Prostatic Neoplasms
Conditions
Keywords
First-line treatment of metastatic hormone-refractory prostate cancer SUTENT in combination with docetaxel and prednisone
Brief summary
This is a multi-center, open-label, Phase 1/2 study of SU011248 (sunitinib malate, SUTENT) in combination with docetaxel and prednisone for the first-line treatment of metastatic hormone-refractory prostate cancer (mHRPC).
Interventions
DRUGDocetaxel
Docetaxel Phase 1 - escalating doses (60 and 75 mg/m2), intravenous therapy (IV), administered every 3 weeks. Phase 2 - Phase 1 optimal combination dose (75 mg/m2, IV, every 3 weeks).
DRUGPrednisone
Prednisone Phase1/2 - 5 mg twice a day (BID), oral.
DRUGSU011248
SU011248 Phase 1 - escalating doses (12.5, 37.5, and 50 mg), oral, administered on a 2-weeks on, 1-week off daily regimen (Schedule 2/1). Phase 2 - Phase 1 optimal combination dose (37.5 mg/day, oral, Schedule 2/1).
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed adenocarcinoma of the prostate * Patients must have progressive hormone-refractory prostate cancer (HRPC): patients must have undergone primary hormone treatment (e.g. orchiectomy or gonadotropin releasing hormone analog with or without antiandrogens). For patients who received antiandrogen therapy, disease progression must have been determined after antiandrogen discontinuation * Progressive disease based on either non-measurable disease and an elevated PSA OR measurable disease * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Exclusion criteria
* Prior thalidomide, anti-vascular endothelial growth factor (VEGF) therapy, VEGF receptor inhibitor, platelet-derived growth factor (PDGF) receptor inhibitor or anti-angiogenic treatment of any kind including investigational therapy * Prior chemotherapy * Uncontrolled pain at baseline, impending complication from bone metastasis (fracture and/or compression) and/or presence of urinary obstruction (urinary retention, hydronephrosis) * History of cardiac dysfunction, QT interval corrected for heart rate (QTc) \>450 msec * Central Nervous System (CNS) involvement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Prostate Specific Antigen (PSA) Response | Baseline, Day 1 of each 21-day cycle | PSA response rate, which is defined as a greater than or equal to a 50% decrease in PSA from baseline, that is subsequently confirmed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of PSA Response (DPR) | Baseline to first documentation of PSA progression up to 28 days after date of last dose | Defined as time from first documentation of PSA response (≥50% decrease in PSA from baseline that is subsequently confirmed) to first documentation of PSA progression (defined for patients with a PSA response as a 50% increase over nadir \[lowest\] and increase in absolute-value PSA level by at least 5 ng/mL \[or back to baseline\] and for patients without a PSA response as a 25% increase over baseline \[or nadir / lowest\] and increase in absolute-value PSA level by at least 5 ng/mL, both confirmed by a second value). Calculated as (end date for DPR - first PSA response + 1)/7. |
| Percentage of Participants With Objective Response Rate (ORR) | Baseline to first documentation of PSA progression up to 28 days after date of last dose | Defined as confirmed complete response (CR: disappearance of all target lesions) or confirmed partial response (PR: ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD) according to response evaluation criteria in solid tumors (RECIST). Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. |
| Ratio to Baseline (Bsl) in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFC | Baseline (Cycle 1 Day 1 [C1.D1]), C1.D14, C2.D1, C2.D14, C3.D1, C3.D14 | Soluble protein biomarker Vascular Endothelial Growth Factor C (VEGFC) measured as picograms per milliliter (pg/mL). PSA responders are participants with a confirmed PSA response as per the Working Group criteria (\>50% decrease from baseline) and non-responders are those not meeting the definition of responder. Ratio=value of soluble protein biomarkers at each time point to the value at baseline (C1D14 : C1D1). |
| Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR2 | Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D1, C3.D14 | Soluble protein biomarker Vascular Endothelial Growth Factor receptor 2 (VEGFR2) measured as pg/mL. PSA responders are participants with a confirmed PSA response as per the Working Group criteria (\>50% decrease from baseline) and non-responders are those not meeting the definition of responder. Ratio=value of soluble protein biomarkers at each time point to the value at baseline (C1D14 : C1D1). |
| Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR3 | Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D1, C3.D14 | Soluble protein biomarker Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) measured as picograms per milliliter (pg/mL). PSA responders are participants with a confirmed PSA response as per the Working Group criteria (\>50% decrease from baseline) and non-responders are those not meeting the definition of responder. Ratio=value of soluble protein biomarkers at each time point to the value at baseline (C1D14 : C1D1). |
| Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFC | Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D14 | Soluble protein biomarker VEGFC measured as pg/mL. CBR defined as confirmed CR (disappearance of all target lesions) or confirmed PR (≥30% decrease in sum of longest dimensions \[LD\] of target lesions taking as reference the baseline sum LD) or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) ≥3 months versus PD (≥20% increase in sum LD of target lesions taking as reference the smallest sum LD recorded since treatment started, unequivocal progression of existing non-target lesions, or appearance of ≥1 new lesions) or SD \<3 months. |
| Time to PSA Progression | Baseline to first documentation of PSA progression up to 28 days after date of last dose | Defined as the time from start of study treatment to first documentation of PSA progression using the PSA Working Group criteria calculated as (first event date - first dose date + 1)/7. PSA progression is defined for patients with a PSA response, as a 50% increase over nadir (lowest) and increase in absolute-value PSA level by at least 5 nanograms per milliliter (ng/mL) \[or back to baseline\] and for patients without a PSA response as a 25% increase over baseline \[or nadir (lowest)\] and increase in absolute-value PSA level by at least 5 ng/mL, both confirmed by a second value. |
| Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR3 | Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D14 | Soluble protein biomarker VEGFR3 measured as pg/mL. CBR defined as confirmed CR (disappearance of all target lesions) or confirmed PR (≥30% decrease in sum of longest dimensions \[LD\] of target lesions taking as reference the baseline sum LD) or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) ≥3 months versus PD (≥20% increase in sum LD of target lesions taking as reference the smallest sum LD recorded since treatment started, unequivocal progression of existing non-target lesions, or appearance of ≥1 new lesions) or SD \<3 months. |
| Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Baseline (C1.D1), Day 1 of Cycles 2 through 16, and End of Treatment (EOT=following Cycle 16 or within 7 days of withdrawal from study) | The questionnaire assesses pain intensity (worst, least, average, and right now), level of relief in the last 24 hours, and the impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). The pain intensity index score was derived from Questions 2-5 with range from 0 to 10 (0: no pain; 1-4: mild pain; 5-6: moderate pain; 7-10: severe pain); higher scores indicate worse health status. |
| Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Baseline (C1.D1), Day 1 of Cycles 2 through 16, and End of Treatment (EOT=following Cycle 16 or within 7 days of withdrawal from study) | The questionnaire assesses pain intensity (worst, least, average, and right now), level of relief in the last 24 hours, and the impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). The pain interference index score (to measure how much pain had interfered with daily activities) was derived from Questions 7A-7G with a range from 0 (no interference) to 10 (completely interferes); higher scores indicate more interference. |
| Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Baseline (C1.D1), Day 1 of Cycles 2 through 16, and End of Treatment (EOT=following Cycle 16 or within 7 days of withdrawal from study) | Assesses health related quality of life and advanced prostate cancer specific symptoms. FACT-General (FACT-G) assesses 4 domains: physical, social and family, emotional, and functional well-being. The prostate cancer subscale assesses prostate cancer symptoms focusing on pain, urination problems, and sexual functions. Individual scores range from 0 (not at all) to 4 (very much). Scores for some of the individual questions are reverse-coded in order for higher scores to correspond to better health status. FACT-P overall score range is 0 to 156; higher scores indicate better health status. |
| Preliminary Assessment of PSA Modulation by SU011248 | Baseline to Day 28 | PSA modulation analyzed by the mean change in PSA response measured as ng/mL. |
| Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR2 | Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D14 | Soluble protein biomarker VEGFR2 measured as pg/mL. CBR defined as confirmed CR (disappearance of all target lesions) or confirmed PR (≥30% decrease in sum of longest dimensions \[LD\] of target lesions taking as reference the baseline sum LD) or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) ≥3 months versus PD (≥20% increase in sum LD of target lesions taking as reference the smallest sum LD recorded since treatment started, unequivocal progression of existing non-target lesions, or appearance of ≥1 new lesions) or SD \<3 months. |
Countries
United States
Participant flow
Pre-assignment details
Once the Optimal Combination Dose of SU011248, Docetaxel, and prednisone was determined in Phase 1, the study proceeded to Phase 2. There were 38 participants in Phase 1; those participants did not continue into Phase 2. Per FDAAA, only Phase 2 data are posted; timeframes are relative to Phase 2.
Participants by arm
| Arm | Count |
|---|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg SU011248 (Sunitinib Malate) 37.5 mg + Docetaxel 75 mg/m\^2 + Prednisone 5 mg given twice daily | 55 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 13 |
| Overall Study | Death | 2 |
| Overall Study | Lack of Efficacy | 17 |
| Overall Study | Other | 5 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 29 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Age Continuous | 65.8 years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 55 / 55 |
| serious Total, serious adverse events | 28 / 55 |
Outcome results
Primary
Percentage of Participants With Prostate Specific Antigen (PSA) Response
PSA response rate, which is defined as a greater than or equal to a 50% decrease in PSA from baseline, that is subsequently confirmed.
Time frame: Baseline, Day 1 of each 21-day cycle
Population: The intent-to-treat (ITT) population was defined as all patients enrolled in the study that receive at least 1 dose of study medication (SU011248 or docetaxel)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Percentage of Participants With Prostate Specific Antigen (PSA) Response | 56.4 percentage of participants |
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale)
Assesses health related quality of life and advanced prostate cancer specific symptoms. FACT-General (FACT-G) assesses 4 domains: physical, social and family, emotional, and functional well-being. The prostate cancer subscale assesses prostate cancer symptoms focusing on pain, urination problems, and sexual functions. Individual scores range from 0 (not at all) to 4 (very much). Scores for some of the individual questions are reverse-coded in order for higher scores to correspond to better health status. FACT-P overall score range is 0 to 156; higher scores indicate better health status.
Time frame: Baseline (C1.D1), Day 1 of Cycles 2 through 16, and End of Treatment (EOT=following Cycle 16 or within 7 days of withdrawal from study)
Population: PRO evaluable population; (n)=number of participants with evaluable data at observation.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Bsl mean C1.D1 (n=47) | 112.0 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Change from Bsl - C2.D1 (n=42) | 6.4 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Change from Bsl - C3.D1 (n=31) | 7.2 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Change from Bsl - C4.D1 (n=30) | 6.6 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Change from Bsl - C5.D1 (n=33) | 4.9 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Change from Bsl - C6.D1 (n=31) | 8.2 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Change from Bsl - C7.D1 (n=29) | 4.4 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Change from Bsl - C8.D1 (n=25) | 3.6 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Change from Bsl - C9.D1 (n=24) | 0.2 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Change from Bsl - C10.D1 (n=22) | 2.0 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Change from Bsl - C11.D1 (n=21) | 3.1 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Change from Bsl - C12.D1 (n=18) | 4.1 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Change from Bsl - C13.D1 (n=16) | 5.6 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Change from Bsl - C14.D1 (n=17) | 7.9 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Change from Bsl - C15.D1 (n=12) | 4.1 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Change from Bsl - C16.D1 (n=12) | 6.2 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) | Change from Bsl - EOT (n=36) | 0.6 scores on a scale |
Secondary
Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5)
The questionnaire assesses pain intensity (worst, least, average, and right now), level of relief in the last 24 hours, and the impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). The pain intensity index score was derived from Questions 2-5 with range from 0 to 10 (0: no pain; 1-4: mild pain; 5-6: moderate pain; 7-10: severe pain); higher scores indicate worse health status.
Time frame: Baseline (C1.D1), Day 1 of Cycles 2 through 16, and End of Treatment (EOT=following Cycle 16 or within 7 days of withdrawal from study)
Population: Patient reported outcomes (PRO) evaluable population defined as participants in the ITT population who received at least 1 dose of study medication (sunitinib or docetaxel) and had baseline data; (n)=number of participants with evaluable data at observation.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Bsl mean C1.D1 (n=48) | 1.9 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Change from Bsl - C2.D1 (n=42) | -1.0 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Change from Bsl - C3.D1 (n=35) | -1.1 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Change from Bsl - C4.D1 (n=30) | -0.8 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Change from Bsl - C5.D1 (n=32) | -0.8 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Change from Bsl - C6.D1 (n=32) | -0.8 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Change from Bsl - C7.D1 (n=29) | -0.8 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Change from Bsl - C8.D1 (n=26) | -0.7 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Change from Bsl - C9.D1 (n=25) | -0.5 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Change from Bsl - C10.D1 (n=22) | -0.7 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Change from Bsl - C11.D1 (n=21) | -1.2 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Change from Bsl - C12.D1 (n=18) | -0.8 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Change from Bsl - C13.D1 (n=17) | -1.2 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Change from Bsl - C14.D1 (n=17) | -1.3 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Change from Bsl - C15.D1 (n=12) | -1.1 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Change from Bsl - EOT (n=37) | -0.3 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) | Change from Bsl - C16.D1 (n=12) | -0.5 scores on a scale |
Secondary
Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G)
The questionnaire assesses pain intensity (worst, least, average, and right now), level of relief in the last 24 hours, and the impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). The pain interference index score (to measure how much pain had interfered with daily activities) was derived from Questions 7A-7G with a range from 0 (no interference) to 10 (completely interferes); higher scores indicate more interference.
Time frame: Baseline (C1.D1), Day 1 of Cycles 2 through 16, and End of Treatment (EOT=following Cycle 16 or within 7 days of withdrawal from study)
Population: PRO evaluable population; (n)=number of participants with evaluable data at observation.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Bsl mean C1.D1 (n=48) | 1.8 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Change from Bsl - C2.D1 (n=41) | -0.7 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Change from Bsl - C3.D1 (n=34) | -0.8 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Change from Bsl - C4.D1 (n=30) | -0.5 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Change from Bsl - C5.D1 (n=31) | -0.7 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Change from Bsl - C6.D1 (n=32) | -0.6 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Change from Bsl - C7.D1 (n=29) | -0.4 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Change from Bsl - C8.D1 (n=26) | -0.5 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Change from Bsl - C9.D1 (n=24) | -0.5 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Change from Bsl - C10.D1 (n=21) | -0.4 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Change from Bsl - C11.D1 (n=21) | -0.7 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Change from Bsl - C12.D1 (n=18) | -0.8 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Change from Bsl - C13.D1 (n=17) | -1.2 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Change from Bsl - C14.D1 (n=17) | -1.4 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Change from Bsl - C15.D1 (n=12) | -1.0 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Change from Bsl - C16.D1 (n=12) | -0.5 scores on a scale |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) | Change from Bsl - EOT (n=36) | -0.4 scores on a scale |
Secondary
Duration of PSA Response (DPR)
Defined as time from first documentation of PSA response (≥50% decrease in PSA from baseline that is subsequently confirmed) to first documentation of PSA progression (defined for patients with a PSA response as a 50% increase over nadir \[lowest\] and increase in absolute-value PSA level by at least 5 ng/mL \[or back to baseline\] and for patients without a PSA response as a 25% increase over baseline \[or nadir / lowest\] and increase in absolute-value PSA level by at least 5 ng/mL, both confirmed by a second value). Calculated as (end date for DPR - first PSA response + 1)/7.
Time frame: Baseline to first documentation of PSA progression up to 28 days after date of last dose
Population: ITT; DPR only calculated for the subgroup of patients with PSA response rate.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Duration of PSA Response (DPR) | 39.1 weeks |
Secondary
Percentage of Participants With Objective Response Rate (ORR)
Defined as confirmed complete response (CR: disappearance of all target lesions) or confirmed partial response (PR: ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD) according to response evaluation criteria in solid tumors (RECIST). Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
Time frame: Baseline to first documentation of PSA progression up to 28 days after date of last dose
Population: ITT; N=participants with measurable disease at baseline, received at least 1 dose of study medication, and had correct histological cancer type.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Percentage of Participants With Objective Response Rate (ORR) | 42.4 percentage of participants |
Secondary
Preliminary Assessment of PSA Modulation by SU011248
PSA modulation analyzed by the mean change in PSA response measured as ng/mL.
Time frame: Baseline to Day 28
Population: ITT population; PSA modulation was listed as a secondary endpoint for Phase 2, however, modulation was planned for analysis only for Phase 1 portion of the study. No formal analysis was completed to determine modulation.
Secondary
Ratio to Baseline (Bsl) in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFC
Soluble protein biomarker Vascular Endothelial Growth Factor C (VEGFC) measured as picograms per milliliter (pg/mL). PSA responders are participants with a confirmed PSA response as per the Working Group criteria (\>50% decrease from baseline) and non-responders are those not meeting the definition of responder. Ratio=value of soluble protein biomarkers at each time point to the value at baseline (C1D14 : C1D1).
Time frame: Baseline (Cycle 1 Day 1 [C1.D1]), C1.D14, C2.D1, C2.D14, C3.D1, C3.D14
Population: ITT
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline (Bsl) in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFC | Bsl median - PSA responder | 622.70 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline (Bsl) in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFC | Bsl median - PSA non-responder | 639.70 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline (Bsl) in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFC | C1D14 : C1D1 - PSA responder | 1.06 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline (Bsl) in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFC | C1D14 : C1D1 - PSA non-responder | 1.07 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline (Bsl) in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFC | C2.D1 : C1D1 - PSA responder | 0.88 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline (Bsl) in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFC | C2.D1 : C1D1 - PSA non-responder | 0.93 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline (Bsl) in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFC | C2.D14 : C1D1 - PSA responder | 0.92 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline (Bsl) in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFC | C2.D14 : C1D1 - PSA non-responder | 0.95 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline (Bsl) in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFC | C3.D1 : C1D1 - PSA responder | 1.51 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline (Bsl) in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFC | C3.D14 : C1D1 - PSA responder | 0.97 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline (Bsl) in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFC | C3.D14 : C1D1 - PSA non-responder | 0.96 pg/mL |
Comparison: C1D14 : C1D1p-value: 0.942Wilcoxon rank-sum test
Comparison: C2.D1 : C1D1p-value: 0.323Wilcoxon rank-sum test
Comparison: C2.D14 : C1D1p-value: 0.865Wilcoxon rank-sum test
Comparison: C3.D14 : C1D1p-value: 0.873Wilcoxon rank-sum test
Secondary
Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFC
Soluble protein biomarker VEGFC measured as pg/mL. CBR defined as confirmed CR (disappearance of all target lesions) or confirmed PR (≥30% decrease in sum of longest dimensions \[LD\] of target lesions taking as reference the baseline sum LD) or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) ≥3 months versus PD (≥20% increase in sum LD of target lesions taking as reference the smallest sum LD recorded since treatment started, unequivocal progression of existing non-target lesions, or appearance of ≥1 new lesions) or SD \<3 months.
Time frame: Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D14
Population: ITT
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFC | Bsl median - CR or PR | 581.05 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFC | Bsl median - SD or PD | 586.85 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFC | C1D14 : C1D1 - CR or PR | 1.21 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFC | C1D14 : C1D1 - SD or PD | 1.19 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFC | C2.D1 : C1D1 - CR or PR | 0.89 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFC | C2.D1 : C1D1 - SD or PD | 1.15 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFC | C2.D14 : C1D1 - CR or PR | 0.92 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFC | C2.D14 : C1D1 - SD or PD | 0.97 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFC | C3.D14 : C1D1 - CR or PR | 0.88 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFC | C3.D14 : C1D1 - SD or PD | 0.59 pg/mL |
Comparison: C1D14 : C1D1p-value: 0.839Wilcoxon rank-sum test
Comparison: C2.D1 : C1D1p-value: 0.219Wilcoxon rank-sum test
Comparison: C2.D14 : C1D1p-value: 0.788Wilcoxon rank-sum test
Comparison: C3.D14 : C1D1p-value: 0.164Wilcoxon rank-sum test
Secondary
Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR2
Soluble protein biomarker VEGFR2 measured as pg/mL. CBR defined as confirmed CR (disappearance of all target lesions) or confirmed PR (≥30% decrease in sum of longest dimensions \[LD\] of target lesions taking as reference the baseline sum LD) or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) ≥3 months versus PD (≥20% increase in sum LD of target lesions taking as reference the smallest sum LD recorded since treatment started, unequivocal progression of existing non-target lesions, or appearance of ≥1 new lesions) or SD \<3 months.
Time frame: Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D14
Population: ITT
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR2 | Bsl median - CR or PR | 9837.50 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR2 | Bsl median - SD or PD | 9484.25 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR2 | C1D14 : C1D1 - CR or PR | 0.73 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR2 | C1D14 : C1D1 - SD or PD | 0.75 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR2 | C2.D1 : C1D1 - CR or PR | 0.83 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR2 | C2.D1 : C1D1 - SD or PD | 0.83 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR2 | C2.D14 : C1D1 - CR or PR | 0.68 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR2 | C2.D14 : C1D1 - SD or PD | 0.60 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR2 | C3.D14 : C1D1 - CR or PR | 0.63 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR2 | C3.D14 : C1D1 - SD or PD | 0.80 pg/mL |
Comparison: C1D14 : C1D1p-value: 0.656Wilcoxon rank-sum test
Comparison: C2.D1 : C1D1p-value: 0.628Wilcoxon rank-sum test
Comparison: C2.D14 : C1D1p-value: 0.42Wilcoxon rank-sum test
Comparison: C3.D14 : C1D1p-value: 0.296Wilcoxon rank-sum test
Secondary
Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR3
Soluble protein biomarker VEGFR3 measured as pg/mL. CBR defined as confirmed CR (disappearance of all target lesions) or confirmed PR (≥30% decrease in sum of longest dimensions \[LD\] of target lesions taking as reference the baseline sum LD) or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) ≥3 months versus PD (≥20% increase in sum LD of target lesions taking as reference the smallest sum LD recorded since treatment started, unequivocal progression of existing non-target lesions, or appearance of ≥1 new lesions) or SD \<3 months.
Time frame: Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D14
Population: ITT
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR3 | Bsl median - CR or PR | 19975.00 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR3 | Bsl median - SD or PD | 22495.00 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR3 | C1D14 : C1D1 - CR or PR | 0.72 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR3 | C1D14 : C1D1 - SD or PD | 0.68 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR3 | C2.D1 : C1D1 - CR or PR | 0.78 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR3 | C2.D1 : C1D1 - SD or PD | 0.83 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR3 | C2.D14 : C1D1 - CR or PR | 0.69 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR3 | C2.D14 : C1D1 - SD or PD | 0.80 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR3 | C3.D14 : C1D1 - CR or PR | 0.61 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR3 | C3.D14 : C1D1 - SD or PD | 0.78 pg/mL |
Comparison: C1D14 : C1D1p-value: 0.903Wilcoxon rank-sum test
Comparison: C2.D1 : C1D1p-value: 0.434Wilcoxon rank-sum test
Comparison: C2.D14 : C1D1p-value: 0.687Wilcoxon rank-sum test
Comparison: C3.D14 : C1D1p-value: 0.296Wilcoxon rank-sum test
Secondary
Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR2
Soluble protein biomarker Vascular Endothelial Growth Factor receptor 2 (VEGFR2) measured as pg/mL. PSA responders are participants with a confirmed PSA response as per the Working Group criteria (\>50% decrease from baseline) and non-responders are those not meeting the definition of responder. Ratio=value of soluble protein biomarkers at each time point to the value at baseline (C1D14 : C1D1).
Time frame: Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D1, C3.D14
Population: ITT
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR2 | Bsl median - PSA responder | 9889.00 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR2 | Bsl median - PSA non-responder | 10324.00 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR2 | C1D14 : C1D1 - PSA responder | 0.73 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR2 | C1D14 : C1D1 - PSA non-responder | 0.68 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR2 | C2.D1 : C1D1 - PSA responder | 0.80 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR2 | C2.D1 : C1D1 - PSA non-responder | 0.79 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR2 | C2.D14 : C1D1 - PSA responder | 0.67 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR2 | C2.D14 : C1D1 - PSA non-responder | 0.60 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR2 | C3.D1 : C1D1 - PSA responder | 0.81 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR2 | C3.D14 : C1D1 - PSA responder | 0.63 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR2 | C3.D14 : C1D1 - PSA non-responder | 0.67 pg/mL |
Comparison: C1D14 : C1D1p-value: 0.736Wilcoxon rank-sum test
Comparison: C2.D1 : C1D1p-value: 0.962Wilcoxon rank-sum test
Comparison: C2.D14 : C1D1p-value: 0.185Wilcoxon rank-sum test
Comparison: C3.D14 : C1D1p-value: 1Wilcoxon rank-sum test
Secondary
Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR3
Soluble protein biomarker Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) measured as picograms per milliliter (pg/mL). PSA responders are participants with a confirmed PSA response as per the Working Group criteria (\>50% decrease from baseline) and non-responders are those not meeting the definition of responder. Ratio=value of soluble protein biomarkers at each time point to the value at baseline (C1D14 : C1D1).
Time frame: Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D1, C3.D14
Population: ITT
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR3 | Bsl median - PSA responder | 22475.00 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR3 | Bsl median - PSA non-responder | 22070.00 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR3 | C1D14 : C1D1 - PSA responder | 0.69 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR3 | C1D14 : C1D1 - PSA non-responder | 0.73 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR3 | C2.D1 : C1D1 - PSA responder | 0.75 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR3 | C2.D1 : C1D1 - PSA non-responder | 0.75 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR3 | C2.D14 : C1D1 - PSA responder | 0.65 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR3 | C2.D14 : C1D1 - PSA non-responder | 0.72 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR3 | C3.D1 : C1D1 - PSA responder | 0.65 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR3 | C3.D14 : C1D1 - PSA responder | 0.56 pg/mL |
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR3 | C3.D14 : C1D1 - PSA non-responder | 0.66 pg/mL |
Comparison: C1D14 : C1D1p-value: 0.386Wilcoxon rank-sum test
Comparison: C2.D1 : C1D1p-value: 0.904Wilcoxon rank-sum test
Comparison: C2.D14 : C1D1p-value: 0.812Wilcoxon rank-sum test
Comparison: C3.D14 : C1D1p-value: 0.49Wilcoxon rank-sum test
Secondary
Time to PSA Progression
Defined as the time from start of study treatment to first documentation of PSA progression using the PSA Working Group criteria calculated as (first event date - first dose date + 1)/7. PSA progression is defined for patients with a PSA response, as a 50% increase over nadir (lowest) and increase in absolute-value PSA level by at least 5 nanograms per milliliter (ng/mL) \[or back to baseline\] and for patients without a PSA response as a 25% increase over baseline \[or nadir (lowest)\] and increase in absolute-value PSA level by at least 5 ng/mL, both confirmed by a second value.
Time frame: Baseline to first documentation of PSA progression up to 28 days after date of last dose
Population: ITT
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | Time to PSA Progression | 42.1 weeks |