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Pazopanib Hydrochloride in Treating Patients With Stage IV or Recurrent Nasopharyngeal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00454142
First received: March 27, 2007
Last updated: November 16, 2015
Last verified: January 2012
  Purpose
This phase II trial studies the side effects and how well pazopanib hydrochloride works in treating patients with stage IV or recurrent nasopharyngeal 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.

Condition Intervention Phase
Recurrent Lymphoepithelioma of the Nasopharynx
Recurrent Squamous Cell Carcinoma of the Nasopharynx
Stage IV Lymphoepithelioma of the Nasopharynx
Stage IV Squamous Cell Carcinoma of the Nasopharynx
Drug: pazopanib hydrochloride
Other: pharmacological study
Procedure: computed tomography
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of GW786034 (Pazopanib) in Asian Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Clinical Benefit Rate [ Time Frame: 12 weeks of treatment ] [ Designated as safety issue: No ]
    Clinical benefit rate (CBR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST ver 1.0) and assessed by CT or MRI. CBR includes 1) Complete response (CR): disappearance of all lesions; 2) partial response (PR): >=30% decrease in the sum of the longest diameter of target lesions and 3) stable disease (SD): non-PR and non progressive disease.


Secondary Outcome Measures:
  • Response Rate (PR) [ Time Frame: 12 weeks of treatment ] [ Designated as safety issue: No ]
    Per response evaluation criteria in solid tumors (RECIST v1.0) and assessed by MRI or CT: Partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions and non-PD (PD: progressive disease) of non-target lesions.

  • Progression-free Survival [ Time Frame: From the date of enrollment to the date of first documented progression or death, whichever occurs first, or to the date when the patient was last known to be alive, up to 3 years. ] [ Designated as safety issue: No ]
    Progression will be evaluated in this study using the new international criteria proposed by RECIST Committee. The sample proportion and associated 95% confidence interval will be reported.

  • Overall Survival [ Time Frame: From date of enrollment to the study to the date of death from any cause or to the date when the patient was last known to be alive, up to 3 years. ] [ Designated as safety issue: No ]
  • Toxicity Profile: Percentage of Participants With Significant (Grade 3/4) Related Adverse Event (AE) [ Time Frame: From the time of first treatment with pazopanib hydrochloride to up to 30days after completion of treatment ] [ Designated as safety issue: Yes ]
    The frequencies of grade 3/4 related toxicities were recorded among all participants, and the percentage of participants who experienced significant AEs were reported.

  • Pharmacodynamic Study: Tumor Blood Flow at Baseline [ Time Frame: Pretreatment ] [ Designated as safety issue: No ]
    Dynamic-contrast enhanced computed tomography (DCE-CT) was performed at baseline and Day 28, tumor blood flow was measured.19 of 33 patients had evaluable DCE-CT data.

  • Pharmacodynamic Study: Tumor Blood Flow on Day 28 [ Time Frame: 28 days post treatment ] [ Designated as safety issue: No ]
    DCE-CT was performed on Day 28 and tumor blood flow was measured. 19 of 33 patients had evaluable DCE-CT data.

  • Pharmacokinetic Study: Percentage of Participants With Trough Concentration at Steady State (Day 28) Above 15 µg/mL [ Time Frame: Day 28 of treatment ] [ Designated as safety issue: No ]
    Pazopanib pharmacokinetic parameters were estimated on Day 1 and Day 28 (steady state). Trough concentration of pazopanib was measured on Day 28 with blood sampling at zero (pre dose), 0.5 hr, 1, 2, 3, 4, 5, 6, 8 and 24 hrs after Day 28 dose.

  • Pharmacokinetic Study: AUC0-24h/Dose on Day 1 [ Time Frame: Day 1 of treatment ] [ Designated as safety issue: No ]
    AUC 0-24h/dose were measured on day 1 for 26 evaluable participants. Blood sampling is done at zero (pre-dose), 0.5 hr, 1, 2, 3, 4, 5, 6 and 8 hrs after the first dose.

  • Pharmacokinetic Study: Area Under Curve (AUC) 0-24h/Dose on Day 28 [ Time Frame: Day 28 of treatment ] [ Designated as safety issue: No ]
    AUC 0-24h/dose were measured on day 28 for 26 evaluable participants. Blood sampling was done at zero (pre dose), 0.5 hr, 1, 2, 3, 4, 5, 6, 8 and 24 hrs after day 28 dose.

  • Pharmacokinetic Study: Volume of Distribution (Vd/F/Dose) on Day 1 [ Time Frame: Day 1 of treatment ] [ Designated as safety issue: No ]
    Volume of distribution (Vd/F/dose) were measured on day 1 for 26 evaluable participants. Blood sampling was done at zero (pre dose), 0.5 hr, 1, 2, 3, 4, 5, 6, 8 hrs after first dose.

  • Pharmacokinetic Study: Volume of Distribution at Steady State (Vss/F/Dose) on Day 28 [ Time Frame: Day 28 of treatment ] [ Designated as safety issue: No ]
    Volume of distribution at steady state (Vss/F/Dose) were measured on day 28 for 26 evaluable participants. Blood sampling was done at zero (pre dose), 0.5 hr, 1, 2, 3, 4, 5, 6, 8 and 24 hrs after day 28 dose.


Enrollment: 33
Study Start Date: August 2007
Study Completion Date: August 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (pazopanib hydrochloride)

Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Pharmacological study will be done on Day 1 and Day 28. Computed tomography will be done at baseline and day 28.

Drug: pazopanib hydrochloride
Given PO
Other Names:
  • GW786034B
  • Votrient
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Procedure: computed tomography
Correlative studies
Other Name: tomography, computed

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the efficacy of pazopanib hydrochloride in patients with stage IV or recurrent nasopharyngeal carcinoma.

II. Determine the progression-free survival of patients treated with this drug. III. Determine the toxicity of this drug in these patients. IV. Determine the effect of this drug on angiogenesis inhibition using dynamic contrast-enhanced computed tomography (CT) scan.

V. Determine the pharmacokinetic profile of this drug in these patients. VI. Correlate the effect of this drug on angiogenesis inhibition with the clinical benefit rate and pharmacokinetics.

OUTLINE:

Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed nasopharyngeal carcinoma, meeting the following criteria:

    • World Health Organization (WHO) type II-III disease
    • Stage IV or recurrent disease
  • Must have failed at least 1 prior line of chemotherapy for metastatic or recurrent disease
  • Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan
  • No known brain metastases
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 or Karnofsky PS 70-100%
  • Life expectancy > 3 months
  • WBC >= 3,000/mm³
  • Absolute neutrophil count >= 1,500/mm³
  • Platelet count >= 100,000/mm³
  • Bilirubin normal
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times upper limit of normal (ULN)
  • Creatinine normal OR creatinine clearance >= 60 mL/min
  • Proteinuria =< 1+ on 2 consecutive dipsticks taken >= 1 week apart
  • Prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time (PTT) =< 1.2 times ULN
  • Systolic blood pressure (BP) =< 140 mm Hg and diastolic BP =< 90 mm Hg

    • Initiation or adjustment of BP medication allowed provided the average of 3 BP readings are < 140/90 mm Hg prior to study entry
  • No history of allergic reaction attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or to other study agents
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No cerebrovascular accident within the past 6 months
  • No history of any of the following diseases within the past 12 weeks:

    • Myocardial infarction
    • Cardiac arrhythmia
    • Admission for unstable angina
    • Cardiac angioplasty or stenting
    • Venous thrombosis
  • No New York Heart Association (NYHA) class III-IV heart failure

    • Patients with a history of NYHA class II heart failure are eligible provided they are asymptomatic on treatment
  • No significant electrocardiogram (ECG) abnormalities, including QTc prolongation (i.e., QTc >= 500 msec)
  • No serious or non-healing wound, ulcer, or bone fracture
  • No condition that would impair the ability to swallow and retain pazopanib hydrochloride, including any of the following:

    • Gastrointestinal tract disease resulting in an inability to take oral medication
    • Requirement for IV alimentation
    • Prior surgical procedures affecting absorption
    • Active peptic ulcer disease
  • No concurrent uncontrolled illness including, but not limited to, the following:

    • Coagulopathy
    • Ongoing or active infection
    • Psychiatric illness or social situation that would preclude study compliance
  • No known allergy to CT contrast agents
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
  • More than 4 weeks since prior radiotherapy
  • At least 4 weeks since prior surgery
  • No prior antiangiogenesis therapy
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy
  • No concurrent medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of pazopanib hydrochloride, as determined by the Principal Investigator
  • No concurrent medications that have the potential to interact with the cytochrome P450 (CYP) isoenzymes CYP2C9 and CYP3A4
  • No concurrent therapeutic warfarin

    • Low molecular weight heparin or prophylactic low-dose warfarin allowed
  • No concurrent antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients
  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: NCT00454142

Locations
Singapore
Cancer Therapeutics Research Group
Singapore, Singapore, 119074
National University Hospital
Singapore, Singapore, 119074
National Cancer Centre
Singapore, Singapore, 169610
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Wan Teck Lim National Cancer Centre
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00454142     History of Changes
Other Study ID Numbers: NCI-2009-00197  NCI-2009-00197  CDR0000537520  CTRG-NP05/25/06  NCC-06-01  7623 
Study First Received: March 27, 2007
Results First Received: December 12, 2014
Last Updated: November 16, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases

ClinicalTrials.gov processed this record on December 02, 2016