Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 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 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (pazopanib hydrochloride) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| pazopanib hydrochloride | Drug | Given PO |
|
| 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 |
| 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 |
Not provided
Inclusion Criteria:
Histologically or cytologically confirmed nasopharyngeal carcinoma, meeting the following criteria:
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
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:
No New York Heart Association (NYHA) class III-IV heart failure
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:
No concurrent uncontrolled illness including, but not limited to, the following:
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
No concurrent antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Wan Teck Lim | National Cancer Centre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cancer Therapeutics Research Group | Singapore | 119074 | Singapore | |||
| National University Hospital |
Once a subject signed the informed consent form, the required screening procedures would be performed.Eligible subjects would undergo 2 times of DCE-CT scan before study drug administration.
Subjects were screened and enrolled from 2 sites in Singapore, 27 were enrolled from National Cancer Centre Singapore and 6 were enrolled from National University Hospital.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Treatment (Tyrosine Kinase Inhibitor) | Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. computed tomography : Correlative studies pharmacological study : Correlative studies pazopanib hydrochloride : Given PO |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| pharmacological study | Other | Correlative studies |
|
|
| computed tomography | Procedure | Correlative studies |
|
|
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 |
| Singapore |
| 119074 |
| Singapore |
| National Cancer Centre | Singapore | 169610 | Singapore |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Tyrosine Kinase Inhibitor) | Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. computed tomography : Correlative studies pharmacological study : Correlative studies pazopanib hydrochloride : Given PO |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Number | percentage of participants | 12 weeks of treatment |
|
|
| |||||||||||||||||||||||||||
| 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. | Posted | Median | 95% Confidence Interval | months | 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. |
|
| |||||||||||||||||||||||||||
| 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. | Posted | Number | 95% Confidence Interval | percentage of participants | 12 weeks of treatment |
|
| |||||||||||||||||||||||||||
| Secondary | Overall Survival | Posted | Median | 95% Confidence Interval | months | 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. |
|
| ||||||||||||||||||||||||||||
| 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. | Posted | Number | percentage of participants | From the time of first treatment with pazopanib hydrochloride to up to 30days after completion of treatment |
|
| ||||||||||||||||||||||||||||
| 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. | Posted | Mean | Standard Deviation | ml/100ml/min | Pretreatment |
|
| |||||||||||||||||||||||||||
| 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. | Posted | Mean | Standard Deviation | ml/100ml/min | 28 days post treatment |
|
| |||||||||||||||||||||||||||
| 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. | Patients (total 26) with both Day 1 and Day 28 pharmacokinetic parameters were included.The trough concentration of pazopanib on Day 28 was observed to be above 15ug/ml in approximately 92% of patients at steady state. | Posted | Number | percentage of participants | Day 28 of treatment |
|
| |||||||||||||||||||||||||||
| 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. | Posted | Median | Full Range | hr*ng/mL/mg | Day 1 of treatment |
|
| |||||||||||||||||||||||||||
| 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. | Posted | Median | Full Range | hr*ng/mL/mg | Day 28 of treatment |
|
| |||||||||||||||||||||||||||
| 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. | Posted | Median | Full Range | mL/mg | Day 1 of treatment |
|
| |||||||||||||||||||||||||||
| 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. | Posted | Median | Full Range | mL/mg | Day 28 of treatment |
|
|
From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment (Tyrosine Kinase Inhibitor) | Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. computed tomography : Correlative studies pharmacological study : Correlative studies pazopanib hydrochloride : Given PO | 10 | 33 | 11 | 33 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| infection | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Pericardial effusion | Cardiac disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Hemorrhage | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Hyperbilirubin | Hepatobiliary disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Pain | Nervous system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Pain | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anorexia | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Dehydration | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Hand-foot-skin reaction | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Hypertension | Cardiac disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| hyponatremia | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Lethargy | General disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Neutropenic fever | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Proteinuria | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Wan Teck LIM | National Cancer Centre Singapore | 65-64368174 | dmolwt@nccs.com.sg |
| ID | Term |
|---|---|
| C516667 | pazopanib |
Not provided
Not provided
Not provided
|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
|
|
|
|
|
|
|
|