Clinical trial NCT00454571: Pazopanib Hydrochloride After Leuprolide Acetate or Goserelin Acetate in Treating Patients With Relapsed Prostate Cancer
Official title: A Randomized, Phase II Study of GW786034 (Pazopanib) in Stage D0 Relapsed Androgen Sensitive Prostate Cancer Following Limited GnRH Agonist Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Prostate Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-03-30
Enrollment: 37
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized phase II trial is studying how well pazopanib hydrochloride works after leuprolide or goserelin in treating patients with relapsed prostate cancer. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as leuprolide acetate or goserelin acetate, may lessen the amount of androgens made by the body. Giving pazopanib after leuprolide or goserelin may be an effective treatment for prostate cancer

Detailed description: 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.

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

Primary outcomes:
measure: Median Time to PSA Progression
timeFrame: Baseline, every 4 weeks during treatment, and up to 12 months after completion of study treatment
Secondary outcomes:
measure: Median PSA Progression-free Survival
timeFrame: Time from randomization to PSA progression or death from any cause
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: University of Chicago Comprehensive Cancer Center
name: Edwin Posadas
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ward JE, Karrison T, Chatta G, Hussain M, Shevrin D, Szmulewitz RZ, O'Donnell PH, Stadler WM, Posadas EM. A randomized, phase II study of pazopanib in castrate-sensitive prostate cancer: a University of Chicago Phase II Consortium/Department of Defense Prostate Cancer Clinical Trials Consortium study. Prostate Cancer Prostatic Dis. 2012 Mar;15(1):87-92. doi: 10.1038/pcan.2011.49. Epub 2011 Oct 18.