Study Of SU011248 In Combination With Docetaxel (Taxotere) And Prednisone In Patients With Prostate Cancer

Prostatic Neoplasms Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00137436
• Other study ID #: A6181043
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 26, 2005
• Last updated: August 25, 2011
• Start date: October 2005
• Est. completion date: March 2010

Study information

• Verified date: August 2011
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: March 2010
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Pfizer Investigational Site	Clarksville	Tennessee
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Durham	North Carolina
United States	Pfizer Investigational Site	Franklin	Tennessee
United States	Pfizer Investigational Site	Gallarin	Tennessee
United States	Pfizer Investigational Site	Harvey	Illinois
United States	Pfizer Investigational Site	Hermitage	Tennessee
United States	Pfizer Investigational Site	Hobart	Indiana
United States	Pfizer Investigational Site	Houston	Texas
United States	Pfizer Investigational Site	Lebanon	Tennessee
United States	Pfizer Investigational Site	Madison	Wisconsin
United States	Pfizer Investigational Site	Munster	Indiana
United States	Pfizer Investigational Site	Murfreesboro	Tennessee
United States	Pfizer Investigational Site	Myrtle Beach	South Carolina
United States	Pfizer Investigational Site	Nashville	Tennessee
United States	Pfizer Investigational Site	Nashville	Tennessee
United States	Pfizer Investigational Site	Nashville	Tennessee
United States	Pfizer Investigational Site	Nashville	Tennessee
United States	Pfizer Investigational Site	Portland	Oregon
United States	Pfizer Investigational Site	Portland	Oregon
United States	Pfizer Investigational Site	Smithville	Tennessee
United States	Pfizer Investigational Site	Smyrna	Tennessee
United States	Pfizer Investigational Site	Tinley Park	Illinois
United States	Pfizer Investigational Site	Tullahoma	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline, Day 1 of each 21-day cycle	No
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.	Baseline to first documentation of PSA progression up to 28 days after date of last dose	No
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.	Baseline to first documentation of PSA progression up to 28 days after date of last dose	No
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.	Baseline to first documentation of PSA progression up to 28 days after date of last dose	No
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).	Baseline (Cycle 1 Day 1 [C1.D1]), C1.D14, C2.D1, C2.D14, C3.D1, C3.D14	No
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).	Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D1, C3.D14	No
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).	Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D1, C3.D14	No
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.	Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D14	No
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.	Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D14	No
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.	Baseline (C1.D1), C1.D14, C2.D1, C2.D14, C3.D14	No
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.	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)	No
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.	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)	No
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.	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)	No
Secondary	Preliminary Assessment of PSA Modulation by SU011248	PSA modulation analyzed by the mean change in PSA response measured as ng/mL.	Baseline to Day 28	No

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