This phase I trial studies the side effects and the best dose of pazopanib hydrochloride in treating patients with solid tumors that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or does not respond to treatment (refractory). Pazopanib hydrochloride may prevent the growth of new blood vessels that tumors need to grow. Studying samples of blood in the laboratory from patients receiving pazopanib hydrochloride may help doctors learn more about the effects of the body on the drug. It may also help doctors understand how well patients respond to treatment.
PRIMARY OBJECTIVES: I. To assess the feasibility and safety of individualizing pazopanib (pazopanib hydrochloride) monotherapy based upon attained pazopanib plasma concentrations so as to achieve desired target pazopanib plasma concentration in the highest possible fraction of treated patients. SECONDARY OBJECTIVES: I. To assess whether patient cytochrome P450 (CYP) or other polymorphisms may correlate with attained pazopanib levels in response to standard pazopanib dosing. II. To assess whether patient trough pazopanib levels attained 24 hours after initiation of 800 mg daily fasting may predict steady state trough pazopanib levels after 14 days of pazopanib administration. III. To assess whether patient trough pazopanib levels may correlate with observed pazopanib toxicities. OUTLINE: This is a dose-escalation study. Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Course length can be extended to 56 days at the discretion of the treating physician after 12 courses (1 year) of treatment on study. After completion of study treatment, patients are followed up for 3 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Correlative studies
Given PO
Correlative studies
Mayo Clinic in Florida
Jacksonville, Florida, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Biologically optimal dose (BOD) defined as the dose level and diet in combination that induces no toxicity requiring dose modification per protocol and achieves a satisfactory pazopanib trough concentration (Cmin greater than 30 ug/mL)
Time frame: At 14 days
Adverse events profile, as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
The number and severity of all adverse events (overall, by dose-level and diet, and by tumor group) will be tabulated and summarized.
Time frame: Up to 3 months
Incidence of grade 3+ adverse events, as assessed by the NCI CTCAE version 4.0
The number and severity of grade 3+ adverse events will be tabulated and summarized.
Time frame: Up to 3 months
Toxicity profile, as assessed by the NCI CTCAE version 4.0
Non-hematologic toxicities will be evaluated via the ordinal CTC standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
Time frame: Up to 3 months
Response profile, assessed using modified Response Evaluation Criteria in Solid Tumors (RECIST)
Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population The summary will be overall and by tumor group, and particularly by cohorts (first 34 patients vs. expansion cohort where a possibly refined definition of disease progression will be used).
Time frame: Up to 3 months
Time until any treatment-related toxicity, as assessed by the NCI CTCAE version 4.0
Time frame: Up to 3 months
Time until treatment-related grade 3+ toxicity, as assessed by the NCI CTCAE version 4.0
Time frame: Up to 3 months
Time until hematologic nadirs (ANC, platelets, hemoglobin) , as assessed by the NCI CTCAE version 4.0
Time frame: Up to 3 months
Time to progression according to RECIST version 1.1
Time frame: Up to 3 months
Time to treatment failure
Time frame: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months
Pazopanib hydrochloride levels attained in response to standard dosing
Descriptive statistics, simple scatter plots and linear regression model will form the basis of presentation of these data. Attained levels will be correlated with cytochrome P450 and other polymorphisms and with observed toxicities.
Time frame: At baseline, at 24 hours after pazopanib hydrochloride and day 14 of course 1, and at 14 days of dosage change
Steady state pazopanib hydrochloride trough levels
Descriptive statistics, simple scatter plots and linear regression model will form the basis of presentation of these data. Will be correlated with steady state trough levels after 14 days.
Time frame: 24 hours after initiation of 800 mg daily fasting
Trough pazopanib hydrochloride levels
Descriptive statistics, simple scatter plots and linear regression model will form the basis of presentation of these data. Trough levels will be correlated with observed toxicities.
Time frame: After 14 days of pazopanib hydrochloride administration
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