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A Randomized, Phase II Study of GW786034 (Pazopanib) in Stage D0 Relapsed Androgen Sensitive Prostate Cancer Following Limited GnRH Agonist Therapy


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

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Trial Information

A Randomized, Phase II Study of GW786034 (Pazopanib) in Stage D0 Relapsed Androgen Sensitive Prostate Cancer Following Limited GnRH Agonist Therapy


PRIMARY OBJECTIVES:

I. Determine if pazopanib hydrochloride is able to increase time to progression, as measured
by prostate-specific antigen (PSA), after 6 months of limited gonadotropin-releasing hormone
(GnRH) agonist therapy comprising leuprolide acetate or goserelin in patients with
androgen-sensitive relapsed stage D0 prostate cancer.

SECONDARY OBJECTIVES:

I. Determine the adverse events in patients treated with this regimen. II. To monitor for
changes in testosterone in relationship to pazopanib therapy versus observation.

OUTLINE:

Patients receive androgen blockade comprising GnRH agonist therapy (e.g., leuprolide acetate
or goserelin acetate) for 6 months. Patients who develop metastases or have PSA progression
while on GnRH agonist therapy are removed from the study and placed on total androgen
blockade. The remaining patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28.
Treatment repeats every 28 days in the absence of disease progression or unacceptable
toxicity.

ARM II: Patients undergo observation.

After completion of study treatment, patients are followed up periodically for up to 12
months.


Inclusion Criteria:



- Histologically or cytologically confirmed prostate cancer

- Stage D0

- Must have undergone some definitive local therapy for prostate cancer

- Must be free of macrometastatic disease, as evidenced by computed tomography (CT)
scan and bone scan, if serum PSA ≥ 10 ng/mL prior to GnRH agonist therapy

- Progressive disease meeting the following criteria: NOTE: Patients who have undergone
a prostatectomy and have two detectable, rising serum PSA levels are eligible

- Two consecutive rises in PSA above nadir recorded after definite local therapy

- Serum PSA concentrations must have absolute value of > 0.5 ng/mL (separated by ≥
2 weeks) prior to beginning GnRH agonist therapy

- PSA < 0.5 ng/mL

- Testosterone < 30 ng/mL

- No measurable disease

- No brain metastases requiring steroid or anticonvulsant therapy

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS
60- 100%

- Prothrombin time (PT)/international normalization ratio (INR)/partial thromboplastin
time (PTT) ≤ 1.2 times upper limit of normal (ULN)

- Bilirubin normal

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN

- Creatinine ≤ 1.5 times ULN OR creatinine clearance > 50 mL/min

- Proteinuria ≤ 1+ on 2 consecutive dipsticks > 1 week apart

- Urine protein: creatinine ratio < 1 OR urine protein < 1.0 g/24 hours

- Fertile patients must use effective double-barrier contraception during study therapy
OR completely abstain from sexual intercourse 14 days prior to, during, and for ≥ 21
days after completion of study therapy

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to pazopanib hydrochloride or to other agents used in the
study

- No concurrent uncontrolled illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Psychiatric illness or social situations that would preclude compliance with
study requirements

- No human immunodeficiency virus (HIV) positivity

- No condition that impairs the ability to swallow and retain pazopanib hydrochloride
tablets, including any of the following:

- Gastrointestinal tract disease resulting in an inability to take oral medication

- Requirement for intravenous (IV) alimentation

- Prior surgical procedures affecting absorption

- Active peptic ulcer disease

- No other conditions, including any of the following:

- Serious or nonhealing wound, ulcer, or bone fracture

- Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
within the past 28 days

- Cerebrovascular accident within the past 6 months

- Myocardial infarction, admission for unstable angina, cardiac angioplasty, or
stenting within the past 6 months

- Venous thrombosis within the past 12 weeks

- New York Heart Association (NYHA) class III or IV heart failure

- History of currently treated asymptomatic NYHA class II heart failure
allowed

- Systolic blood pressure (BP) ≤ 140 mm Hg and diastolic BP ≤ 90 mm Hg

- Prior initiation or adjustment of BP medication allowed provided that the
average of 3 BP readings at a visit prior to enrollment is < 140/90 mm Hg

- More than 3 months since prior antiandrogen

- More than 4 months since prior orchiectomy or implantable luteinizing LHRH agonist

- No prior GnRH agonists except for neoadjuvant or adjuvant therapy associated with
local therapy

- Patients who have started a GnRH agonist for micrometastatic disease after local
therapy allowed provided the following criteria are met:

- Progressive disease

- Willing to discontinue therapy before 6 months have elapsed

- Have signed consent prior to completing 6 months of the initial hormone
therapy

- Are within 4 months of initiating GnRH agonist therapy

- No prior or concurrent GnRH antagonist therapy

- No concurrent ketoconazole

- No concurrent cytochrome P450 2C9 (CYP2C9) substrates, including any of the
following:

- Anticoagulants (e.g., warfarin [therapeutic doses only])

- Low molecular weight heparin or prophylactic low-dose warfarin allowed

- Oral hypoglycemics (e.g., glipizide, glyburide, tolbutamide, glimepiride, or
nateglinide)

- Ergot derivatives (e.g., dihydroergotamine, ergonovine, ergotamine, or
methylergonovine)

- Neuroleptics (e.g., pimozide)

- Erectile dysfunction agents (e.g., sildenafil, tadalafil, or vardenafil)

- Antiarrhythmics (e.g., bepridil, flecainide, lidocaine, mexiletin, amiodarone,
quinidine, or propafenone)

- Immune modulators (e.g., cyclosporine, tacrolimus, or sirolimus)

- Miscellaneous medications (e.g., theophylline, quetiapine, risperidone, tacrine,
clozapine, or atomoxetine)

- No concurrent medications associated with the risk of QTc prolongation and/or
Torsades de Pointes

- Replacement of drugs that do not carry these risks allowed

- No other concurrent non-Food and Drug Administration (FDA)-approved agents

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Time to PSA progression

Outcome Description:

The time to disease progression distributions between the therapy and observation groups will be estimated using the Kaplan-Meier estimate, and compared using the log-rank test.

Outcome Time Frame:

Baseline, every 4 weeks during treatment, and up to 12 months after completion of study treatment

Safety Issue:

No

Principal Investigator

Edwin Posadas

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00202

NCT ID:

NCT00454571

Start Date:

June 2006

Completion Date:

Related Keywords:

  • Recurrent Prostate Cancer
  • Prostatic Neoplasms

Name

Location

University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470