Clinical trial NCT00454571 (phase 2, status: completed)
Conditions: recurrent prostate cancer
ICD codes: C61, D29.1, D40.0, Z15.03, Z80.42, Z85.46, Z12.5
Drugs: pazopanib hydrochloride, leuprolide acetate, goserelin acetate
SMILES: CN(C1=CC2=NN(C)C(C)=C2C=C1)C1=CC=NC(NC2=CC=C(C)C(=C2)S(N)(=O)=O)=N1, CC(C)C[C@H](NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=CC=CC=C12)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)NNC(N)=O, CC(C)C[C@H](NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=CC=CC=C12)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)NNC(N)=O
Eligibility criteria:

        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