Pazopanib, Docetaxel, Prednisone Prostate

NCT ID: NCT01385228

Last Updated: 2018-06-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2016-02-29

Brief Summary

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).

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Pazopanib

Intervention Type: DRUG

Dose Level "Xa" - daily administration of pazopanib on days 1 through 21 starting at 400mg with a maximum dose of 1000mg.

Docetaxel

Intervention Type: DRUG

Docetaxel given IV on Day 1 starting dose 60mg/m2 increase to 75mg/m2

Prednisone

Intervention Type: DRUG

5mg Prednisone given twice daily days 1-21.

Pegfilgrastim

Intervention Type: DRUG

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.

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Docetaxel given IV on Day 1 starting dose 60mg/m2 increase to 75mg/m2

Pazopanib

Intervention Type: DRUG

Dose Level "Xb" - daily administration of pazopanib on days 3 through 19 starting at 400mg with a maximum dose of 1000mg.

Prednisone

Intervention Type: DRUG

5mg Prednisone given twice daily days 1-21.

Pegfilgrastim

Intervention Type: DRUG

Interventions

Pazopanib

Dose Level "Xa" - daily administration of pazopanib on days 1 through 21 starting at 400mg with a maximum dose of 1000mg.

Intervention Type: DRUG

Docetaxel

Docetaxel given IV on Day 1 starting dose 60mg/m2 increase to 75mg/m2

Intervention Type: DRUG

Pazopanib

Dose Level "Xb" - daily administration of pazopanib on days 3 through 19 starting at 400mg with a maximum dose of 1000mg.

Intervention Type: DRUG

Prednisone

5mg Prednisone given twice daily days 1-21.

Intervention Type: DRUG

Pegfilgrastim

Intervention Type: DRUG

Other Intervention Names

Pazopanib (GW786034); Taxotere; Pazopanib (GW786034); Neulasta

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Daniel George, MD

OTHER

Sponsor Role: lead

Responsible Party

Daniel George, MD

Associate Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Daniel J George, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Cancer Institute

Locations

The University of Chicago

Chicago, Illinois, United States

Duke Cancer Institute

Durham, North Carolina, United States

Countries

United States

Other Identifiers

PZP113296

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

c09-039

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00026577

Identifier Type: -

Identifier Source: org_study_id