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
  Purpose

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).


Condition Intervention Phase
Prostate Cancer
Drug: Pazopanib
Drug: Docetaxel
Drug: Prednisone
Drug: Pegfilgrastim
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Docetaxel, Prednisone and Pazopanib in Men With Metastatic Castrate-Resistant Prostate Cancer (mCRPC) and Poor-Risk Factors

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 36
Study Start Date: June 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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: Prednisone
5mg Prednisone given twice daily days 1-21.
Other Name: Prednisone
Drug: Pegfilgrastim
Other Name: Neulasta
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.
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

Detailed Description:

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.

  Eligibility

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

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
  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: NCT01385228

Contacts
Contact: Carol Winters, RN (919)668-8577

Locations
United States, Illinois
The University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Elia Martinez, RN    773-702-3623      
Principal Investigator: Russell Szmulewitz, MD         
United States, North Carolina
Duke Cancer Institute Recruiting
Durham, North Carolina, United States, 27710
Contact: Carol Winters, RN    919-668-8577      
Principal Investigator: Andrew Armstrong, MD, ScM         
Sponsors and Collaborators
Daniel George
GlaxoSmithKline
Investigators
Principal Investigator: Daniel J George, MD Duke Cancer Institute
  More Information

No publications provided

Responsible Party: Daniel George, Associate Professor of Medicine, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01385228     History of Changes
Other Study ID Numbers: Pro00026577, PZP113296, c09-039
Study First Received: June 12, 2011
Last Updated: March 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
prostate cancer
metastatic
pazopanib
docetaxel
metastatic prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Docetaxel
Prednisone
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on October 19, 2014