Pazopanib, Docetaxel, Prednisone Prostate

• Register: ClinicalTrials.gov
• Last refreshed on: 10 December 2012
• Main ID: NCT01385228
• Date of registration: 12/06/2011
• Primary sponsor: Daniel George
• Public title: Pazopanib, Docetaxel, Prednisone Prostate
• Scientific title: Phase I/II Study of Docetaxel, Prednisone and Pazopanib in Men With Metastatic Castrate-Resistant Prostate Cancer (mCRPC) and Poor-Risk Factors
• Date of first enrolment: June 2011
• Target sample size: 122
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01385228
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Carol Winters, RN

• Name: Daniel J George, MD
• Affiliation: Duke Cancer Institute

Key inclusion & exclusion 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 4 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.

- 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) > 10% 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Male

Health Condition(s) or Problem(s) studied

Prostate Cancer

Intervention(s)

Drug: Docetaxel

Drug: Pazopanib

Drug: Prednisone

Primary Outcome(s)

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]

Secondary Outcome(s)

Compare circulating tumor cell (CTC) levels of participants receiving pazopanib, docetaxel, prednisone versus docetaxel and prednisone alone. [Time Frame: 3 years]

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]

Compare PSA kinetics in the docetaxel, prednisone and pazopanib arm versus docetaxel, prednisone alone. [Time Frame: 3 years]

Compare serum biomarkers of angiogenesis for participants receiving pazopanib, docetaxel, prednisone versus docetaxel and prednisone. [Time Frame: 3 years]

Determine the objective response rates of participants. [Time Frame: 4 years]

Determine the overall survival of participants. [Time Frame: 4 years]

Establish the maximum tolerated dose [Time Frame: 2 years]

Measurement of pazopanib and docetaxel drug levels in participants. [Time Frame: 2 years]

Relationship between genetic variants and drug levels (Cmax, Tmax, AUC, CL, Vd). [Time Frame: 2 years]

Secondary ID(s)

c09-039

Pro00026577

PZP113296

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

GlaxoSmithKline