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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00137436
First received: August 26, 2005
Last updated: August 25, 2011
Last verified: August 2011
  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 1
Phase 2

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:


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).

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
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
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014