Clinical trial NCT00454142: Pazopanib Hydrochloride in Treating Patients With Stage IV or Recurrent Nasopharyngeal Cancer
Official title: A Phase 2 Study of GW786034 (Pazopanib) in Asian Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-03-30
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Clinical Benefit Rate
timeFrame: 12 weeks of treatment
Secondary outcomes:
measure: Response Rate (PR)
timeFrame: 12 weeks of treatment
measure: Progression-free Survival
timeFrame: 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.
measure: Overall Survival
timeFrame: 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.
measure: Toxicity Profile: Percentage of Participants With Significant (Grade 3/4) Related Adverse Event (AE)
timeFrame: From the time of first treatment with pazopanib hydrochloride to up to 30days after completion of treatment
measure: Pharmacodynamic Study: Tumor Blood Flow at Baseline
timeFrame: Pretreatment
measure: Pharmacodynamic Study: Tumor Blood Flow on Day 28
timeFrame: 28 days post treatment
measure: Pharmacokinetic Study: Percentage of Participants With Trough Concentration at Steady State (Day 28) Above 15 µg/mL
timeFrame: Day 28 of treatment
measure: Pharmacokinetic Study: AUC0-24h/Dose on Day 1
timeFrame: Day 1 of treatment
measure: Pharmacokinetic Study: Area Under Curve (AUC) 0-24h/Dose on Day 28
timeFrame: Day 28 of treatment
measure: Pharmacokinetic Study: Volume of Distribution (Vd/F/Dose) on Day 1
timeFrame: Day 1 of treatment
measure: Pharmacokinetic Study: Volume of Distribution at Steady State (Vss/F/Dose) on Day 28
timeFrame: Day 28 of treatment
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Cancer Therapeutics Research Group
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre
Study officials:
affiliation: National Cancer Centre
name: Wan Teck Lim
role: PRINCIPAL_INVESTIGATOR
References: