg/m^2 Dacarbazine 1000mg/m^2
Hide Arm/Group Description 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 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.
Period Title: Overall Study
Started 264 265
Treated 257 258
Completed 165 [1] 207 [1]
Not Completed 99 58
Reason Not Completed
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
Arm/Group Title ABI-007 150mg/m^2 Dacarbazine Arm B 1000mg/m^2 Total
Hide Arm/Group Description 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 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle. Total of all reporting groups
Overall Number of Baseline Participants 264 265 529
Hide Baseline Analysis Population Description
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.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 264 participants 265 participants 529 participants
62.0
(21 to 85)
64.0
(28 to 87)
63.0
(21 to 87)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 264 participants 265 participants 529 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] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 264 participants 265 participants 529 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]
Measure Description: 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] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 264 participants 265 participants 529 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]
Measure Description: 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] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 264 participants 265 participants 529 participants
M1a 27 21 48
M1b 66 69 135
M1c 171 175 346
[1]
Measure Description: 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] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 264 participants 265 participants 529 participants
V 600 E 65 67 132
Wild Type (mutation negative) 116 108 224
unknown 83 90 173
[1]
Measure Description: 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 Outcome
Title Progression Free Survival (PFS) Based on a Blinded Radiology Assessment of Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines
Hide Description PFS was defined as the time from the randomization date to the start of disease progression or patient death, whichever occurred first. Participants who did not have disease progression or had not died were censored at the last known time that the patient was progression free. In the event of palliative radiotherapy or surgery, they were censored at the last assessment where they were documented to be progression-free prior to the date of radiotherapy or surgery. In follow up, participants who began new anticancer therapy prior to documented progression were censored at the last assessment where they were documented as progression free. Those with two or more missing response assessments prior to a visit with documented disease progression (or death) were censored at the last visit where they were documented to be progression free. RECIST defines progressive disease as a ≥ 20% increase taking as reference the smallest sum of the longest diameters recorded since the treatment began.
Time Frame Response assessment completed every 8 weeks until disease progression for up to 106 weeks; data cut off 30 June 2012
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population = The ITT population consisted of all randomized participants regardless of whether the participant received any study drug or had any efficacy assessments collected.
Arm/Group Title ABI-007 150mg/m^2 Dacarbazine 1000mg/m^2
Hide Arm/Group Description:
ABI-007 150mg/m^2 intravenously over approximately 30 minutes on Days 1, 8 and 15 every 4 weeks
Dacarbazine 1000mg/m^2 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.
Overall Number of Participants Analyzed 264 265
Median (95% Confidence Interval)
Unit of Measure: months
4.8
(3.7 to 5.5)
2.5
(2.0 to 3.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABI-007 150mg/m^2, Dacarbazine 1000mg/m^2
Comments Two hundred fifty-seven (257) patients were to be randomized to each treatment group for a total of 514 patients. This sample size was chosen to provide at least 80% power for the final analysis (with a two-sided type I error of 0.049) to reject the null hypothesis that the ABI 007/dacarbazine hazard ratio (HR) for PFS is equal to 1.0. This sample size calculation was based on estimates of HR = 0.750. Proportional hazards were assumed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.044
Comments An interim safety review was performed by DMC. An alpha spending function was utilized to preserve the overall Type 1 error at 0.050. The spending function allocated alpha of 0.001 and 0.049 to the interim and final analyses of PFS, respectively.
Method Log Rank
Comments The treatment difference was tested using the stratified log-rank test, stratified by metastatic stage, region, and baseline LDH.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.792
Confidence Interval (2-Sided) 95.1%
0.631 to 0.992
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Participant Survival
Hide Description Survival was defined as the time from the date of randomization to the date of death (any cause). Participants were censored at the last known time that they were alive.
Time Frame Up to 38 months; Up to data cut off of 30 June 2012
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population
Arm/Group Title ABI-007 150mg/m^2 Dacarbazine 1000mg/m^2
Hide Arm/Group Description:
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 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.
Overall Number of Participants Analyzed 264 265
Median (95% Confidence Interval)
Unit of Measure: months
12.8
(11.3 to 14.6)
10.7
(9.6 to 12.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABI-007 150mg/m^2, Dacarbazine 1000mg/m^2
Comments For the participant survival, at the time at least 417 events are recorded, this sample size provides at least 80% power with a two-sided Type 1 error of 0.049 to reject the null hypothesis that the ABI-007/dacarbazine hazard ratio is equal to 1.0. This was based on a HR = 0.760. Proportional hazards were assumed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.094
Comments At the time of the final PFS analysis, an interim analysis of survival was reported. The spending function allocated an alpha of 0.001 and 0.049 for the interim and final analysis, respectively, to preserve the overall Type I error at 0.050.
Method Log Rank
Comments The treatment difference was tested using the stratified log-rank test, stratified by metastatic stage, region, and baseline LDH.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.831
Confidence Interval (2-Sided) 99.9%
0.578 to 1.196
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Summary of Treatment-emergent Adverse Events (AEs)
Hide Description

A Treatment Emergent AE (TEAE) was any AE that began or worsened after the start of the study drug through 30 days after the last dose of study drug or end of study whichever is later. A treatment related toxicity was one considered by the investigator to be possibly, probably or definitely related to study drug. AE’s were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V 3.0 criteria and the following scale:

Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life threatening, and Grade 5 = Death A SAE is any untoward medical occurrence at any dose that is fatal or life threatening, results in persistent or significant disability or incapacity; requires prolonged hospitalizations; is a congenital anomaly birth defect in the offspring of a patient, and conditions not included in the above that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.

Time Frame Maximum exposure to study drug was 106 weeks; up to data cut off of 30 June 2012
Hide Outcome Measure Data
Hide Analysis Population Description
Treated Population = The Treated population consisted of all randomized participants who received at least one dose of study drug
Arm/Group Title ABI-007 150mg/m^2 Dacarbazine 1000mg/m^2
Hide Arm/Group Description:
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 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.
Overall Number of Participants Analyzed 257 258
Measure Type: Number
Unit of Measure: participants
≥1 TEAE 255 239
≥1 TEAE related to study drug 250 212
≥1 NCI CTCAE Grade (GR) 3 or above 167 117
≥1 NCI CTCAE GR 3 or above TEAE to study drug 129 71
≥1 TEAE with outcome of death 8 1
≥1 drug related TEAE with outcome of death 2 1
≥1 serious TEAE 62 54
≥1 serious TEAE related to study drug 23 17
≥1 TEAE leading to a dose reduction of study drug 81 51
≥1 related TEAE leading to dose reduction 80 49
≥1 TEAE leading to drug interruption 4 16
≥1 drug related TEAE leading to drug interruption 3 15
≥1 TEAE leading to dose delay of study drug 124 84
≥1 drug related TEAE leading to dose delay 106 77
≥1 TEAE leading to drug discontinuation 59 12
≥1 drug related TEAE leading to drug discontinuing 56 11
4.Secondary Outcome
Title Number of Participants Experiencing Dose Reductions, or Dose Interruptions, or Dose Delays of Study Drug
Hide Description The number of participants with dose reductions, dose interruptions and dose delays that occurred during the treatment period. Dose reductions, interruptions and delays are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.
Time Frame Maximum study drug exposure 106 weeks; data cut off 30 June 2012
Hide Outcome Measure Data
Hide Analysis Population Description
Treated population
Arm/Group Title ABI-007 150mg/m^2 Dacarbazine 1000mg/m^2
Hide Arm/Group Description:
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 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.
Overall Number of Participants Analyzed 257 258
Measure Type: Number
Unit of Measure: participants
Dose Reductions 81 51
Dose Interruptions 6 17
Dose Delay 145 105
5.Secondary Outcome
Title Nadir for the Absolute Neutrophil Count (ANC) Measurements
Hide Description Maximal degree of myelosuppression during study drug dosing was represented by the nadir in ANC measurements over all treatment cycles.
Time Frame Day 1 up to 106 weeks; up to data cut off 30 June 2012
Hide Outcome Measure Data
Hide Analysis Population Description
Treated Population = consisted of all randomized participants who received at least one dose of study drug and with at least one post-baseline central laboratory result were included
Arm/Group Title ABI-007 150mg/m^2 Dacarbazine 1000mg/m^2
Hide Arm/Group Description:
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 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.
Overall Number of Participants Analyzed 253 246
Median (Full Range)
Unit of Measure: 10^9/L
1.50
(0.1 to 20.0)
2.40
(0.0 to 13.2)
6.Secondary Outcome
Title Nadir for White Blood Cells (WBCs) Measurements
Hide Description Maximal degree of myelosuppression was represented by the nadir in white blood cells (WBCs) count measurements over all treatment cycles.
Time Frame Day 1 up to 106 weeks; up to data cut off 30 June 2012
Hide Outcome Measure Data
Hide Analysis Population Description
Treated population = consisted of all randomized participants who received at least one dose of study drug and with at least one post-baseline central laboratory result were included
Arm/Group Title ABI-007 150mg/m^2 Dacarbazine 1000mg/m^2
Hide Arm/Group Description:
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 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.
Overall Number of Participants Analyzed 253 246
Median (Full Range)
Unit of Measure: 10^9/L
3.00
(0.6 to 22.8)
4.10
(0.5 to 14.7)
7.Secondary Outcome
Title Nadir for Platelet Count Measurements.
Hide Description Maximal degree of myelosuppression was represented by the nadir in platelet count measurements over all treatment cycles.
Time Frame Day 1 up to 106 weeks; up to data cut off 30 June 2012
Hide Outcome Measure Data
Hide Analysis Population Description
Treated population = consisted of all randomized participants who received at least one dose of study drug and with at least one post-baseline central laboratory result were included
Arm/Group Title ABI-007 150mg/m^2 Dacarbazine Arm B
Hide Arm/Group Description:
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 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.
Overall Number of Participants Analyzed 252 246
Median (Full Range)
Unit of Measure: 10^9/L
228.5
(112 to 437)
153
(9 to 723)
8.Secondary Outcome
Title Nadir for the Hemoglobin Count Measurements
Hide Description Maximal degree of myelosuppression during study drug dosing was represented by the nadir in hemoglobin count measurements over all treatment cycles.
Time Frame Day 1 up to 106 weeks; up to data cut off 30 June 2012
Hide Outcome Measure Data
Hide Analysis Population Description
Treated population = consisted of all randomized participants who received at least one dose of study drug and with at least one post-baseline central laboratory result were included.
Arm/Group Title ABI-007 150mg/m^2 Dacarbazine 1000mg/m^2
Hide Arm/Group Description:
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 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.
Overall Number of Participants Analyzed 253 246
Median (Full Range)
Unit of Measure: g/L
109.0
(65.0 to 137)
122.0
(65 to 161)
9.Secondary Outcome
Title Pharmacokinetic Parameters
Hide Description [Not Specified]
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
Hide Outcome Measure Data
Hide Analysis Population Description
Patients randomized to receive ABI-007 treatment in Australia, Canada, Europe, United Kingdom and United States had the option to participate in sparse PK sampling in this study. Only 44 participants consented to participate, an insufficient number to support the planned population PK analysis hence these analyses were not performed
Arm/Group Title ABI-007 150mg/m^2 Dacarbazine 1000mg/m^2
Hide Arm/Group Description:
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 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Other Pre-specified Outcome
Title Progression-free Survival (PFS) Based on Investigator Assessment Using RECIST Response Guidelines
Hide Description PFS was defined as the time from the randomization date to the start of disease progression or patient death, whichever occurred first. Participants who did not have disease progression or had not died were censored at the last known time that the patient was progression free. In the event of palliative radiotherapy or surgery, they were censored at the last assessment where they were documented to be progression-free prior to the date of radiotherapy or surgery. In follow up, patients who began new anticancer therapy prior to documented progression were censored at the last assessment where they were documented as progression free. Those with two or more missing response assessments prior to a visit with documented disease progression (or death) were censored at the last visit where they were documented to be progression free.
Time Frame Response assessments completed every 8 weeks until disease progression; up to data cut off 30 June 2012; 38 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title ABI-007 150mg/m^2 Dacarbazine 1000mg/m^2
Hide Arm/Group Description:
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 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.
Overall Number of Participants Analyzed 264 265
Median (95% Confidence Interval)
Unit of Measure: months
3.7
(3.1 to 3.9)
2.1
(1.9 to 2.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABI-007 150mg/m^2, Dacarbazine 1000mg/m^2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.086
Comments [Not Specified]
Method Log Rank
Comments The treatment difference was tested using the stratified log-rank test, stratified by metastatic stage, region, and baseline LDH.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.845
Confidence Interval (2-Sided) 95%
0.696 to 1.025
Estimation Comments [Not Specified]
11.Other Pre-specified Outcome
Title 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
Hide Description RECIST defines complete response (CR): The disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation. All sites must be assessed, including non-measurable sites, such as effusions, or markers. Disappearance of all non-target lesions. The normalization of tumor marker level confirmed at least 4 weeks after initial documentation. Partial response (PR): At least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 4 weeks after initial documentation. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing. As well as persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits.
Time Frame every 8 weeks; up to data cut off 30 June 2012
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title ABI-007 150mg/m^2 Dacarbazine 1000mg/m^2
Hide Arm/Group Description:
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 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.
Overall Number of Participants Analyzed 264 265
Measure Type: Number
Unit of Measure: percentage of participants
Complete Response (CR) 0 0
Partial Response (PR) 15 11
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABI-007 150mg/m^2, Dacarbazine 1000mg/m^2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.239
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Response Rate Ratio
Estimated Value 1.305
Confidence Interval (2-Sided) 95%
0.837 to 2.035
Estimation Comments [Not Specified]
12.Other Pre-specified Outcome
Title 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
Hide Description

Disease control is stable disease (SD) for >=16 weeks + complete response (CR) + partial response (PR). See Outcome #4 for definitions of CR and PR.

RECIST defines SD for target lesions as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions.

Time Frame Response assessment completed every 8 weeks until disease progression; up to data cut-off 30 June 2012
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title ABI-007 150mg/m^2 Dacarbazine 1000mg/m^2
Hide Arm/Group Description:
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 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.
Overall Number of Participants Analyzed 264 265
Measure Type: Number
Unit of Measure: percent of participants
39 27
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABI-007 150mg/m^2, Dacarbazine 1000mg/m^2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Response Rate Ratio
Estimated Value 1.442
Confidence Interval (2-Sided) 95%
1.123 to 1.582
Estimation Comments [Not Specified]
13.Other Pre-specified Outcome
Title Duration of Response (DOR) in Responding Participants
Hide Description Duration of response (DOR) as measured by PFS based on radiological review for participants who achieved an objective confirmed response of CR or PR. DOR was defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or participants death from any cause, whichever occurred first. Participants that did not have progression or had not died were censored at the last known time the participant was progression free. Participants that had initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Complete response (CR) and partial response (PR) are defined in outcome #4. Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.
Time Frame up to data cut off 30 June 2012
Hide Outcome Measure Data
Hide Analysis Population Description
ITT of participants with a confirmed complete or partial overall response
Arm/Group Title ABI-007 150mg/m^2 Dacarbazine 1000mg/m^2
Hide Arm/Group Description:
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 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.
Overall Number of Participants Analyzed 39 30
Median (95% Confidence Interval)
Unit of Measure: months
11.1 [1] 
(7.3 to NA)
16.4
(11.0 to 21.8)
[1]
NA = not estimable (ie., the upper bound of survival curve lies above 0.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABI-007 150mg/m^2, Dacarbazine 1000mg/m^2
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.057
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.201
Confidence Interval (2-Sided) 95%
0.959 to 5.053
Estimation Comments [Not Specified]
Time Frame Any adverse event (AE) that started at any time from the time the signing of the informed consent to 30 days after the last dose of study drug or End of Study was followed and reported; maximum drug exposure 106 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ABI-007 Arm A Dacarbazine Arm B
Hide Arm/Group Description 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 intravenously over approximately 30-60 minutes on Day 1 of each 21 day cycle.
All-Cause Mortality
ABI-007 Arm A Dacarbazine Arm B
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
ABI-007 Arm A Dacarbazine Arm B
Affected / at Risk (%) Affected / at Risk (%)
Total   62/257 (24.12%)   54/258 (20.93%) 
Blood and lymphatic system disorders     
Febrile neutropenia  1  3/257 (1.17%)  1/258 (0.39%) 
Anaemia  1  1/257 (0.39%)  2/258 (0.78%) 
Neutropenia  1  0/257 (0.00%)  1/258 (0.39%) 
Pancytopenia  1  0/257 (0.00%)  1/258 (0.39%) 
Cardiac disorders     
Angina pectoris  1  1/257 (0.39%)  2/258 (0.78%) 
Atrial fibrillation  1  1/257 (0.39%)  2/258 (0.78%) 
Atrial flutter  1  1/257 (0.39%)  0/258 (0.00%) 
Cardio-respiratory arrest  1  1/257 (0.39%)  0/258 (0.00%) 
Acute myocardial infarction  1  0/257 (0.00%)  2/258 (0.78%) 
Palpitations  1  0/257 (0.00%)  1/258 (0.39%) 
Eye disorders     
Maculopathy  1  1/257 (0.39%)  0/258 (0.00%) 
Diplopia  1  0/257 (0.00%)  1/258 (0.39%) 
Gastrointestinal disorders     
Small intestinal obstruction  1  3/257 (1.17%)  1/258 (0.39%) 
Vomiting  1  2/257 (0.78%)  2/258 (0.78%) 
Nausea  1  2/257 (0.78%)  1/258 (0.39%) 
Diarrhoea  1  1/257 (0.39%)  1/258 (0.39%) 
Abdominal pain lower  1  1/257 (0.39%)  0/258 (0.00%) 
Abdominal pain upper  1  1/257 (0.39%)  0/258 (0.00%) 
Ascites  1  1/257 (0.39%)  0/258 (0.00%) 
Ileus  1  1/257 (0.39%)  0/258 (0.00%) 
Colitis  1  0/257 (0.00%)  1/258 (0.39%) 
Pancreatitis  1  0/257 (0.00%)  1/258 (0.39%) 
General disorders     
Pyrexia  1  2/257 (0.78%)  5/258 (1.94%) 
General physical health deterioration  1  1/257 (0.39%)  1/258 (0.39%) 
Death  1  1/257 (0.39%)  0/258 (0.00%) 
Extravasation  1  1/257 (0.39%)  0/258 (0.00%) 
Fatigue  1  1/257 (0.39%)  0/258 (0.00%) 
Implant site thrombosis  1  1/257 (0.39%)  0/258 (0.00%) 
Oedema  1  1/257 (0.39%)  0/258 (0.00%) 
Asthenia  1  0/257 (0.00%)  1/258 (0.39%) 
Non-cardiac chest pain 0 1  1  0/257 (0.00%)  1/258 (0.39%) 
Hepatobiliary disorders     
Cholelithiasis  1  1/257 (0.39%)  0/258 (0.00%) 
Hepatic function abnormal  1  1/257 (0.39%)  0/258 (0.00%) 
Bile duct obstruction  1  0/257 (0.00%)  1/258 (0.39%) 
Immune system disorders     
Hypersensitivity  1  0/257 (0.00%)  2/258 (0.78%) 
Infections and infestations     
Pneumonia  1  4/257 (1.56%)  1/258 (0.39%) 
Cellulitis  1  3/257 (1.17%)  4/258 (1.55%) 
Erysipelas  1  3/257 (1.17%)  0/258 (0.00%) 
Urinary tract infection  1  3/257 (1.17%)  0/258 (0.00%) 
Device related infection  1  1/257 (0.39%)  1/258 (0.39%) 
Neutropenic sepsis  1  1/257 (0.39%)  1/258 (0.39%) 
Sepsis  1  1/257 (0.39%)  1/258 (0.39%) 
Anal abscess  1  1/257 (0.39%)  0/258 (0.00%) 
Bronchitis  1  1/257 (0.39%)  0/258 (0.00%) 
Respiratory tract infection  1  1/257 (0.39%)  0/258 (0.00%) 
Septic shock  1  1/257 (0.39%)  0/258 (0.00%) 
Skin infection  1  1/257 (0.39%)  0/258 (0.00%) 
Streptococcal bacteraemia  1  1/257 (0.39%)  0/258 (0.00%) 
Swine influenza  1  1/257 (0.39%)  0/258 (0.00%) 
Wound infection  1  1/257 (0.39%)  0/258 (0.00%) 
Catheter related infection  1  0/257 (0.00%)  1/258 (0.39%) 
Clostridium difficile colitis  1  0/257 (0.00%)  1/258 (0.39%) 
Escherichia bacteraemia  1  0/257 (0.00%)  1/258 (0.39%) 
Infected skin ulcer  1  0/257 (0.00%)  1/258 (0.39%) 
Osteomyelitis  1  0/257 (0.00%)  1/258 (0.39%) 
Injury, poisoning and procedural complications     
Fall  1  1/257 (0.39%)  0/258 (0.00%) 
Muscle strain  1  0/257 (0.00%)  1/258 (0.39%) 
Traumatic brain injury  1  0/257 (0.00%)  1/258 (0.39%) 
Metabolism and nutrition disorders     
Dehydration  1  1/257 (0.39%)  0/258 (0.00%) 
Hypocalcaemia  1  1/257 (0.39%)  0/258 (0.00%) 
Hypokalaemia  1  1/257 (0.39%)  0/258 (0.00%) 
Hypomagnesaemia  1  1/257 (0.39%)  0/258 (0.00%) 
Musculoskeletal and connective tissue disorders     
Pathological fracture  1  1/257 (0.39%)  1/258 (0.39%) 
Lumbar spinal stenosis  1  1/257 (0.39%)  0/258 (0.00%) 
Pain in extremity  1  1/257 (0.39%)  0/258 (0.00%) 
Arthralgia  1  0/257 (0.00%)  1/258 (0.39%) 
Back pain  1  0/257 (0.00%)  1/258 (0.39%) 
Osteoporotic fracture  1  0/257 (0.00%)  1/258 (0.39%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Haemorrhagic tumour necrosis  1  1/257 (0.39%)  0/258 (0.00%) 
Tumour pain  1  0/257 (0.00%)  2/258 (0.78%) 
Nervous system disorders     
Peripheral motor neuropathy  1  2/257 (0.78%)  0/258 (0.00%) 
Peripheral sensory neuropathy  1  2/257 (0.78%)  0/258 (0.00%) 
Cerebrovascular accident  1  1/257 (0.39%)  1/258 (0.39%) 
Syncope  1  1/257 (0.39%)  1/258 (0.39%) 
Aphasia  1  1/257 (0.39%)  0/258 (0.00%) 
Cerebral haematoma  1  1/257 (0.39%)  0/258 (0.00%) 
Dizziness  1  1/257 (0.39%)  0/258 (0.00%) 
Haemorrhage intracranial  1  1/257 (0.39%)  0/258 (0.00%) 
Neuropathy peripheral  1  1/257 (0.39%)  0/258 (0.00%) 
Subarachnoid haemorrhage  1  1/257 (0.39%)  0/258 (0.00%) 
Transient ischaemic attack  1  1/257 (0.39%)  0/258 (0.00%) 
Ataxia  1  0/257 (0.00%)  1/258 (0.39%) 
Cerebrovascular stenosis  1  0/257 (0.00%)  1/258 (0.39%) 
Haemorrhagic stroke  1  0/257 (0.00%)  1/258 (0.39%) 
Hemiparesis  1  0/257 (0.00%)  1/258 (0.39%) 
Monoplegia  1  0/257 (0.00%)  1/258 (0.39%) 
Presyncope  1  0/257 (0.00%)  1/258 (0.39%) 
Spinal cord compression  1  0/257 (0.00%)  1/258 (0.39%) 
Psychiatric disorders     
Anxiety  1  1/257 (0.39%)  0/258 (0.00%) 
Completed suicide  1  1/257 (0.39%)  0/258 (0.00%) 
Renal and urinary disorders     
Haematuria  1  1/257 (0.39%)  0/258 (0.00%) 
Renal failure acute  1  1/257 (0.39%)  0/258 (0.00%) 
Urinary retention  1  1/257 (0.39%)  0/258 (0.00%) 
Renal pain  1  0/257 (0.00%)  1/258 (0.39%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  1/257 (0.39%)  1/258 (0.39%) 
Pulmonary embolism  1  1/257 (0.39%)  1/258 (0.39%) 
Haemoptysis  1  0/257 (0.00%)  2/258 (0.78%) 
Skin and subcutaneous tissue disorders     
Urticaria  1  0/257 (0.00%)  1/258 (0.39%) 
Vascular disorders     
Deep vein thrombosis  1  1/257 (0.39%)  0/258 (0.00%) 
Hypotension  1  1/257 (0.39%)  0/258 (0.00%) 
Orthostatic hypotension  1  1/257 (0.39%)  0/258 (0.00%) 
Venous thrombosis  1  0/257 (0.00%)  1/258 (0.39%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 12.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ABI-007 Arm A Dacarbazine Arm B
Affected / at Risk (%) Affected / at Risk (%)
Total   253/257 (98.44%)   232/258 (89.92%) 
Blood and lymphatic system disorders     
Neutropenia  1  66/257 (25.68%)  63/258 (24.42%) 
Anaemia  1  39/257 (15.18%)  28/258 (10.85%) 
Leukopenia  1  31/257 (12.06%)  23/258 (8.91%) 
Thrombocytopenia  1  1/257 (0.39%)  43/258 (16.67%) 
Eye disorders     
Vision blurred  1  19/257 (7.39%)  6/258 (2.33%) 
Lacrimation increased  1  17/257 (6.61%)  4/258 (1.55%) 
Gastrointestinal disorders     
Nausea  1  104/257 (40.47%)  130/258 (50.39%) 
Diarrhoea  1  103/257 (40.08%)  45/258 (17.44%) 
Constipation  1  83/257 (32.30%)  89/258 (34.50%) 
Vomiting  1  53/257 (20.62%)  56/258 (21.71%) 
Abdominal pain  1  34/257 (13.23%)  28/258 (10.85%) 
Dyspepsia  1  24/257 (9.34%)  20/258 (7.75%) 
Stomatitis  1  18/257 (7.00%)  8/258 (3.10%) 
Abdominal pain upper  1  17/257 (6.61%)  14/258 (5.43%) 
General disorders     
Fatigue  1  134/257 (52.14%)  110/258 (42.64%) 
Oedema peripheral  1  54/257 (21.01%)  24/258 (9.30%) 
Asthenia  1  39/257 (15.18%)  28/258 (10.85%) 
Pyrexia  1  32/257 (12.45%)  30/258 (11.63%) 
Mucosal inflammation  1  20/257 (7.78%)  13/258 (5.04%) 
Pain  1  20/257 (7.78%)  10/258 (3.88%) 
Chills  1  12/257 (4.67%)  15/258 (5.81%) 
Infusion site pain  1  2/257 (0.78%)  13/258 (5.04%) 
Infections and infestations     
Upper respiratory tract infection  1  18/257 (7.00%)  13/258 (5.04%) 
Nasopharyngitis  1  14/257 (5.45%)  10/258 (3.88%) 
Investigations     
Weight decreased  1  16/257 (6.23%)  10/258 (3.88%) 
Metabolism and nutrition disorders     
Decreased appetite  1  68/257 (26.46%)  52/258 (20.16%) 
Hypokalaemia  1  13/257 (5.06%)  10/258 (3.88%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  48/257 (18.68%)  24/258 (9.30%) 
Myalgia  1  44/257 (17.12%)  10/258 (3.88%) 
Pain in extremity  1  33/257 (12.84%)  20/258 (7.75%) 
Back pain  1  24/257 (9.34%)  26/258 (10.08%) 
Muscular weakness  1  16/257 (6.23%)  5/258 (1.94%) 
Musculoskeletal pain  1  16/257 (6.23%)  16/258 (6.20%) 
Nervous system disorders     
Neuropathy peripheral  1  98/257 (38.13%)  6/258 (2.33%) 
Dysgeusia  1  62/257 (24.12%)  24/258 (9.30%) 
Peripheral sensory neuropathy  1  52/257 (20.23%)  9/258 (3.49%) 
Headache  1  42/257 (16.34%)  38/258 (14.73%) 
Paraesthesia  1  41/257 (15.95%)  8/258 (3.10%) 
Dizziness  1  32/257 (12.45%)  30/258 (11.63%) 
Psychiatric disorders     
Insomnia  1  42/257 (16.34%)  31/258 (12.02%) 
Anxiety  1  16/257 (6.23%)  19/258 (7.36%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  59/257 (22.96%)  33/258 (12.79%) 
Dyspnoea  1  39/257 (15.18%)  38/258 (14.73%) 
Epistaxis  1  34/257 (13.23%)  5/258 (1.94%) 
Oropharyngeal pain  1  17/257 (6.61%)  9/258 (3.49%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  177/257 (68.87%)  9/258 (3.49%) 
Rash  1  72/257 (28.02%)  18/258 (6.98%) 
Nail disorder  1  52/257 (20.23%)  2/258 (0.78%) 
Pruritus  1  31/257 (12.06%)  17/258 (6.59%) 
Dry skin  1  24/257 (9.34%)  5/258 (1.94%) 
Erythema  1  16/257 (6.23%)  5/258 (1.94%) 
Photosensitivity reaction  1  3/257 (1.17%)  13/258 (5.04%) 
Vascular disorders     
Flushing  1  8/257 (3.11%)  16/258 (6.20%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 12.1
Participation in the PK sampling for participants randomized to the ABI-007 arm was optional; too few samples were available to support the analysis
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.
Institution may publish the results of its findings if a multicenter publication is not forthcoming within 18 months after study completion. Institution shall provide Celgene with a copy of the papers prior to submission; Celgene shall complete its review within 60 days. Institution shall review comments from Celgene. Upon Celgene's request, proposed publication will be delayed up to 60 additional days to allow Celgene to secure adequate intellectual property protection of patentable material.
Results Point of Contact
Name/Title: Anne McClain
Organization: Celgene Corporation
Phone: 888-260-1599
Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT00864253     History of Changes
Other Study ID Numbers: CA033
First Submitted: March 16, 2009
First Posted: March 18, 2009
Results First Submitted: April 16, 2014
Results First Posted: June 5, 2014
Last Update Posted: April 26, 2017