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

A Phase 2 Study of GW786034 (Pazopanib) in Asian Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma

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.

Study Overview

• Status: Completed
• 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
• Intervention / Treatment: Drug: pazopanib hydrochloride; Other: pharmacological study; Procedure: computed tomography

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
  • Singapore, Singapore, 169610
    • National Cancer Centre
  • Singapore, Singapore, 119074
    • Cancer Therapeutics Research Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: pharmacological studies; Procedure: computed tomography; Correlative studies; Other Names: tomography, computed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Rate	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.	12 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate (PR)	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.	12 weeks of treatment
Progression-free Survival	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.	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.
Overall Survival		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.
Toxicity Profile: Percentage of Participants With Significant (Grade 3/4) Related Adverse Event (AE)	The frequencies of grade 3/4 related toxicities were recorded among all participants, and the percentage of participants who experienced significant AEs were reported.	From the time of first treatment with pazopanib hydrochloride to up to 30days after completion of treatment
Pharmacodynamic Study: Tumor Blood Flow at Baseline	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.	Pretreatment
Pharmacodynamic Study: Tumor Blood Flow on Day 28	DCE-CT was performed on Day 28 and tumor blood flow was measured. 19 of 33 patients had evaluable DCE-CT data.	28 days post treatment
Pharmacokinetic Study: Percentage of Participants With Trough Concentration at Steady State (Day 28) Above 15 µg/mL	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.	Day 28 of treatment
Pharmacokinetic Study: AUC0-24h/Dose on Day 1	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.	Day 1 of treatment
Pharmacokinetic Study: Area Under Curve (AUC) 0-24h/Dose on Day 28	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.	Day 28 of treatment
Pharmacokinetic Study: Volume of Distribution (Vd/F/Dose) on Day 1	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.	Day 1 of treatment
Pharmacokinetic Study: Volume of Distribution at Steady State (Vss/F/Dose) on Day 28	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.	Day 28 of treatment

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Wan Teck Lim, National Cancer Centre

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: March 27, 2007
• First Submitted That Met QC Criteria: March 27, 2007
• First Posted (Estimate): March 30, 2007

Study Record Updates

• Last Update Posted (Estimate): December 17, 2015
• Last Update Submitted That Met QC Criteria: November 16, 2015
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Neoplasms, Squamous Cell; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Recurrence; Carcinoma, Squamous Cell
• Other Study ID Numbers: NCI-2009-00197 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000537520 (Registry Identifier: NCI); CTRG-NP05/25/06 (Other Identifier: Cancer Therapeutics Research Group (CTRG)); NCC-06-01 (Other Identifier: National Cancer Centre); 7623 (Other Identifier: CTEP)