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Pazopanib, Docetaxel, Prednisone Prostate

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Duke University
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Daniel George, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01385228
First received: June 12, 2011
Last updated: March 11, 2014
Last verified: March 2014

June 12, 2011
March 11, 2014
June 2011
December 2015   (final data collection date for primary outcome measure)
Number and Percent of Participants with Adverse Events as a Measure of Safety and Tolerability; Number and Percent of participants who have disease progression [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
The primary objective for the phase I study is to assess the safety and tolerability of pazopanib, docetaxel, and prednisone given in combination in patients with metastatic castration resistant prostate cancer.
  • Number and Percent of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    The primary objective for the phase I study is to assess the safety and tolerability of pazopanib, docetaxel, and prednisone given in combination in patients with metastatic castration resistant prostate cancer.
  • Number and percent of participants who have disease progression. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    The primary objective for the phase II study is to measure the anti-tumor activity of pazopanib, docetaxel and prednisone compared to placebo, docetaxel and prednisone as assessed by progression free survival.
Complete list of historical versions of study NCT01385228 on ClinicalTrials.gov Archive Site
  • Establish the maximum tolerated dose [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Determine the dose levels of pazopanib and docetaxel that are the most tolerated.
  • Measurement of pazopanib and docetaxel drug levels in participants. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Measure the drug levels (pharmacokinetics) of pazopanib and docetaxel in the system will be assessed by the peak drug concentration (Cmax), time of peak concentration (Tmax), terminal elimination rate constant (kel), area under the drug concentration curve (AUC), total body clearance (CL), and the volume of distribution for docetaxel (Vd).
  • Relationship between genetic variants and drug levels (Cmax, Tmax, AUC, CL, Vd). [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Determine whether genetic variants impact the pharmacokinetics of pazopanib.
  • Establish the optimal dosing schedule [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Establish the optimal dosing schedule for the combination of docetaxel, prednisone and pazopanib
  • Establish the maximum tolerated dose [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Determine the dose levels of pazopanib and docetaxel that are the most tolerated and continue on to the phase II study.
  • Measurement of pazopanib and docetaxel drug levels in participants. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Measure the drug levels (pharmacokinetics) of pazopanib and docetaxel in the system will be assessed by the peak drug concentration (Cmax), time of peak concentration (Tmax), terminal elimination rate constant (kel), area under the drug concentration curve (AUC), total body clearance, and the volume of distribution for docetaxel.
  • Relationship between genetic variants and drug levels (Cmax, Tmax, AUC, CL, Vd). [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Determine whether genetic variants impact the pharmacokinetics of pazopanib.
  • Determine the objective response rates of participants. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Determine response rates using RECIST 1.1 and PCWG2 criteria and compare to placebo arm.
  • Determine the overal surival of participants. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Compare overall survival in the docetaxel, pazopanib, prednisone arm compared to the docetaxel, prednisone, and placebo (control) arm.
  • Compare serum biomarkers of angiogenesis for participants receiving pazopanib, docetaxel, prednisone versus docetaxel and prednisone. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Exploratory angiogenic and cytokine markers, including VEGF and related growth factors will be measured and their association with outcome on the two study arms will be evaluated.
  • Compare circulating tumor cell levels of participants receiving pazopanib, docetaxel, prednisone versus docetaxel and prednisone alone. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Evaluate baseline CTC levels and changes in CTC in the two treatment arms.
  • Compare pain responses as measured by the modified brief pain inventory (mBPI) of participants receiving pazopanib, docetaxel, prednisone versus docetaxel and prednisone alone. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Compare PSA kinetics in the docetaxel, prednisone and pazopanib arm versus docetaxel, prednisone alone. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Describe the percent and number of patients with a 30% and 50% decrease in PSA on study in each arm.
Not Provided
Not Provided
 
Pazopanib, Docetaxel, Prednisone Prostate
Phase I Study of Docetaxel, Prednisone and Pazopanib in Men With Metastatic Castrate-Resistant Prostate Cancer (mCRPC) and Poor-Risk Factors

The primary purpose is to define the safety and tolerability of docetaxel/prednisone in combination with pazopanib (DPP) in men with metastatic Castration Resistant Prostate Cancer (mCRPC).

This Phase I study will consist of a dose escalation portion which includes a dose escalation phase of 10 dose levels: (1a) docetaxel 60 mg/m2, pazopanib 400 mg daily, prednisone 5 mg BID; (2a) docetaxel 75 mg/m2, pazopanib 400 mg daily, prednisone 5 mg BID; and (3a) docetaxel 75 mg/m2, pazopanib 600 mg daily, prednisone 5 mg BID; (4a) docetaxel 75mg/m2, pazopanib 800 mg daily, (5a) docetaxel 75mg/m2, pazopanib 1000mg daily, prednisone 5 mg; (1b) docetaxel 60 mg/m2, pazopanib 400 mg daily x 17 days, prednisone 5 mg BID; (2b) docetaxel 75 mg/m2, pazopanib 400 mg daily x 17 days, prednisone 5 mg BID; and (3b) docetaxel 75 mg/m2, pazopanib 600 mg daily x 17 days, prednisone 5 mg BID; (4b) docetaxel 75mg/m2, pazopanib 800 mg daily x 17 days, (5b) docetaxel 75mg/m2, pazopanib 1000mg daily x 17 days, prednisone 5 mg. If the investigators see > 1 dose limiting toxicity (DLT) at Dose level 3 then the investigators would investigate docetaxel 75 mg/m2, pazopanib 600 mg daily, prednisone 5 mg BID (Dose level 3a). If < 1 DLT are seen at Dose level 3 and Pharmacokinetic (PK) analysis is complete and acceptable, then the investigators will proceed to dose level 4) docetaxel 75 mg/m2, pazopanib 1000 mg daily, prednisone 5 mg BID.

The investigators will dose escalate in a classic 3+3 design. The maximum tolerated dose (MTD) will be defined as the highest dose level that does not result in 2 or more dose limiting toxicities (DLTs). A dose expansion at the MTD of 10-15 patients (up to a total of 36 patients) will be accrued in order to further describe the safety profile.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
  • Drug: Pazopanib
    Dose Level "Xa" - daily administration of pazopanib on days 1 through 21 starting at 400mg with a maximum dose of 1000mg.
    Other Name: Pazopanib (GW786034)
  • Drug: Docetaxel
    Docetaxel given IV on Day 1 starting dose 60mg/m2 increase to 75mg/m2
    Other Name: Taxotere
  • Drug: Pazopanib
    Dose Level "Xb" - daily administration of pazopanib on days 3 through 19 starting at 400mg with a maximum dose of 1000mg.
    Other Name: Pazopanib (GW786034)
  • Drug: Prednisone
    5mg Prednisone given twice daily days 1-21.
    Other Name: Prednisone
  • Drug: Pegfilgrastim
    Other Name: Neulasta
  • Experimental: Dose Level "Xa"
    once daily pazopanib for Days 1-21 in combination with docetaxel given IV on Day 1 and prednisone daily. Pegfilgrastim (Neulasta) every 21 days on Day 2, 3 or 4 of each cycle.
    Interventions:
    • Drug: Pazopanib
    • Drug: Docetaxel
    • Drug: Prednisone
    • Drug: Pegfilgrastim
  • Experimental: Dose Level "Xb"
    once daily oral administration of pazopanib for Days 3-19 in combination with docetaxel given intravenous administration on Day 1 and prednisone daily. Pegfilgrastim (Neulasta) every 21 days on Day 2, 3 or 4 of each cycle.
    Interventions:
    • Drug: Docetaxel
    • Drug: Pazopanib
    • Drug: Prednisone
    • Drug: Pegfilgrastim
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
36
December 2016
December 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically confirmed carcinoma of the prostate. Histologic evidence may be confirmed through local or metastatic biopsy review. Non-adenocarcinomas are permitted.
  • Radiographic evidence of metastatic disease; non-evaluable, bone only metastasis is permitted.
  • Evidence of disease progression despite castrate levels of testosterone (<50 ng/dl).
  • At the time of screening, at least 2 weeks since prior palliative radiation therapy and 4 weeks from major surgery, and resolution of all toxic effects of prior therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE); version 4.0 Grade < 1.
  • Age >18 years
  • Adequate laboratory parameters
  • Eastern Cooperative Oncology Group (ECOG) performance status between 0 and 2
  • Life expectancy greater than 3 months
  • Written, signed and dated Institutional Review Board (IRB) approved informed consent form.

Exclusion Criteria:

  • History of or active central nervous system metastases
  • The use of immunologic, biologic, or hormonal therapies within 2 weeks of study entry.
  • Major surgery, open biopsy, traumatic injury within 4 weeks of the screening visit
  • Subjects who have not recovered from prior biopsy, surgery, traumatic injury, and/or radiation therapy.
  • Previous treatment with docetaxel, including in the neo-adjuvant or adjuvant setting
  • Presence of non-healing wound or ulcer
  • Grade 3 or greater hemorrhage within the past month.
  • Uncontrolled hypertension
  • American Heart Association Class 2-4 heart disease or any history of congestive heart failure with an ejection fraction <40%, recent cardiovascular event (within 12 months) including unstable angina, any exertional angina, myocardial infarction, exertional or rest claudication, or stroke/Cerebral Vascular Event/Transient Ischemic Attack. Patients with known moderate to severe documented carotid or peripheral vascular disease are excluded. Angioplasty or stenting of coronary or peripheral arteries are exclusionary if within the past 12 months.
  • Anticoagulation with warfarin (therapeutic doses of warfarin for catheter patency are permitted up to 2 mg/day). Low molecular weight heparin is permitted.
  • Diabetes mellitus with glycosylated hemoglobin A1c (HbgA1c) > 8% despite therapy
  • Subjects with active autoimmune disorder(s) being treated with systemic immunosuppressive agents within 4 weeks prior to the screening visit.
  • Active infection(s), active antimicrobial therapy or serious intercurrent illness.
  • Does not agree to use medically acceptable contraceptive methods while on study and for 3 months after the last dose of pazopanib.
  • Any other major medical or psychiatric illness that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in this study, including inability to absorb oral medications.
  • Known hypersensitivity to any of the components in the docetaxel infusion or other medical reasons for not being able to receive adequate premedication (for example, antihistamine or anti-inflammatory agents).
  • CalculatedQT (QTc) interval on baseline EKG > 500milliseconds
  • History or presence of nephrotic syndrome
Male
18 Years and older
No
Contact: Carol Winters, RN (919)668-8577
United States
 
NCT01385228
Pro00026577, PZP113296, c09-039
No
Daniel George, Duke University Medical Center
Daniel George
GlaxoSmithKline
Principal Investigator: Daniel J George, MD Duke Cancer Institute
Duke University
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP