The purpose of this study is to determine the 4-month Progression-Free Survival (PFS), with demonstrated increase in tumor doubling time, of eligible subjects treated with pazopanib according to RECIST version 1.1 guidelines.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
For subjects \> 18 years of age and subjects 16-17 years of age with a BSA ≥ 1.6 Pazopanib 800mg once daily will be started on Cycle 1 Day 1 and will be administered continuously for each 28-day cycle. Subjects may continue study treatment until they develop disease progression or unacceptable toxicity. For subjects 16-17 years of age with a BSA \< 1.6 m2, Pazopanib 600mg once daily will be started on Cycle 1 Day 1 and will be administered continuously for each 28-day cycle. Subjects may continue study treatment until they develop disease progression or unacceptable toxicity.
City of Hope
Duarte, California, United States
Massachusetts General Hospital/Dana Farber Cancer Institute
Boston, Massachusetts, United States
Mayo Clinic
Rochester, Minnesota, United States
MD Anderson Cancer Center
Houston, Texas, United States
4-month Progression Free Survival (PFS) per RECIST version 1.1 guidelines
The primary objective of the study is to evaluate the 4-month PFS (with demonstrated increase in tumor doubling time) of eligible subjects treated with pazopanib according to RECIST version 1.1 guidelines. Tumor growth rate will be calculated by measuring growth at the specified intervals for the single, longest dimension of the tumor(s) (RECIST) and by calculating the area of the tumor(s), which will be the product of the longest dimension of the tumor(s) multiplied by its longest, perpendicular dimension (WHO). Progressive disease (PD) for target lesions is defined as at least a 20% increase in the sum of diameters of the target lesions taking as reference the smallest sum on study, and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. PD for non-target lesions is defined as unequivocal appearance of one or more new malignant lesions. Unequivocal progression of existing non-target lesions.
Time frame: 4 months from the beginning of study treatment
4-month PFS per WHO criteria
The primary objective of the study is to evaluate the 4-month PFS (with demonstrated increase in tumor doubling time) of eligible subjects treated with pazopanib according to RECIST version 1.1 guidelines. The study statistician will calculate tumor growth rate per WHO criteria based on bidimensional tumor measurements (i.e., longest dimension of the tumor(s) and its longest perpendicular dimension) at each imaging time point.
Time frame: 4 months from the beginning of study treatment
Pharmacokinetics evaluation
Evaluate the pharmacokinetics of pazopanib to define correlation of minimal drug concentrations with PFS, RR, duration of response, OS, and safety. Samples will be collected on Day 1 of Cycles 2 and 3 for plasma pazopanib trough PKs to assess the population of subjects with concentration greater than the target of 15 µg/mL.
Time frame: Day 1 of Cycles 2 and 3 (Approximately 5 and 7 weeks from the start of study treatment)
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Tumor growth kinetics
Evaluate the tumor growth kinetics, both within subject, and across subjects over time and the change associated with pazopanib. Examine the correlation between tumor growth kinetics with pazopanib pharmacokinetics.
Time frame: Assessed at Week -4 and 3 to 5 days prior to study treatment, approximately 4 weeks from the start of study treatment and every 6 weeks thereafter until the patient progresses or 60 months from the end of treatment, whichever occurs first
Response rate per RECIST version 1.1
Response rate (RR), where response is defined as complete response (CR) or partial response (PR) according to RECIST version 1.1 guidelines.
Time frame: Assessed at Week -4 and 3 to 5 days prior to study treatment, approximately 4 weeks from the start of study treatment and every 6 weeks thereafter until the patient progresses or 60 months from the end of treatment, whichever occurs first
Overall Survival (OS)
The time origin for OS will be Cycle 1, Day 1. Subjects will be followed for up to 24 months after the end of treatment or until death, lost to follow-up, or withdrawal of consent, whichever occurs first.
Time frame: Cycle 1 Day 1 (start of study treatment) up to death or 60 months after the end of study treatment, whichever occurs first
PFS
The time origin for PFS will be Cycle 1, Day 1. Repeat radiological imaging will be conducted after every 2 cycles of treatment (approximately 8 weeks)to evaluate disease status per RECIST v.1.1 and WHO criteria. Subjects who discontinue study treatment for reasons other than disease progression will continue to have their disease status reported every 3 months post end of treatment up to 60 months.
Time frame: Assessed at Week -4 and 3 to 5 days prior to study treatment, approximately 4 weeks from the start of study treatment and every 6 weeks thereafter until the patient progresses or 60 months from the end of treatment, whichever occurs first
Response rate per WHO criteria
Response rate (RR), where response is defined as complete response (CR) or partial response (PR) per WHO criteria.
Time frame: Assessed at Week -4 and 3 to 5 days prior to study treatment, approximately 4 weeks from the start of study treatment and every 6 weeks thereafter until the patient progresses or 60 months from the end of treatment, whichever occurs first