Trial Outcomes & Findings for Pazopanib Hydrochloride in Treating Patients With Stage IV or Recurrent Nasopharyngeal Cancer (NCT NCT00454142)

NCT ID: NCT00454142

Last Updated: 2015-12-17

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 33 participants
• Primary outcome timeframe: 12 weeks of treatment
• Results posted on: 2015-12-17

Participant Flow

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.

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.

Participant milestones

Measure	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
Overall Study STARTED	33
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	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
Overall Study Withdrawal by Subject	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Treatment (Tyrosine Kinase Inhibitor) n=33 Participants 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
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	31 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants
Age, Continuous	50 years STANDARD_DEVIATION 8.4 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants
Region of Enrollment Singapore	33 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks of treatment

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.

Outcome measures

Measure	Treatment (Pazopanib Hydrochloride) n=33 Participants Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. pazopanib hydrochloride: Given PO pharmacological study: Correlative studies computed tomography: Correlative studies
Clinical Benefit Rate	54.5 percentage of participants Interval 38.0 to 70.2

SECONDARY outcome

Timeframe: 12 weeks of treatment

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.

Outcome measures

Measure	Treatment (Pazopanib Hydrochloride) n=33 Participants Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. pazopanib hydrochloride: Given PO pharmacological study: Correlative studies computed tomography: Correlative studies
Response Rate (PR)	6.1 percentage of participants

SECONDARY outcome

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.

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.

Outcome measures

Measure	Treatment (Pazopanib Hydrochloride) n=33 Participants Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. pazopanib hydrochloride: Given PO pharmacological study: Correlative studies computed tomography: Correlative studies
Progression-free Survival	4.4 months Interval 3.9 to 5.8

SECONDARY outcome

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.

Outcome measures

Measure	Treatment (Pazopanib Hydrochloride) n=33 Participants Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. pazopanib hydrochloride: Given PO pharmacological study: Correlative studies computed tomography: Correlative studies
Overall Survival	10.8 months Interval 8.6 to 21.8

SECONDARY outcome

Timeframe: From the time of first treatment with pazopanib hydrochloride to up to 30days after completion of treatment

The frequencies of grade 3/4 related toxicities were recorded among all participants, and the percentage of participants who experienced significant AEs were reported.

Outcome measures

Measure	Treatment (Pazopanib Hydrochloride) n=33 Participants Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. pazopanib hydrochloride: Given PO pharmacological study: Correlative studies computed tomography: Correlative studies
Toxicity Profile: Percentage of Participants With Significant (Grade 3/4) Related Adverse Event (AE)	48 percentage of participants

SECONDARY outcome

Timeframe: Pretreatment

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.

Outcome measures

Measure	Treatment (Pazopanib Hydrochloride) n=19 Participants Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. pazopanib hydrochloride: Given PO pharmacological study: Correlative studies computed tomography: Correlative studies
Pharmacodynamic Study: Tumor Blood Flow at Baseline	52.2 ml/100ml/min Standard Deviation 13.6

SECONDARY outcome

Timeframe: 28 days post treatment

DCE-CT was performed on Day 28 and tumor blood flow was measured. 19 of 33 patients had evaluable DCE-CT data.

Outcome measures

Measure	Treatment (Pazopanib Hydrochloride) n=19 Participants Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. pazopanib hydrochloride: Given PO pharmacological study: Correlative studies computed tomography: Correlative studies
Pharmacodynamic Study: Tumor Blood Flow on Day 28	35.7 ml/100ml/min Standard Deviation 18.5

SECONDARY outcome

Timeframe: Day 28 of treatment

Population: 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.

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.

Outcome measures

Measure	Treatment (Pazopanib Hydrochloride) n=26 Participants Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. pazopanib hydrochloride: Given PO pharmacological study: Correlative studies computed tomography: Correlative studies
Pharmacokinetic Study: Percentage of Participants With Trough Concentration at Steady State (Day 28) Above 15 µg/mL	92 percentage of participants

SECONDARY outcome

Timeframe: Day 1 of treatment

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.

Outcome measures

Measure	Treatment (Pazopanib Hydrochloride) n=26 Participants Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. pazopanib hydrochloride: Given PO pharmacological study: Correlative studies computed tomography: Correlative studies
Pharmacokinetic Study: AUC0-24h/Dose on Day 1	836.23 hr*ng/mL/mg Interval 165.73 to 1869.21

SECONDARY outcome

Timeframe: Day 28 of treatment

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.

Outcome measures

Measure	Treatment (Pazopanib Hydrochloride) n=26 Participants Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. pazopanib hydrochloride: Given PO pharmacological study: Correlative studies computed tomography: Correlative studies
Pharmacokinetic Study: Area Under Curve (AUC) 0-24h/Dose on Day 28	1192.35 hr*ng/mL/mg Interval 82.96 to 4345.95

SECONDARY outcome

Timeframe: Day 1 of treatment

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.

Outcome measures

Measure	Treatment (Pazopanib Hydrochloride) n=26 Participants Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. pazopanib hydrochloride: Given PO pharmacological study: Correlative studies computed tomography: Correlative studies
Pharmacokinetic Study: Volume of Distribution (Vd/F/Dose) on Day 1	18.09 mL/mg Interval 8.34 to 79.02

SECONDARY outcome

Timeframe: Day 28 of treatment

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.

Outcome measures

Measure	Treatment (Pazopanib Hydrochloride) n=26 Participants Patients receive pazopanib hydrochloride PO QD on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. pazopanib hydrochloride: Given PO pharmacological study: Correlative studies computed tomography: Correlative studies
Pharmacokinetic Study: Volume of Distribution at Steady State (Vss/F/Dose) on Day 28	80.23 mL/mg Interval 16.58 to 1601.7

Adverse Events

Treatment (Tyrosine Kinase Inhibitor)

Serious events: 10 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treatment (Tyrosine Kinase Inhibitor) n=33 participants at risk 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
Respiratory, thoracic and mediastinal disorders infection	6.1% 2/33 • Number of events 2 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
Cardiac disorders Pericardial effusion	3.0% 1/33 • Number of events 1 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
Blood and lymphatic system disorders Hemorrhage	9.1% 3/33 • Number of events 3 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
Hepatobiliary disorders Hyperbilirubin	3.0% 1/33 • Number of events 1 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
Nervous system disorders Pain	3.0% 1/33 • Number of events 1 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
Musculoskeletal and connective tissue disorders Pain	3.0% 1/33 • Number of events 1 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
Cardiac disorders Myocardial infarction	3.0% 1/33 • Number of events 1 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.

Other adverse events

Measure	Treatment (Tyrosine Kinase Inhibitor) n=33 participants at risk 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
Gastrointestinal disorders Anorexia	9.1% 3/33 • Number of events 3 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
General disorders Dehydration	3.0% 1/33 • Number of events 1 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
Gastrointestinal disorders Diarrhea	6.1% 2/33 • Number of events 2 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
General disorders Fatigue	15.2% 5/33 • Number of events 5 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
Skin and subcutaneous tissue disorders Hand-foot-skin reaction	15.2% 5/33 • Number of events 5 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
Cardiac disorders Hypertension	3.0% 1/33 • Number of events 1 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
Metabolism and nutrition disorders hyponatremia	3.0% 1/33 • Number of events 1 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
General disorders Lethargy	3.0% 1/33 • Number of events 1 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
Blood and lymphatic system disorders Neutropenic fever	3.0% 1/33 • Number of events 1 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
Metabolism and nutrition disorders Proteinuria	3.0% 1/33 • Number of events 1 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.
Gastrointestinal disorders Vomiting	6.1% 2/33 • Number of events 2 • From the time of first treatment with pazopanib hydrochloride to up to 1 month after completion of treatment.

Additional Information

Dr. Wan Teck LIM

National Cancer Centre Singapore

Phone: 65-64368174

Email: dmolwt@nccs.com.sg

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60