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Trial record 91 of 510 for:    melanoma phase III

A Study of Tasisulam-sodium Versus Paclitaxel as Treatment for Metastatic Melanoma (SUMMIT-1)

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: NCT01006252
Recruitment Status : Terminated (More possibly treatment-related deaths on tasisulam-sodium arm.)
First Posted : November 2, 2009
Results First Posted : July 17, 2018
Last Update Posted : July 17, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Melanoma
Interventions Drug: Tasisulam-sodium
Drug: Paclitaxel
Enrollment 336
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Tasisulam-sodium Paclitaxel
Hide Arm/Group Description Individualized tasisulam-sodium dose was dependent on participant's height, weight, and gender. Dose was adjusted based on laboratory parameters. Treatment was administered intravenously on Day 1 of a 28-day cycle, until disease progression. Paclitaxel 80 mg/m^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle, until disease progression
Period Title: Overall Study
Started 168 168
Received Treatment 164 161
Completed 168 168
Not Completed 0 0
Arm/Group Title Tasisulam-sodium Paclitaxel Total
Hide Arm/Group Description Individualized tasisulam-sodium dose was dependent on participant's height, weight, and gender. Dose was adjusted based on laboratory parameters. Treatment was administered intravenously on Day 1 of a 28-day cycle, until disease progression. Paclitaxel 80 mg/m^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle, until disease progression Total of all reporting groups
Overall Number of Baseline Participants 168 168 336
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 168 participants 168 participants 336 participants
58.30  (13.20) 59.44  (13.43) 58.87  (13.31)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 168 participants 168 participants 336 participants
Female
65
  38.7%
63
  37.5%
128
  38.1%
Male
103
  61.3%
105
  62.5%
208
  61.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 168 participants 168 participants 336 participants
Hispanic or Latino
1
   0.6%
4
   2.4%
5
   1.5%
Not Hispanic or Latino
84
  50.0%
75
  44.6%
159
  47.3%
Unknown or Not Reported
83
  49.4%
89
  53.0%
172
  51.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 168 participants 168 participants 336 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
10
   6.0%
5
   3.0%
15
   4.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
158
  94.0%
162
  96.4%
320
  95.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
   0.6%
1
   0.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 168 participants 168 participants 336 participants
United States
40
  23.8%
50
  29.8%
90
  26.8%
Finland
1
   0.6%
2
   1.2%
3
   0.9%
Spain
3
   1.8%
7
   4.2%
10
   3.0%
Austria
5
   3.0%
3
   1.8%
8
   2.4%
Israel
3
   1.8%
3
   1.8%
6
   1.8%
United Kingdom
8
   4.8%
1
   0.6%
9
   2.7%
Italy
8
   4.8%
11
   6.5%
19
   5.7%
France
32
  19.0%
26
  15.5%
58
  17.3%
Canada
4
   2.4%
8
   4.8%
12
   3.6%
Poland
7
   4.2%
6
   3.6%
13
   3.9%
Belgium
7
   4.2%
6
   3.6%
13
   3.9%
Australia
1
   0.6%
5
   3.0%
6
   1.8%
Norway
5
   3.0%
5
   3.0%
10
   3.0%
Germany
32
  19.0%
28
  16.7%
60
  17.9%
Sweden
3
   1.8%
3
   1.8%
6
   1.8%
South Korea
9
   5.4%
4
   2.4%
13
   3.9%
1.Primary Outcome
Title Overall Survival (OS)
Hide Description OS is duration from enrollment to death; OS censored for participants who were alive at last contact.
Time Frame Randomization to date of death from any cause (assessed at every cycle and every 60 days following treatment discontinuation) up to 14.32 months
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) analysis population included all participants randomized to treatment.
Arm/Group Title Tasisulam-sodium Paclitaxel
Hide Arm/Group Description:
Individualized tasisulam-sodium dose was dependent on participant's height, weight, and gender. Dose was adjusted based on laboratory parameters. Treatment was administered intravenously on Day 1 of a 28-day cycle, until disease progression.
Paclitaxel 80 mg/m^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle, until disease progression.
Overall Number of Participants Analyzed 168 168
Median (95% Confidence Interval)
Unit of Measure: months
6.77
(5.88 to 8.28)
9.36 [1] 
(6.90 to NA)
[1]
The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tasisulam-sodium, Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.121
Comments Statistical significance was assessed at an alpha level of 0.05.
Method Stratified log rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.23
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS is time from date of first dose to first observation of disease progression (PD); PD=20% increase in sum of the longest diameter of target lesions, or death from any cause.
Time Frame Randomization to date of objectively determined PD, or death from any cause (assessed at every cycle and every 60 days following treatment discontinuation) up to 13.70 months
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) analysis population included all participants randomized to treatment.
Arm/Group Title Tasisulam-sodium Paclitaxel
Hide Arm/Group Description:
Individualized tasisulam-sodium dose was dependent on participant's height, weight, and gender. Dose was adjusted based on laboratory parameters. Treatment was administered intravenously on Day 1 of a 28-day cycle, until disease progression.
Paclitaxel 80 mg/m^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle, until disease progression
Overall Number of Participants Analyzed 168 168
Median (95% Confidence Interval)
Unit of Measure: months
1.94
(1.87 to 2.04)
2.14
(1.91 to 2.96)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tasisulam-sodium, Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.048
Comments Statistical significance was assessed at an alpha level of 0.05.
Method Stratified log rank
Comments Analysis adjusted for Baseline Lactate Dehydrogenase (LDH); Disease Stage; Sex; Previous Single Agent Immunotherapy Treatment; Age Group
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.30
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Randomized Participants Having a Confirmed Best Response of Partial Response (PR) or Complete Response (CR)
Hide Description Response Evaluation Criteria In Solid Tumors (RECIST) criteria: CR=disappearance of all target lesions; PR=30% decrease in sum of longest diameter of target lesions; Progressive disease (PD)=20% increase in sum of the longest diameter of target lesions.
Time Frame First date RECIST criteria met for CR or PR (whichever occurred first) until first date of documented PD, or death from any cause (assessed every other cycle) up to 13.70 months
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) analysis population included all participants randomized to treatment.
Arm/Group Title Tasisulam-sodium Paclitaxel
Hide Arm/Group Description:
Individualized tasisulam-sodium dose was dependent on participant's height, weight, and gender. Dose was adjusted based on laboratory parameters. Treatment was administered intravenously on Day 1 of a 28-day cycle, until disease progression.
Paclitaxel 80 mg/m^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle, until disease progression
Overall Number of Participants Analyzed 168 168
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
CR
0
(0 to 0)
0
(0 to 0)
PR
3.0
(0.4 to 5.5)
4.8
(1.5 to 8.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tasisulam-sodium, Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.396
Comments Statistical significance was assessed at an alpha level of 0.05.
Method Unadjusted normal distribution
Comments Unadjusted normal-distribution approximation for the difference in rates
4.Secondary Outcome
Title Duration of Response (DoR) for Participants Having an Objective Response of Partial Response (PR) or Complete Response (CR)
Hide Description Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: CR=disappearance of all target lesions; PR=30% decrease in sum of longest diameter of target lesions; Progressive disease (PD)=20% increase in sum of the longest diameter of target lesions. Analysis was adjusted for Baseline Lactate Dehydrogenase (LDH); Disease Stage; Sex; Previous Single Agent Immunotherapy Treatment; Age Group. Due to limited number of responses for either treatment arm, DoR analysis was not performed.
Time Frame First date RECIST criteria met for CR or PR (whichever occurred first) until first date of documented PD, or death from any cause (assessed every other cycle) up to 13.70 months
Hide Outcome Measure Data
Hide Analysis Population Description
Zero participants analyzed. Duration of Response for CR and PR data was not collected for analysis per study report.
Arm/Group Title Tasisulam-sodium Paclitaxel
Hide Arm/Group Description:
Individualized tasisulam-sodium dose was dependent on participant's height, weight, and gender. Dose was adjusted based on laboratory parameters. Treatment was administered intravenously on Day 1 of a 28-day cycle, until disease progression.
Paclitaxel 80 mg/m^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle, until disease progression
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Percentage of Randomized Participants Having a Confirmed Best Overall Response of Partial Response (PR) or Complete Response (CR) Plus Participants With an Overall Response of Stable Disease (SD)
Hide Description Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: CR=disappearance of all target lesions; PR=30% decrease in sum of longest diameter of target lesions; SD=small changes that do not meet above criteria; PD=20% increase in sum of the longest diameter of target lesions.
Time Frame First date RECIST criteria met for CR, PR, or SD until first date of documented progressive disease (PD), or death from any cause (assessed every other cycle) up to 13.70 months
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) analysis population included all participants randomized to treatment.
Arm/Group Title Tasisulam-sodium Paclitaxel
Hide Arm/Group Description:
Individualized tasisulam-sodium dose was dependent on participant's height, weight, and gender. Dose was adjusted based on laboratory parameters. Treatment was administered intravenously on Day 1 of a 28-day cycle, until disease progression.
Paclitaxel 80 mg/m^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle, until disease progression
Overall Number of Participants Analyzed 168 168
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
30.4
(23.4 to 37.3)
33.9
(26.8 to 41.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tasisulam-sodium, Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.483
Comments Statistical significance was assessed at an alpha level of 0.05.
Method Unadjusted normal distribution
Comments Unadjusted normal-distribution approximation for the difference in rates.
6.Secondary Outcome
Title Time to Deterioration in the Functional Assessment of Cancer Therapy-Melanoma Trial Outcome Index (FACT-M TOI) Score
Hide Description FACT-M measures domains of health-related quality of life (HR-QoL): physical well-being, social/family well-being, emotional well-being, functional well-being, and additional concerns of melanoma. FACT-M TOI is the sum of FACT-M physical well-being, functional well-being, and melanoma subscales. Scores range from 0 to 120; Higher scores=better quality of life (QoL). FACT-M TOI score deterioration was defined as time from randomization to a minimally important difference in TOI score or death.
Time Frame Randomization to first date of deterioration in FACT-M TOI, or death from any cause (assessed every cycle and up to 30 days following treatment discontinuation) up to 13.21 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all randomized participants who had baseline and at least 1 post-baseline measurement.
Arm/Group Title Tasisulam-sodium Paclitaxel
Hide Arm/Group Description:
Individualized tasisulam-sodium dose was dependent on participant's height, weight, and gender. Dose was adjusted based on laboratory parameters. Treatment was administered intravenously on Day 1 of a 28-day cycle, until disease progression.
Paclitaxel 80 mg/m^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle, until disease progression
Overall Number of Participants Analyzed 136 141
Median (95% Confidence Interval)
Unit of Measure: months
2.96
(2.30 to 3.71)
3.52
(2.99 to 4.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tasisulam-sodium, Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.505
Comments Statistical significance was assessed at an alpha level of 0.05.
Method Stratified log rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline at Cycle 2 in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) up to 30 Days Following Treatment Discontinuation
Hide Description FACT-M measures domains of health-related quality of life (HR-QoL): physical well-being, social/family well-being, emotional well-being, functional well-being, and additional concerns of melanoma. Total scores range from 0 to 172; Higher scores=better HR-QoL. Least Squares (LS) Mean value was adjusted for treatment group, cycle, treatment-by-cycle interaction, age, Eastern Cooperative Oncology Group (ECOG) performance status, stage of disease at study entry, and best response to previous chemotherapy.
Time Frame Baseline at Cycle 2, up to 30 days following treatment discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all randomized participants who had baseline and at least 1 post-baseline measurement.
Arm/Group Title Tasisulam-sodium Paclitaxel
Hide Arm/Group Description:
Individualized tasisulam-sodium dose was dependent on participant's height, weight, and gender. Dose was adjusted based on laboratory parameters. Treatment was administered intravenously on Day 1 of a 28-day cycle, until disease progression.
Paclitaxel 80 mg/m^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle, until disease progression
Overall Number of Participants Analyzed 136 141
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.81  (2.38) -1.07  (2.40)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tasisulam-sodium, Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.902
Comments P-value given for Overall Main Treatment Effect from the repeated measure model where time was a class variable. Statistical significance was assessed at an alpha level of 0.05.
Method Mixed Model Repeated Measures (MMRM)
Comments MMRM analyses limited to first 4 cycles due to sparse data; data from 30-day follow-up visit coded to first cycle after last on-treatment cycle.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tasisulam-sodium, Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.970
Comments P-value given for Treatment-By-Cycle Interaction from the repeated measure model where time was a class variable. Statistical significance was assessed at an alpha level of 0.05.
Method Mixed Model Repeated Measures (MMRM)
Comments MMRM analyses limited to first 4 cycles due to sparse data; data from 30-day follow-up visit coded to first cycle after last on-treatment cycle.
8.Secondary Outcome
Title Change From Baseline at Cycle 3 in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) up to 30 Days Following Treatment Discontinuation
Hide Description FACT-M measures domains of health-related quality of life (HR-QoL): physical well-being, social/family well-being, emotional well-being, functional well-being, and additional concerns of melanoma. Total scores range from 0 to 172; Higher scores=better HR-QoL. Least Squares (LS) Mean value was adjusted for treatment group, cycle, treatment-by-cycle interaction, age, Eastern Cooperative Oncology Group (ECOG) performance status, stage of disease at study entry, and best response to previous chemotherapy.
Time Frame Baseline at Cycle 3, up to 30 days following treatment discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all randomized participants who had baseline and at least 1 post-baseline measurement.
Arm/Group Title Tasisulam-sodium Paclitaxel
Hide Arm/Group Description:
Individualized tasisulam-sodium dose was dependent on participant's height, weight, and gender. Dose was adjusted based on laboratory parameters. Treatment was administered intravenously on Day 1 of a 28-day cycle until disease progression.
Paclitaxel 80 mg/m^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle until disease progression.
Overall Number of Participants Analyzed 117 118
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-4.06  (2.47) -4.69  (2.51)
9.Secondary Outcome
Title Change From Baseline at Cycle 4 in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) up to 30 Days Following Treatment Discontinuation
Hide Description FACT-M measures domains of health-related quality of life (HR-QoL): physical well-being, social/family well-being, emotional well-being, functional well-being, and additional concerns of melanoma. Total scores range from 0 to 172; Higher scores=better HR-QoL. Least Squares (LS) Mean value was adjusted for treatment group, cycle, treatment-by-cycle interaction, age, Eastern Cooperative Oncology Group (ECOG) performance status, stage of disease at study entry, and best response to previous chemotherapy.
Time Frame Baseline at Cycle 4, up to 30 days following treatment discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all randomized participants who had baseline and at least 1 post-baseline measurement.
Arm/Group Title Tasisulam-sodium Paclitaxel
Hide Arm/Group Description:
Individualized tasisulam-sodium dose was dependent on participant's height, weight, and gender. Dose was adjusted based on laboratory parameters. Treatment was administered intravenously on Day 1 of a 28-day cycle, until disease progression.
Paclitaxel 80 mg/m^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle, until disease progression.
Overall Number of Participants Analyzed 46 50
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.86  (2.66) -2.98  (2.69)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tasisulam-sodium, Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.902
Comments P-value given for Overall Main Treatment Effect from the repeated measure model where time was a class variable. Statistical significance was assessed at an alpha level of 0.05.
Method Mixed Model Repeated Measures (MMRM)
Comments MMRM analyses limited to first 4 cycles due to sparse data; data from 30-day follow-up visit coded to first cycle after last on-treatment cycle.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tasisulam-sodium, Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.970
Comments P-value given for Overall Treatment-By-Cycle Interaction from the repeated measure model where time was a class variable. Statistical significance was assessed at an alpha level of 0.05.
Method Mixed Model Repeated Measures (MMRM)
Comments MMRM analyses limited to first 4 cycles due to sparse data; data from 30-day follow-up visit coded to first cycle after last on-treatment cycle.
10.Secondary Outcome
Title Change From Baseline at Cycle 2 in EuroQol-5 Dimensions (EQ-5D) up to 30 Days Following Treatment Discontinuation
Hide Description EQ-5D consists of 5 items that assess participant's overall health. Participants choose 1 of 3 options that best describe the status of each item. EQ-5D United Kingdom (UK)-based index scores range from -0.59 (worst health) to 1.0 (1.0=perfect health; Positive change from baseline=health improvement). Least Squares (LS) Mean value was adjusted for treatment group, cycle, treatment-by-cycle interaction, age, Eastern Cooperative Oncology Group (ECOG) performance status, stage of disease at study entry, and best response to previous chemotherapy.
Time Frame Baseline at Cycle 2, up to 30 days following treatment discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all randomized participants who had baseline and at least 1 post-baseline measurement.
Arm/Group Title Tasisulam-sodium Paclitaxel
Hide Arm/Group Description:
Individualized tasisulam-sodium dose was dependent on participant's height, weight, and gender. Dose was adjusted based on laboratory parameters. Treatment was administered intravenously on Day 1 of a 28-day cycle, until disease progression.
Paclitaxel 80 mg/m^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle, until disease progression
Overall Number of Participants Analyzed 133 134
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.01  (0.03) -0.00  (0.03)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tasisulam-sodium, Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.547
Comments P-value given for Main Treatment Effect from the repeated measure model where time was a class variable. Statistical significance was assessed at an alpha level of 0.05.
Method Mixed Model Repeated Measures (MMRM)
Comments MMRM analyses limited to first 4 cycles due to sparse data; data from 30-day follow-up visit coded to first cycle after last on-treatment cycle.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tasisulam-sodium, Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.414
Comments P-value given for Treatment-By-Cycle Interaction from the repeated measure model where time was a class variable. Statistical significance was assessed at an alpha level of 0.05.
Method Mixed Model Repeated Measures (MMRM)
Comments MMRM analyses limited to first 4 cycles due to sparse data; data from 30-day follow-up visit coded to first cycle after last on-treatment cycle.
11.Secondary Outcome
Title Change From Baseline at Cycle 3 in EuroQol-5 Dimensions (EQ-5D) up to 30 Days Following Treatment Discontinuation
Hide Description EQ-5D consists of 5 items that assess participant's overall health. Participants choose 1 of 3 options that best describe status of each item. EQ-5D United Kingdom (UK)-based index scores range from -0.59 (worst health) to 1.0 (1.0=perfect health; Positive change from baseline=health improvement). Least Squares (LS) Mean value was adjusted for treatment group, cycle, treatment-by-cycle interaction, age, Eastern Cooperative Oncology Group (ECOG) performance status, stage of disease at study entry, and best response to previous chemotherapy.
Time Frame Baseline at Cycle 3, up to 30 days following treatment discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all randomized participants who had baseline and at least 1 post-baseline measurement.
Arm/Group Title Tasisulam-sodium Paclitaxel
Hide Arm/Group Description:
Individualized tasisulam-sodium dose was dependent on participant's height, weight, and gender. Dose was adjusted based on laboratory parameters. Treatment was administered intravenously on Day 1 of a 28-day cycle, until disease progression.
Paclitaxel 80 mg/m^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle, until disease progression.
Overall Number of Participants Analyzed 80 77
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.01  (0.03) -0.06  (0.03)
12.Secondary Outcome
Title Change From Baseline at Cycle 4 Baseline in EuroQol-5 Dimensions (EQ-5D) up to 30 Days Following Treatment Discontinuation
Hide Description EQ-5D consists of 5 items that assess participant's overall health. Participants choose 1 of 3 options that best describe status of each item. EQ-5D United Kingdom (UK)-based index scores range from -0.59 (worst health) to 1.0 (1.0=perfect health; Positive change from baseline=health improvement). Least Squares (LS) Mean value was adjusted for treatment group, cycle, treatment-by-cycle interaction, age, Eastern Cooperative Oncology Group (ECOG) performance status, stage of disease at study entry, and best response to previous chemotherapy.
Time Frame Baseline at Cycle 4, up to 30 days after treatment discontinuation
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all randomized participants who had baseline and at least 1 post-baseline measurement.
Arm/Group Title Tasisulam-sodium Paclitaxel
Hide Arm/Group Description:
Individualized tasisulam-sodium dose was dependent on participant's height, weight, and gender. Dose was adjusted based on laboratory parameters. Treatment was administered intravenously on Day 1 of a 28-day cycle, until disease progression.
Paclitaxel 80 mg/m^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle, until disease progression.
Overall Number of Participants Analyzed 42 43
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.05  (0.04) -0.05  (0.04)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tasisulam-sodium, Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.547
Comments P-value given for Main Treatment Effect from the repeated measure model where time was a class variable. Statistical significance was assessed at an alpha level of 0.05.
Method Mixed Model Repeated Measures (MMRM)
Comments MMRM analyses limited to first 4 cycles due to sparse data; data from 30-day follow-up visit coded to first cycle after last on-treatment cycle.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Tasisulam-sodium, Paclitaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.414
Comments P-value given for Treatment-By-Cycle Interaction from the repeated measure model where time was a class variable. Statistical significance was assessed at an alpha level of 0.05.
Method Mixed Model Repeated Measures (MMRM)
Comments MMRM analyses limited to first 4 cycles due to sparse data; data from 30-day follow-up visit coded to first cycle after last on-treatment cycle.
13.Secondary Outcome
Title Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) During Cycle 1
Hide Description [Not Specified]
Time Frame After drug infusion in Cycle 1 (5 samples drawn over the 28-day cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received at least 1 dose of study drug for whom PK data were available. PK analysis were only performed on Tasisulam per protocol.
Arm/Group Title Tasisulam
Hide Arm/Group Description:
Dose was adjusted based on participant laboratory parameters and lean body weight; administered intravenously every 28 days until disease progression, or other criteria for participant discontinuation were met.
Overall Number of Participants Analyzed 162
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: microgram per milliliter (µg/mL)
375
(14.8%)
14.Secondary Outcome
Title Pharmacokinetics: Maximum Plasma Concentration (Cmax) During Cycle 2
Hide Description [Not Specified]
Time Frame After drug infusion in Cycle 2 (2 samples drawn over the 28-day cycle)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population included all participants who received at least 2 doses of study drug for whom pharmacokinetic data were available. PK analysis were only performed on Tasisulam per protocol.
Arm/Group Title Tasisulam
Hide Arm/Group Description:
Dose was adjusted based on participant laboratory parameters and lean body weight; administered intravenously every 28 days until disease progression, or other criteria for participant discontinuation were met.
Overall Number of Participants Analyzed 129
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: µg/mL
361
(16.8%)
Time Frame [Not Specified]
Adverse Event Reporting Description All randomized participants who received treatment.
 
Arm/Group Title Tasisulam-sodium Paclitaxel
Hide Arm/Group Description Individualized tasisulam-sodium dose was dependent on participant's height, weight, and gender. Dose was adjusted based on laboratory parameters. Treatment was administered intravenously on Day 1 of a 28-day cycle, until disease progression. Paclitaxel 80 mg/m^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle, until disease progression
All-Cause Mortality
Tasisulam-sodium Paclitaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Tasisulam-sodium Paclitaxel
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   53/164 (32.32%)      44/161 (27.33%)    
Blood and lymphatic system disorders     
Anaemia  1  5/164 (3.05%)  5 0/161 (0.00%)  0
Febrile neutropenia  1  4/164 (2.44%)  4 1/161 (0.62%)  1
Granulocytopenia  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Haemorrhagic diathesis  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Leukopenia  1  5/164 (3.05%)  5 0/161 (0.00%)  0
Neutropenia  1  6/164 (3.66%)  6 2/161 (1.24%)  2
Thrombocytopenia  1  18/164 (10.98%)  19 1/161 (0.62%)  1
Cardiac disorders     
Angina pectoris  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Arrhythmia  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Atrial fibrillation  1  2/164 (1.22%)  2 1/161 (0.62%)  1
Atrioventricular block  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Bradycardia  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Cardiac failure congestive  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Cardiac tamponade  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Cardiopulmonary failure  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Mitral valve incompetence  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Myocardial infarction  1  2/164 (1.22%)  2 0/161 (0.00%)  0
Tachyarrhythmia  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  1  1/164 (0.61%)  1 3/161 (1.86%)  3
Anal haemorrhage  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Colitis  1  3/164 (1.83%)  3 0/161 (0.00%)  0
Diarrhoea  1  2/164 (1.22%)  2 0/161 (0.00%)  0
Gastric haemorrhage  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Gastric ulcer  1  1/164 (0.61%)  1 1/161 (0.62%)  1
Gastrointestinal fistula  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Gastrointestinal haemorrhage  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Haemorrhoidal haemorrhage  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Ileus  1  2/164 (1.22%)  2 1/161 (0.62%)  1
Nausea  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Pancreatitis  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Small intestinal obstruction  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Vomiting  1  1/164 (0.61%)  1 2/161 (1.24%)  2
General disorders     
Asthenia  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Chest pain  1  2/164 (1.22%)  2 0/161 (0.00%)  0
Chills  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Discomfort  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Fatigue  1  0/164 (0.00%)  0 2/161 (1.24%)  2
Hyperthermia  1  2/164 (1.22%)  3 0/161 (0.00%)  0
Non-cardiac chest pain  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Pain  1  2/164 (1.22%)  2 0/161 (0.00%)  0
Pyrexia  1  2/164 (1.22%)  2 3/161 (1.86%)  3
Hepatobiliary disorders     
Bile duct obstruction  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Hepatic failure  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Immune system disorders     
Drug hypersensitivity  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Infections and infestations     
Cellulitis  1  1/164 (0.61%)  2 1/161 (0.62%)  1
Device related infection  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Erysipelas  1  1/164 (0.61%)  1 2/161 (1.24%)  2
Gastroenteritis  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Herpes zoster  1  2/164 (1.22%)  2 0/161 (0.00%)  0
Infected skin ulcer  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Klebsiella sepsis  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Lung infection  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Pneumonia  1  2/164 (1.22%)  2 3/161 (1.86%)  3
Scrotal abscess  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Sepsis  1  1/164 (0.61%)  1 1/161 (0.62%)  1
Septic shock  1  3/164 (1.83%)  3 0/161 (0.00%)  0
Streptococcal bacteraemia  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Urinary tract infection  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Urinary tract infection bacterial  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Wound infection  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Injury, poisoning and procedural complications     
Spinal compression fracture  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Spinal fracture  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Investigations     
Haemoglobin decreased  1  2/164 (1.22%)  2 1/161 (0.62%)  1
Metabolism and nutrition disorders     
Dehydration  1  2/164 (1.22%)  2 1/161 (0.62%)  1
Failure to thrive  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Hypercalcaemia  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Hyperglycaemia  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Hypokalaemia  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Musculoskeletal pain  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Pain in extremity  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant ascites  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Nervous system disorders     
Brain oedema  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Cauda equina syndrome  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Cerebral haematoma  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Cerebral haemorrhage  1  2/164 (1.22%)  2 0/161 (0.00%)  0
Grand mal convulsion  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Haemorrhage intracranial  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Haemorrhagic stroke  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Hepatic encephalopathy  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Speech disorder  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Spinal cord compression  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Syncope  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Psychiatric disorders     
Confusional state  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Panic attack  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Renal and urinary disorders     
Renal failure  1  1/164 (0.61%)  1 1/161 (0.62%)  1
Renal failure acute  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Reproductive system and breast disorders     
Balanitis  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Vaginal haemorrhage  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Dyspnoea  1  1/164 (0.61%)  1 2/161 (1.24%)  2
Haemoptysis  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Pleural effusion  1  2/164 (1.22%)  2 0/161 (0.00%)  0
Pneumothorax  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Pulmonary embolism  1  1/164 (0.61%)  1 4/161 (2.48%)  4
Pulmonary oedema  1  2/164 (1.22%)  2 0/161 (0.00%)  0
Respiratory failure  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Skin and subcutaneous tissue disorders     
Rash  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Vascular disorders     
Circulatory collapse  1  1/164 (0.61%)  1 0/161 (0.00%)  0
Deep vein thrombosis  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Hypotension  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Lymphoedema  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Pelvic venous thrombosis  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Peripheral ischaemia  1  0/164 (0.00%)  0 1/161 (0.62%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tasisulam-sodium Paclitaxel
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   149/164 (90.85%)      146/161 (90.68%)    
Blood and lymphatic system disorders     
Anaemia  1  15/164 (9.15%)  17 19/161 (11.80%)  21
Neutropenia  1  13/164 (7.93%)  17 19/161 (11.80%)  27
Thrombocytopenia  1  21/164 (12.80%)  28 2/161 (1.24%)  2
Gastrointestinal disorders     
Abdominal pain  1  12/164 (7.32%)  13 14/161 (8.70%)  16
Abdominal pain upper  1  10/164 (6.10%)  10 4/161 (2.48%)  4
Constipation  1  14/164 (8.54%)  16 23/161 (14.29%)  24
Diarrhoea  1  31/164 (18.90%)  39 29/161 (18.01%)  35
Dyspepsia  1  6/164 (3.66%)  6 9/161 (5.59%)  10
Nausea  1  29/164 (17.68%)  33 36/161 (22.36%)  37
Vomiting  1  16/164 (9.76%)  17 21/161 (13.04%)  21
General disorders     
Asthenia  1  10/164 (6.10%)  10 19/161 (11.80%)  21
Fatigue  1  50/164 (30.49%)  52 47/161 (29.19%)  50
Oedema peripheral  1  12/164 (7.32%)  14 15/161 (9.32%)  15
Pyrexia  1  17/164 (10.37%)  18 14/161 (8.70%)  15
Metabolism and nutrition disorders     
Decreased appetite  1  22/164 (13.41%)  22 20/161 (12.42%)  22
Musculoskeletal and connective tissue disorders     
Arthralgia  1  9/164 (5.49%)  11 6/161 (3.73%)  6
Back pain  1  7/164 (4.27%)  8 9/161 (5.59%)  9
Pain in extremity  1  5/164 (3.05%)  5 13/161 (8.07%)  14
Nervous system disorders     
Dizziness  1  5/164 (3.05%)  5 10/161 (6.21%)  11
Dysgeusia  1  10/164 (6.10%)  10 5/161 (3.11%)  5
Headache  1  22/164 (13.41%)  29 12/161 (7.45%)  13
Neuropathy peripheral  1  0/164 (0.00%)  0 9/161 (5.59%)  13
Peripheral sensory neuropathy  1  5/164 (3.05%)  6 11/161 (6.83%)  12
Psychiatric disorders     
Insomnia  1  5/164 (3.05%)  5 10/161 (6.21%)  10
Respiratory, thoracic and mediastinal disorders     
Cough  1  16/164 (9.76%)  16 21/161 (13.04%)  23
Dyspnoea  1  14/164 (8.54%)  17 19/161 (11.80%)  20
Epistaxis  1  5/164 (3.05%)  6 10/161 (6.21%)  10
Skin and subcutaneous tissue disorders     
Alopecia  1  15/164 (9.15%)  15 51/161 (31.68%)  52
Pruritus  1  11/164 (6.71%)  13 9/161 (5.59%)  11
Rash  1  23/164 (14.02%)  29 23/161 (14.29%)  25
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
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.
Results Point of Contact
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01006252     History of Changes
Other Study ID Numbers: 13101
H8K-MC-JZAO ( Other Identifier: Eli Lilly and Company )
First Submitted: October 30, 2009
First Posted: November 2, 2009
Results First Submitted: March 17, 2018
Results First Posted: July 17, 2018
Last Update Posted: July 17, 2018