Pazopanib Hydrochloride After Leuprolide Acetate or Goserelin Acetate in Treating Patients With Relapsed Prostate Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00454571
First received: March 27, 2007
Last updated: January 14, 2013
Last verified: September 2012
  Purpose

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


Condition Intervention Phase
Recurrent Prostate Cancer
Drug: pazopanib hydrochloride
Other: active surveillance
Drug: leuprolide acetate
Drug: goserelin acetate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Phase II Study of GW786034 (Pazopanib) in Stage D0 Relapsed Androgen Sensitive Prostate Cancer Following Limited GnRH Agonist Therapy

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Time to PSA progression [ Time Frame: Baseline, every 4 weeks during treatment, and up to 12 months after completion of study treatment ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • PSA progression-free survival [ Time Frame: Time from randomization to PSA progression or death from any cause ] [ Designated as safety issue: No ]
    Kaplan-Meier curves will be generated and the pazopanib and active surveillance groups compared using the log rank test.

  • Adverse events [ Time Frame: At baseline, day 1 of course 1, every 4 weeks during treatment, and up to 12 months after completion of study treatment ] [ Designated as safety issue: Yes ]
    Adverse events data will be compared between the pazopanib-treated and control groups. Patients will be classified by type of toxicity and worst severity grade. The frequency of toxicity in the pazopanib and observation groups will be compared using chi square or Fisher's exact test, as appropriate.


Estimated Enrollment: 98
Study Start Date: June 2006
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (enzyme inhibitor therapy)
Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: pazopanib hydrochloride
Given PO
Other Names:
  • GW786034B
  • Votrient
Other: active surveillance
Undergo clinical observation
Drug: leuprolide acetate
Other Names:
  • Enantone
  • LEUP
  • Lupron
  • Lupron Depot
Drug: goserelin acetate
Other Names:
  • ICI-118630
  • ZDX
  • Zoladex
Arm II (No intervention)
Patients undergo observation.
Other: active surveillance
Undergo clinical observation
Drug: leuprolide acetate
Other Names:
  • Enantone
  • LEUP
  • Lupron
  • Lupron Depot
Drug: goserelin acetate
Other Names:
  • ICI-118630
  • ZDX
  • Zoladex

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00454571

Locations
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Investigators
Principal Investigator: Edwin Posadas University of Chicago Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00454571     History of Changes
Other Study ID Numbers: NCI-2009-00202, N01CM62201, CDR0000538086, 14954A
Study First Received: March 27, 2007
Last Updated: January 14, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Leuprolide
Goserelin
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 29, 2014