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

Stage IV Squamous Cell Carcinoma of the Nasopharynx Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00454142
• Other study ID #: NCI-2009-00197
• Secondary ID: NCI-2009-00197CD
• Status: Completed
• Phase: Phase 2
• First received: March 27, 2007
• Last updated: November 16, 2015
• Start date: August 2007
• Est. completion date: August 2010

Study information

• Verified date: January 2012
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: August 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Nasopharyngeal Neoplasms
• 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

Drug:
• pazopanib hydrochloride
Given PO

Other:
• pharmacological study
Correlative studies

Procedure:
• computed tomography
Correlative studies

Locations

Country	Name	City	State
Singapore	Cancer Therapeutics Research Group	Singapore
Singapore	National Cancer Centre	Singapore
Singapore	National University Hospital	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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.	No
Secondary	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.	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No