Melanoma, Skin Neoplasms
Conditions
Keywords
melanoma, antiangiogenesis
Brief summary
This is a Phase 2 study being conducted at multiple centers in the United States and France. Patients having melanoma that has spread to other parts of the body (i.e., metastatic) are eligible to participate. Patients must have disease that has been treated with no more than 1 prior treatment for metastatic disease (prior adjuvant treatment for localized disease does not count as prior treatment for metastatic disease). The purpose of the study is to test whether the angiogenesis inhibitor AG-013736 is an effective treatment for metastatic melanoma as shown by the number of patients in the study who experience significant and durable tumor shrinkage.
Interventions
DRUGAxitinib [AG-013736]
VEGFR \[vascular endothelial growth factor Receptor\] and PDGFR \[Platelet-Derived Growth Factor Receptor\] inhibitor: Single agent AG-013736 starting dose 5 mg BID +/- 20% according to toxicity. Treatment until progression or unacceptable toxicity occurs.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically documented melanoma with metastases * No more than 1 prior systemic therapy for metastatic disease (prior adjuvant therapy with interferon does not count as prior therapy for metastatic disease)
Exclusion criteria
* History of hemoptysis (coughing up of blood) * Brain metastases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (OR) | Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 147 weeks | Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Baseline until the date of first documented progression or death due to any cause, assessed every 8 weeks up to 147 weeks | Time in days from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as first event date minus the date of first dose of study medication plus 1. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was Death). |
| Duration of Response (DR) | Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 147 weeks | Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response. |
| Overall Survival (OS) | Baseline to death due to any cause or at least 1 year after the initial dose for the last treated participant | Time in days from the start of study treatment to date of death due to any cause. OS was calculated as the death date minus the date of first dose of study medication plus 1. Death was determined from AE data (where outcome was death) or from follow-up contact data (where the participant current status was death). For participants who were alive, overall survival was censored at the last contact. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Population Pharmacokinetics for Axitinib (AG-013736) Plasma Concentrations | Day 1 (pre-dose), Day 29, Day 57 and then every 8 weeks up to 147 weeks | Population pharmacokinetic analysis involved mixed effects modeling using nonlinear mixed effects modeling (NONMEM) software. The intent of this analysis was to establish a basic population pharmacokinetic model for axitinib (AG-013736) and to determine inter-individual and residual variability in population (oral) clearance, and volume of distribution of drug. Relationship of demographic variables (gender, age, body weight, height and ethnicity), concomitant medications and measures of altered hepatic and renal function were examined by fitting measured axitinib (AG-013736) concentrations. |
| Plasma Concentrations of Soluble Proteins | Day 1 (pre-dose) and then every 8 weeks up to 147 weeks | Plasma concentrations of soluble proteins (vascular endothelial growth factor \[VEGF\], placental growth factor \[PlGF\] and soluble vascular endothelial growth factor receptor-2 \[sVEGFR2\]) may be associated with tumor angiogenesis or tumor physiology and may correlate with efficacy or biological activity. It is presented as ratio to baseline, which is obtained by dividing the plasma soluble protein concentration at each time point by its concentration at baseline. |
Countries
France, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Axitinib Axitinib (AG-013736) tablet administered orally at a dose of 5 mg BID in cycles of 4 weeks. Treatment was administered continuously until progression or unacceptable toxicity occurred. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Death | 5 |
| Overall Study | Lack of Efficacy | 23 |
| Overall Study | Withdrawal due to Disease Progression | 1 |
Baseline characteristics
| Characteristic | Axitinib |
|---|---|
| Age Continuous | 62.40 Years STANDARD_DEVIATION 15.56 |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 32 |
| serious Total, serious adverse events | 18 / 32 |
Outcome results
Primary
Percentage of Participants With Objective Response (OR)
Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time frame: Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 147 weeks
Population: Study population included all participants who received at least 1 dose of study medication and had at least one baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Axitinib | Percentage of Participants With Objective Response (OR) | 18.8 Percentage of participants |
Secondary
Duration of Response (DR)
Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Time frame: Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 147 weeks
Population: Subgroup of participants from the study population with a confirmed objective tumor response (CR or PR).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axitinib | Duration of Response (DR) | 179.0 Days |
Secondary
Overall Survival (OS)
Time in days from the start of study treatment to date of death due to any cause. OS was calculated as the death date minus the date of first dose of study medication plus 1. Death was determined from AE data (where outcome was death) or from follow-up contact data (where the participant current status was death). For participants who were alive, overall survival was censored at the last contact.
Time frame: Baseline to death due to any cause or at least 1 year after the initial dose for the last treated participant
Population: Study population included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axitinib | Overall Survival (OS) | 200.5 Days |
Secondary
Progression-free Survival (PFS)
Time in days from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as first event date minus the date of first dose of study medication plus 1. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was Death).
Time frame: Baseline until the date of first documented progression or death due to any cause, assessed every 8 weeks up to 147 weeks
Population: Study population included all participants who received at least 1 dose of study medication and had at least one baseline efficacy assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Axitinib | Progression-free Survival (PFS) | 117.5 Days |
Other Pre-specified
Plasma Concentrations of Soluble Proteins
Plasma concentrations of soluble proteins (vascular endothelial growth factor \[VEGF\], placental growth factor \[PlGF\] and soluble vascular endothelial growth factor receptor-2 \[sVEGFR2\]) may be associated with tumor angiogenesis or tumor physiology and may correlate with efficacy or biological activity. It is presented as ratio to baseline, which is obtained by dividing the plasma soluble protein concentration at each time point by its concentration at baseline.
Time frame: Day 1 (pre-dose) and then every 8 weeks up to 147 weeks
Population: Ratio to baseline values for plasma soluble proteins were not summarized as descriptive statistics since the data was not available for the single study and data for all the axitinib Phase 2 studies would be pooled together in a separate report.
Other Pre-specified
Population Pharmacokinetics for Axitinib (AG-013736) Plasma Concentrations
Population pharmacokinetic analysis involved mixed effects modeling using nonlinear mixed effects modeling (NONMEM) software. The intent of this analysis was to establish a basic population pharmacokinetic model for axitinib (AG-013736) and to determine inter-individual and residual variability in population (oral) clearance, and volume of distribution of drug. Relationship of demographic variables (gender, age, body weight, height and ethnicity), concomitant medications and measures of altered hepatic and renal function were examined by fitting measured axitinib (AG-013736) concentrations.
Time frame: Day 1 (pre-dose), Day 29, Day 57 and then every 8 weeks up to 147 weeks
Population: Population pharmacokinetic values were not summarized as descriptive statistics since the data was not available for the single study and data for all the axitinib (AG-013736) Phase 2 studies would be pooled together in a separate report.