Study Of SU011248 In Combination With Docetaxel (Taxotere) And Prednisone In Patients With Prostate Cancer - Full Text View

Sponsor:	Pfizer
Information provided by (Responsible Party):	Pfizer
ClinicalTrials.gov Identifier:	NCT00137436

Purpose

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).

Condition	Intervention	Phase
Prostatic Neoplasms	Drug: Docetaxel Drug: Prednisone Drug: SU011248	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 1/2 Safety And Pharmacokinetic Study Of SU011248 In Combination With Docetaxel (Taxotere) And Prednisone In Patients With Metastatic Hormone Refractory Prostate Cancer (HRPC)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Prednisone Docetaxel Sunitinib malate Sunitinib

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

Percentage of Participants With Prostate Specific Antigen (PSA) Response [ Time Frame: Baseline, Day 1 of each 21-day cycle ] [ Designated as safety issue: No ]
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 Outcome Measures:

Time to PSA Progression [ Time Frame: Baseline to first documentation of PSA progression up to 28 days after date of last dose ] [ Designated as safety issue: No ]
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.
Duration of PSA Response (DPR) [ Time Frame: Baseline to first documentation of PSA progression up to 28 days after date of last dose ] [ Designated as safety issue: No ]
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) [ Time Frame: Baseline to first documentation of PSA progression up to 28 days after date of last dose ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline (Cycle 1 Day 1 [C1.D1]), C1.D14, C2.D1, C2.D14, C3.D1, C3.D14 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D1, C3.D14 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D1, C3.D14 ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D14 ] [ Designated as safety issue: No ]
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.
Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR2 [ Time Frame: Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D14 ] [ Designated as safety issue: No ]
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.
Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR3 [ Time Frame: Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D14 ] [ Designated as safety issue: No ]
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) [ 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) ] [ Designated as safety issue: No ]
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) [ 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) ] [ Designated as safety issue: No ]
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) [ 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) ] [ Designated as safety issue: No ]
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 [ Time Frame: Baseline to Day 28 ] [ Designated as safety issue: No ]
PSA modulation analyzed by the mean change in PSA response measured as ng/mL.

Enrollment:	93
Study Start Date:	October 2005
Study Completion Date:	March 2010
Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A SU011248 in combination with docetaxel and prednisone	Drug: Docetaxel 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). Other Name: Taxotere; Sunitinib malate; SUTENT Drug: Prednisone Prednisone Phase1/2 - 5 mg twice a day (BID), oral. Drug: SU011248 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).

Arms

Assigned Interventions

Experimental: A

SU011248 in combination with docetaxel and prednisone

Drug: Docetaxel

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).

Other Name: Taxotere; Sunitinib malate; SUTENT

Drug: Prednisone

Prednisone Phase1/2 - 5 mg twice a day (BID), oral.

Drug: SU011248

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).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00137436

Locations

United States, Illinois
Pfizer Investigational Site
Harvey, Illinois, United States, 60426
Pfizer Investigational Site
Tinley Park, Illinois, United States, 60477
United States, Indiana
Pfizer Investigational Site
Hobart, Indiana, United States, 46342
Pfizer Investigational Site
Munster, Indiana, United States, 46321
United States, North Carolina
Pfizer Investigational Site
Durham, North Carolina, United States, 27710
United States, Oregon
Pfizer Investigational Site
Portland, Oregon, United States, 97239
Pfizer Investigational Site
Portland, Oregon, United States, 97239-3098
United States, South Carolina
Pfizer Investigational Site
Myrtle Beach, South Carolina, United States, 29572
United States, Tennessee
Pfizer Investigational Site
Clarksville, Tennessee, United States, 37043
Pfizer Investigational Site
Franklin, Tennessee, United States, 37067
Pfizer Investigational Site
Gallarin, Tennessee, United States, 37066
Pfizer Investigational Site
Hermitage, Tennessee, United States, 37076
Pfizer Investigational Site
Lebanon, Tennessee, United States, 37087
Pfizer Investigational Site
Murfreesboro, Tennessee, United States, 37130
Pfizer Investigational Site
Nashville, Tennessee, United States, 37203
Pfizer Investigational Site
Nashville, Tennessee, United States, 37205
Pfizer Investigational Site
Nashville, Tennessee, United States, 37207
Pfizer Investigational Site
Nashville, Tennessee, United States, 37211
Pfizer Investigational Site
Smithville, Tennessee, United States, 37166
Pfizer Investigational Site
Smyrna, Tennessee, United States, 37167
Pfizer Investigational Site
Tullahoma, Tennessee, United States, 37388
United States, Texas
Pfizer Investigational Site
Dallas, Texas, United States, 75246
Pfizer Investigational Site
Houston, Texas, United States, 77030
United States, Wisconsin
Pfizer Investigational Site
Madison, Wisconsin, United States, 53792

Sponsors and Collaborators

Pfizer

Investigators

Study Director:

Pfizer CT.gov Call Center

Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT00137436 History of Changes
Other Study ID Numbers:	A6181043
Study First Received:	August 26, 2005
Results First Received:	May 28, 2009
Last Updated:	August 25, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Pfizer:

First-line treatment of metastatic hormone-refractory prostate cancer SUTENT in combination with docetaxel and prednisone

Additional relevant MeSH terms:

Neoplasms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Prednisone
Docetaxel
Sunitinib
Glucocorticoids
Hormones

Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anti-Inflammatory Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012