Carcinoma, Renal Cell
Conditions
Brief summary
The purpose of this study is to test whether sunitinib (SU011248) has activity and is safe in patients with renal cell carcinoma (RCC) who have failed prior therapy with bevacizumab (Avastin) -based treatment.
Interventions
DRUGSunitinib
50 mg orally daily for 4 weeks followed by 2 weeks off treatment for approximately 1 year or until disease progression/unacceptable toxicity; after completion of 1 year, pts with clinical benefit can continue the study treatment in a separate continuation protocol
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 proven renal cell carcinoma of clear cell histology with metastases * Evidence of measurable disease * Radiographic evidence of disease progression during or within 3 months of completion of bevacizumab-based treatment * Prior radical or partial nephrectomy
Exclusion criteria
* Prior treatment with any other anti-angiogenic therapy other than bevacizumab * Prior systemic treatment for RCC \> 2 regimens * History of or known brain metastases * Serious acute or chronic illness or recent history of significant cardiac abnormality
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Overall Confirmed Objective Disease Response According to the Response Evaluation Criteria in Solid Tumors (RECIST) | 4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up | Objective disease response = subjects with confirmed complete response (CR) or partial response (PR) according to RECIST. A CR was defined as the disappearance of all target lesions. A PR was defined as a ≥ 30% 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 |
|---|---|---|
| Duration of Response (DR) | 4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up | DR was defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death due to to any cause that occurred within 28 days after the last dose of study medication, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR was only calculated for the subgroup of subjects with a confirmed objective response. DR was calculated as \[the end date for DR minus first CR or PR that was subsequently confirmed +1\]/7. Kaplan-Meier method was used. |
| Overall Survival (OS) | 4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up | OS was defined as the time from start of study treatment to date of death due to any cause. OS (in weeks) was calculated as \[date of death minus first dose date +1\]/7. For a subject not expiring, the OS time was censored on the last date of known contact that they were known to be alive. Subjects lacking data beyond the day of the first dose had their OS times censored at 1 day. Kaplan-Meier method was used. |
| Progression Free Survival (PFS) | 4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up | PFS was defined as the time from start of study medication to first documentation of objective tumor progression or to death due to any cause that occurred on treatment including within 28 days after the last dose of study medication, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date minus first dose date +1)/7. Kaplan-Meier method was used. |
| Trough Plasma Concentrations (Cmin) of Sunitinib | Day 28 of Cycle 1 to Cycle 4 | — |
| Trough Plasma Concentrations (Cmin) of SU012662 | Day 28 of Cycle 1 to Cycle 4 | — |
| Time to Tumor Progression (TTP) | 4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up | TTP was defined as the time from the date of first dose of study medication to the date of the first documentation of tumor progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date minus first dose date +1)/7. Kaplan-Meier method was used. |
| Plasma Concentration of Vascular Endothelial Growth Factor-A (VEGF-A) | Cycle 1 (Days 1, 14, and 28), Cycle 2 (Day 1) | Plasma concentrations of VEGF-A that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded. |
| Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3) | Cycle 1 (Days 1, 14, and 28), Cycle 2 (Day 1) | Plasma concentrations of sVEGFR-3 that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded. |
| Plasma Concentration of Placental Growth Factor (PlGF) | Cycle 1 (Days 1, 14, and 28) | Plasma concentrations of PlGF that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded. |
| Plasma Concentration of VEGF-C | Cycle 1 (Days 1, 14, and 28) | Plasma concentrations of VEGF-C that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded. |
| Plasma Concentration of Soluble VEGF Receptor-2(sVEGFR-2) | 1 year | Plasma concentrations of sVEGFR-2 that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were to have been analyzed by ELISA analysis; however, no data were collected. |
| Trough Plasma Concentrations (Cmin) of Total Drug (Sunitinib + SU012662) | Day 28 of Cycle 1 to Cycle 4 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib 50 milligram/day for 4 consecutive weeks followed by a 2-week off-treatment period (6-week treatment cycle). | 61 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Lack of Efficacy | 33 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Sunitinib |
|---|---|
| Age, Customized < 65 years | 43 participants |
| Age, Customized > = 65 years | 18 participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 60 / 61 |
| serious Total, serious adverse events | 30 / 61 |
Outcome results
Primary
Number of Subjects With Overall Confirmed Objective Disease Response According to the Response Evaluation Criteria in Solid Tumors (RECIST)
Objective disease response = subjects with confirmed complete response (CR) or partial response (PR) according to RECIST. A CR was defined as the disappearance of all target lesions. A PR was defined as a ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time frame: 4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up
Population: Intent-to-treat (ITT)=all subjects enrolled in the study that received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib | Number of Subjects With Overall Confirmed Objective Disease Response According to the Response Evaluation Criteria in Solid Tumors (RECIST) | 14 participants |
95% CI: [13.2, 35.5]
Secondary
Duration of Response (DR)
DR was defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death due to to any cause that occurred within 28 days after the last dose of study medication, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR was only calculated for the subgroup of subjects with a confirmed objective response. DR was calculated as \[the end date for DR minus first CR or PR that was subsequently confirmed +1\]/7. Kaplan-Meier method was used.
Time frame: 4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up
Population: ITT subjects (i.e, all subjects enrolled in the study that received at least 1 dose of study medication) who had a confirmed CR or PR. 14 subjects who had a response were analyzed for DR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Duration of Response (DR) | 36.1 weeks |
Secondary
Overall Survival (OS)
OS was defined as the time from start of study treatment to date of death due to any cause. OS (in weeks) was calculated as \[date of death minus first dose date +1\]/7. For a subject not expiring, the OS time was censored on the last date of known contact that they were known to be alive. Subjects lacking data beyond the day of the first dose had their OS times censored at 1 day. Kaplan-Meier method was used.
Time frame: 4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Overall Survival (OS) | 47.1 weeks |
Secondary
Plasma Concentration of Placental Growth Factor (PlGF)
Plasma concentrations of PlGF that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Time frame: Cycle 1 (Days 1, 14, and 28)
Population: ITT
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Sunitinib | Plasma Concentration of Placental Growth Factor (PlGF) | Cycle 1, Day 1 (Baseline) (n=37) | 55.0 pg/mL |
| Sunitinib | Plasma Concentration of Placental Growth Factor (PlGF) | Cycle 1, Day 14 (n=58) | 146.1 pg/mL |
| Sunitinib | Plasma Concentration of Placental Growth Factor (PlGF) | Cycle 1, Day 28 (n=53) | 137.9 pg/mL |
Secondary
Plasma Concentration of Soluble VEGF Receptor-2(sVEGFR-2)
Plasma concentrations of sVEGFR-2 that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were to have been analyzed by ELISA analysis; however, no data were collected.
Time frame: 1 year
Secondary
Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3)
Plasma concentrations of sVEGFR-3 that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Time frame: Cycle 1 (Days 1, 14, and 28), Cycle 2 (Day 1)
Population: ITT
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Sunitinib | Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3) | Cycle 1, Day 1 (Baseline) (n=54) | 54170.4 pg/mL |
| Sunitinib | Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3) | Cycle 1, Day 14 (n=32) | 37747.0 pg/mL |
| Sunitinib | Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3) | Cycle 1, Day 28 (n=22) | 46891.0 pg/mL |
| Sunitinib | Plasma Concentration of Soluble VEGF Receptor-3 (sVEGFR-3) | Cycle 2, Day 1 (n=46) | 51280.0 pg/mL |
Secondary
Plasma Concentration of Vascular Endothelial Growth Factor-A (VEGF-A)
Plasma concentrations of VEGF-A that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Time frame: Cycle 1 (Days 1, 14, and 28), Cycle 2 (Day 1)
Population: ITT
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Sunitinib | Plasma Concentration of Vascular Endothelial Growth Factor-A (VEGF-A) | Cycle 1, Day 1 (Baseline) (n=59) | 567.4 pg/mL |
| Sunitinib | Plasma Concentration of Vascular Endothelial Growth Factor-A (VEGF-A) | Cycle 1, Day 14 (n=57) | 1320.6 pg/mL |
| Sunitinib | Plasma Concentration of Vascular Endothelial Growth Factor-A (VEGF-A) | Cycle 1, Day 28 (n=55) | 1212.3 pg/mL |
| Sunitinib | Plasma Concentration of Vascular Endothelial Growth Factor-A (VEGF-A) | Cycle 2, Day 1 (n=54) | 316.2 pg/mL |
Secondary
Plasma Concentration of VEGF-C
Plasma concentrations of VEGF-C that may be associated with tumor proliferation or angiogenesis collected from a subset of subjects were analyzed by ELISA analysis. Samples below the limit of quantitation and samples with insufficient volume available were excluded.
Time frame: Cycle 1 (Days 1, 14, and 28)
Population: ITT
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Sunitinib | Plasma Concentration of VEGF-C | Cycle 1, Day 1 (Baseline) (n=57) | 833.0 pg/mL |
| Sunitinib | Plasma Concentration of VEGF-C | Cycle 1, Day 14 (n=57) | 688.0 pg/mL |
| Sunitinib | Plasma Concentration of VEGF-C | Cycle 1, Day 28 (n=54) | 566.5 pg/mL |
Secondary
Progression Free Survival (PFS)
PFS was defined as the time from start of study medication to first documentation of objective tumor progression or to death due to any cause that occurred on treatment including within 28 days after the last dose of study medication, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date minus first dose date +1)/7. Kaplan-Meier method was used.
Time frame: 4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up
Population: ITT. 20 subjects were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Progression Free Survival (PFS) | 30.4 weeks |
Secondary
Time to Tumor Progression (TTP)
TTP was defined as the time from the date of first dose of study medication to the date of the first documentation of tumor progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date minus first dose date +1)/7. Kaplan-Meier method was used.
Time frame: 4 week treatment cycles up to 1 year in absence of withdrawal criteria requiring discontinuation including 28 day post study follow up
Population: ITT. 20 subjects were censored.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Time to Tumor Progression (TTP) | 30.4 weeks |
Secondary
Trough Plasma Concentrations (Cmin) of SU012662
Time frame: Day 28 of Cycle 1 to Cycle 4
Population: ITT
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sunitinib | Trough Plasma Concentrations (Cmin) of SU012662 | Cycle 1, Day 28 (n=20) | 30.50 ng/mL |
| Sunitinib | Trough Plasma Concentrations (Cmin) of SU012662 | Cycle 2, Day 28 (n=23) | 21.40 ng/mL |
| Sunitinib | Trough Plasma Concentrations (Cmin) of SU012662 | Cycle 3, Day 28 (n=10) | 22.10 ng/mL |
| Sunitinib | Trough Plasma Concentrations (Cmin) of SU012662 | Cycle 4, Day 28 (n=16) | 23.75 ng/mL |
Secondary
Trough Plasma Concentrations (Cmin) of Sunitinib
Time frame: Day 28 of Cycle 1 to Cycle 4
Population: ITT
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sunitinib | Trough Plasma Concentrations (Cmin) of Sunitinib | Cycle 1, Day 28 (n=20) | 52.05 ng/mL |
| Sunitinib | Trough Plasma Concentrations (Cmin) of Sunitinib | Cycle 2, Day 28 (n=23) | 43.50 ng/mL |
| Sunitinib | Trough Plasma Concentrations (Cmin) of Sunitinib | Cycle 3, Day 28 (n=10) | 46.10 ng/mL |
| Sunitinib | Trough Plasma Concentrations (Cmin) of Sunitinib | Cycle 4, Day 28 (n=16) | 44.90 ng/mL |
Secondary
Trough Plasma Concentrations (Cmin) of Total Drug (Sunitinib + SU012662)
Time frame: Day 28 of Cycle 1 to Cycle 4
Population: ITT
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sunitinib | Trough Plasma Concentrations (Cmin) of Total Drug (Sunitinib + SU012662) | Cycle 1, Day 28 (n=20) | 85.40 ng/mL |
| Sunitinib | Trough Plasma Concentrations (Cmin) of Total Drug (Sunitinib + SU012662) | Cycle 2, Day 28 (n=23) | 66.60 ng/mL |
| Sunitinib | Trough Plasma Concentrations (Cmin) of Total Drug (Sunitinib + SU012662) | Cycle 3, Day 28 (n=10) | 68.40 ng/mL |
| Sunitinib | Trough Plasma Concentrations (Cmin) of Total Drug (Sunitinib + SU012662) | Cycle 4, Day 28 (n=16) | 68.15 ng/mL |