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Phase I/II Study of Docetaxel, Prednisone and Pazopanib in Men With Metastatic Castrate-Resistant Prostate Cancer (mCRPC) and Poor-Risk Factors


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Male
Prostate Cancer

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Trial Information

Phase I/II Study of Docetaxel, Prednisone and Pazopanib in Men With Metastatic Castrate-Resistant Prostate Cancer (mCRPC) and Poor-Risk Factors


This Phase I/II 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 tolerated with 0-1 Dose Limiting Toxicity (DLT)
experienced in six patients. Patients from all risk strata will be allowed onto the Phase I
portion.

Once the MTD is established the investigators will perform a randomized Phase II study in
men with intermediate or poor risk CRPC. Clinical efficacy in this patient population will
be compared to that of patients treated with DPP to DP for PFS, overall survival (OS),
objective response rates (ORR), Prostate Specific Antigen (PSA) kinetics and pain response.
Patients will be treated for up to a maximum of 1 year with the combination, after which
patients will be allowed to continue on pazopanib alone.


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.

- 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

Type of Study:

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

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

Outcome Description:

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. 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.

Outcome Time Frame:

3 years

Safety Issue:

Yes

Principal Investigator

Daniel J George, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

Pro00026577

NCT ID:

NCT01385228

Start Date:

June 2011

Completion Date:

December 2016

Related Keywords:

  • Prostate Cancer
  • prostate cancer
  • metastatic
  • pazopanib
  • docetaxel
  • metastatic prostate cancer
  • Prostatic Neoplasms

Name

Location

Duke Cancer Institute Durham, North Carolina  27710
The University of Chicago Chicago, Illinois  60637