Melanoma
Conditions
Keywords
metastatic, second-line
Brief summary
The primary purpose of this study was to see how tasisulam-sodium affected metastatic melanoma when compared against paclitaxel as measured by overall survival.
Interventions
DRUGTasisulam-sodium
Administered intravenously on Day 1 of a 28-day cycle, until disease progression.
DRUGPaclitaxel
80 mg/m\^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle, until disease progression
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a histologic and/or cytologic diagnosis of metastatic melanoma (Stage IV). * Have the presence of evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.0). * Have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) Scale. * Have progressed after 1 previous systemic treatment containing dacarbazine or temozolomide for metastatic melanoma. * Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, or other investigational therapy for at least 30 days (6 weeks for mitomycin-C or nitrosoureas) before study enrollment and recovered from the acute effects of therapy (except alopecia). * Have a serum albumin level greater than or equal to 3.0 grams per deciliter (g/dL) or greater than or equal to 30 grams per liter (g/L).
Exclusion criteria
* Have received greater than or equal to 2 previous chemotherapy-containing systemic treatment regimens for metastatic melanoma. An immunotherapy or antibody-based regimen (including biologic agents and vaccination-based treatments), or treatment with a targeted agent (for example, BRAF or c-Kit inhibitor is not counted as a prior treatment regimen for determining study eligibility, unless either was combined with a cytotoxic drug). * Have active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of study entry. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before study entry to rule out occult brain metastasis. Participants with a history of a solitary CNS metastasis previously treated with curative intent (for example, stereotactic radiation or surgery) and not requiring steroids are eligible. * Are receiving warfarin. * Have primary ocular or mucosal melanoma. * Any previous treatment with paclitaxel or a paclitaxel-containing regimen for metastatic melanoma. * Have serious concomitant disorders, including active bacterial, fungal, or viral infection, incompatible with the study (at the discretion of the investigator). * Have previously completed or withdrawn from this study or any other study investigating tasisulam-sodium. * Have a known hypersensitivity to paclitaxel or Cremophor EL (polyoxyethylated castor oil). * Are pregnant or lactating. * Have received a recent (within 30 days before enrollment) or are receiving concurrent yellow fever vaccination. * Have known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb). * Are unable to withhold dosing of non-steroidal anti-inflammatory drugs (NSAIDs) or proton-pump inhibitors (PPIs) for at least 72 hours before and after treatment with tasisulam-sodium.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Randomization to date of death from any cause (assessed at every cycle and every 60 days following treatment discontinuation) up to 14.32 months | OS is duration from enrollment to death; OS censored for participants who were alive at last contact. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Randomized Participants Having a Confirmed Best Response of Partial Response (PR) or Complete Response (CR) | 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 | 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. |
| Duration of Response (DoR) for Participants Having an Objective Response of Partial Response (PR) or Complete Response (CR) | 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 | 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. |
| 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) | 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 | 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 to Deterioration in the Functional Assessment of Cancer Therapy-Melanoma Trial Outcome Index (FACT-M TOI) Score | 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 | 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. |
| Change From Baseline at Cycle 2 in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) up to 30 Days Following Treatment Discontinuation | Baseline at Cycle 2, up to 30 days following treatment discontinuation | 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. |
| Change From Baseline at Cycle 3 in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) up to 30 Days Following Treatment Discontinuation | Baseline at Cycle 3, up to 30 days following treatment discontinuation | 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. |
| Progression Free Survival (PFS) | 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 | 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. |
| Change From Baseline at Cycle 2 in EuroQol-5 Dimensions (EQ-5D) up to 30 Days Following Treatment Discontinuation | Baseline at Cycle 2, up to 30 days following treatment discontinuation | 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. |
| Change From Baseline at Cycle 3 in EuroQol-5 Dimensions (EQ-5D) up to 30 Days Following Treatment Discontinuation | Baseline at Cycle 3, up to 30 days following treatment discontinuation | 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. |
| Change From Baseline at Cycle 4 Baseline in EuroQol-5 Dimensions (EQ-5D) up to 30 Days Following Treatment Discontinuation | Baseline at Cycle 4, up to 30 days after treatment discontinuation | 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. |
| Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) During Cycle 1 | After drug infusion in Cycle 1 (5 samples drawn over the 28-day cycle) | — |
| Pharmacokinetics: Maximum Plasma Concentration (Cmax) During Cycle 2 | After drug infusion in Cycle 2 (2 samples drawn over the 28-day cycle) | — |
| Change From Baseline at Cycle 4 in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) up to 30 Days Following Treatment Discontinuation | Baseline at Cycle 4, up to 30 days following treatment discontinuation | 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. |
Countries
Australia, Austria, Belgium, Canada, Finland, France, Germany, Israel, Italy, Netherlands, Norway, Poland, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tasisulam-sodium 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. | 168 |
| Paclitaxel Paclitaxel 80 mg/m\^2 administered intravenously on Days 1, 8, and 15 of a 28-day cycle, until disease progression | 168 |
| Total | 336 |
Baseline characteristics
| Characteristic | Total | Tasisulam-sodium | Paclitaxel |
|---|---|---|---|
| Age, Continuous | 58.87 years STANDARD_DEVIATION 13.31 | 58.30 years STANDARD_DEVIATION 13.2 | 59.44 years STANDARD_DEVIATION 13.43 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 159 Participants | 84 Participants | 75 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 172 Participants | 83 Participants | 89 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 320 Participants | 158 Participants | 162 Participants |
| Region of Enrollment Australia | 6 Participants | 1 Participants | 5 Participants |
| Region of Enrollment Austria | 8 Participants | 5 Participants | 3 Participants |
| Region of Enrollment Belgium | 13 Participants | 7 Participants | 6 Participants |
| Region of Enrollment Canada | 12 Participants | 4 Participants | 8 Participants |
| Region of Enrollment Finland | 3 Participants | 1 Participants | 2 Participants |
| Region of Enrollment France | 58 Participants | 32 Participants | 26 Participants |
| Region of Enrollment Germany | 60 Participants | 32 Participants | 28 Participants |
| Region of Enrollment Israel | 6 Participants | 3 Participants | 3 Participants |
| Region of Enrollment Italy | 19 Participants | 8 Participants | 11 Participants |
| Region of Enrollment Norway | 10 Participants | 5 Participants | 5 Participants |
| Region of Enrollment Poland | 13 Participants | 7 Participants | 6 Participants |
| Region of Enrollment South Korea | 13 Participants | 9 Participants | 4 Participants |
| Region of Enrollment Spain | 10 Participants | 3 Participants | 7 Participants |
| Region of Enrollment Sweden | 6 Participants | 3 Participants | 3 Participants |
| Region of Enrollment United Kingdom | 9 Participants | 8 Participants | 1 Participants |
| Region of Enrollment United States | 90 Participants | 40 Participants | 50 Participants |
| Sex: Female, Male Female | 128 Participants | 65 Participants | 63 Participants |
| Sex: Female, Male Male | 208 Participants | 103 Participants | 105 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 149 / 164 | 146 / 161 |
| serious Total, serious adverse events | 53 / 164 | 44 / 161 |
Outcome results
Primary
Overall Survival (OS)
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
Population: The intent-to-treat (ITT) analysis population included all participants randomized to treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tasisulam-sodium | Overall Survival (OS) | 6.77 months |
| Paclitaxel | Overall Survival (OS) | 9.36 months |
p-value: 0.121Stratified log rank
Secondary
Change From Baseline at Cycle 2 in EuroQol-5 Dimensions (EQ-5D) up to 30 Days Following Treatment Discontinuation
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
Population: The analysis population included all randomized participants who had baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tasisulam-sodium | Change From Baseline at Cycle 2 in EuroQol-5 Dimensions (EQ-5D) up to 30 Days Following Treatment Discontinuation | 0.01 units on a scale | Standard Error 0.03 |
| Paclitaxel | Change From Baseline at Cycle 2 in EuroQol-5 Dimensions (EQ-5D) up to 30 Days Following Treatment Discontinuation | -0.00 units on a scale | Standard Error 0.03 |
p-value: 0.547Mixed Model Repeated Measures (MMRM)
p-value: 0.414Mixed Model Repeated Measures (MMRM)
Secondary
Change From Baseline at Cycle 2 in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) up to 30 Days Following Treatment Discontinuation
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
Population: The analysis population included all randomized participants who had baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tasisulam-sodium | Change From Baseline at Cycle 2 in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) up to 30 Days Following Treatment Discontinuation | -0.81 units on a scale | Standard Error 2.38 |
| Paclitaxel | Change From Baseline at Cycle 2 in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) up to 30 Days Following Treatment Discontinuation | -1.07 units on a scale | Standard Error 2.4 |
p-value: 0.902Mixed Model Repeated Measures (MMRM)
p-value: 0.97Mixed Model Repeated Measures (MMRM)
Secondary
Change From Baseline at Cycle 3 in EuroQol-5 Dimensions (EQ-5D) up to 30 Days Following Treatment Discontinuation
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
Population: The analysis population included all randomized participants who had baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tasisulam-sodium | Change From Baseline at Cycle 3 in EuroQol-5 Dimensions (EQ-5D) up to 30 Days Following Treatment Discontinuation | -0.01 units on a scale | Standard Error 0.03 |
| Paclitaxel | Change From Baseline at Cycle 3 in EuroQol-5 Dimensions (EQ-5D) up to 30 Days Following Treatment Discontinuation | -0.06 units on a scale | Standard Error 0.03 |
Secondary
Change From Baseline at Cycle 3 in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) up to 30 Days Following Treatment Discontinuation
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
Population: The analysis population included all randomized participants who had baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tasisulam-sodium | Change From Baseline at Cycle 3 in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) up to 30 Days Following Treatment Discontinuation | -4.06 units on a scale | Standard Error 2.47 |
| Paclitaxel | Change From Baseline at Cycle 3 in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) up to 30 Days Following Treatment Discontinuation | -4.69 units on a scale | Standard Error 2.51 |
Secondary
Change From Baseline at Cycle 4 Baseline in EuroQol-5 Dimensions (EQ-5D) up to 30 Days Following Treatment Discontinuation
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
Population: The analysis population included all randomized participants who had baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tasisulam-sodium | Change From Baseline at Cycle 4 Baseline in EuroQol-5 Dimensions (EQ-5D) up to 30 Days Following Treatment Discontinuation | -0.05 units on a scale | Standard Error 0.04 |
| Paclitaxel | Change From Baseline at Cycle 4 Baseline in EuroQol-5 Dimensions (EQ-5D) up to 30 Days Following Treatment Discontinuation | -0.05 units on a scale | Standard Error 0.04 |
p-value: 0.547Mixed Model Repeated Measures (MMRM)
p-value: 0.414Mixed Model Repeated Measures (MMRM)
Secondary
Change From Baseline at Cycle 4 in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) up to 30 Days Following Treatment Discontinuation
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
Population: The analysis population included all randomized participants who had baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tasisulam-sodium | Change From Baseline at Cycle 4 in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) up to 30 Days Following Treatment Discontinuation | -2.86 units on a scale | Standard Error 2.66 |
| Paclitaxel | Change From Baseline at Cycle 4 in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) up to 30 Days Following Treatment Discontinuation | -2.98 units on a scale | Standard Error 2.69 |
p-value: 0.902Mixed Model Repeated Measures (MMRM)
p-value: 0.97Mixed Model Repeated Measures (MMRM)
Secondary
Duration of Response (DoR) for Participants Having an Objective Response of Partial Response (PR) or Complete Response (CR)
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
Population: Zero participants analyzed. Duration of Response for CR and PR data was not collected for analysis per study report.
Secondary
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)
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
Population: The intent-to-treat (ITT) analysis population included all participants randomized to treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tasisulam-sodium | 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) | 30.4 percentage of participants |
| Paclitaxel | 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) | 33.9 percentage of participants |
p-value: 0.483Unadjusted normal distribution
Secondary
Percentage of Randomized Participants Having a Confirmed Best Response of Partial Response (PR) or Complete Response (CR)
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
Population: The intent-to-treat (ITT) analysis population included all participants randomized to treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tasisulam-sodium | Percentage of Randomized Participants Having a Confirmed Best Response of Partial Response (PR) or Complete Response (CR) | CR | 0 percentage of participants |
| Tasisulam-sodium | Percentage of Randomized Participants Having a Confirmed Best Response of Partial Response (PR) or Complete Response (CR) | PR | 3.0 percentage of participants |
| Paclitaxel | Percentage of Randomized Participants Having a Confirmed Best Response of Partial Response (PR) or Complete Response (CR) | CR | 0 percentage of participants |
| Paclitaxel | Percentage of Randomized Participants Having a Confirmed Best Response of Partial Response (PR) or Complete Response (CR) | PR | 4.8 percentage of participants |
p-value: 0.396Unadjusted normal distribution
Secondary
Pharmacokinetics: Maximum Plasma Concentration (Cmax) During Cycle 2
Time frame: After drug infusion in Cycle 2 (2 samples drawn over the 28-day cycle)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tasisulam-sodium | Pharmacokinetics: Maximum Plasma Concentration (Cmax) During Cycle 2 | 361 µg/mL | Geometric Coefficient of Variation 16.8 |
Secondary
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) During Cycle 1
Time frame: After drug infusion in Cycle 1 (5 samples drawn over the 28-day cycle)
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Tasisulam-sodium | Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) During Cycle 1 | 375 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 14.8 |
Secondary
Progression Free Survival (PFS)
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
Population: The intent-to-treat (ITT) analysis population included all participants randomized to treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tasisulam-sodium | Progression Free Survival (PFS) | 1.94 months |
| Paclitaxel | Progression Free Survival (PFS) | 2.14 months |
p-value: 0.048Stratified log rank
Secondary
Time to Deterioration in the Functional Assessment of Cancer Therapy-Melanoma Trial Outcome Index (FACT-M TOI) Score
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
Population: The analysis population included all randomized participants who had baseline and at least 1 post-baseline measurement.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tasisulam-sodium | Time to Deterioration in the Functional Assessment of Cancer Therapy-Melanoma Trial Outcome Index (FACT-M TOI) Score | 2.96 months |
| Paclitaxel | Time to Deterioration in the Functional Assessment of Cancer Therapy-Melanoma Trial Outcome Index (FACT-M TOI) Score | 3.52 months |
p-value: 0.505Stratified log rank