Pazopanib Hydrochloride in Treating Patients With Advanced or Refractory Solid Tumors
This phase I trial studies the side effects and the best dose of pazopanib hydrochloride in treating patients with advanced or refractory solid tumors. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Unspecified Adult Solid Tumor, Protocol Specific
Drug: pazopanib hydrochloride
Other: pharmacological study
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pharmacokinetic-Driven Individualization of Pazopanib Therapy in Patients With Solid Tumors: a Phase I Study|
- 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 > 30 μg/mL) [ Time Frame: At 14 days ] [ Designated as safety issue: No ]
- Time until any treatment-related toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]The number and severity of all adverse events (overall, by dose-level and diet, and by tumor group) will be tabulated and summarized in this patient population.
- Time to progression according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: Up to 3 months ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Correlation between CYP and other polymorphisms with attained pazopanib levels in response to standard pazopanib dosing [ Time Frame: At baseline, at 24 hours after pazopanib and day 14 of course 1, and at 14 days of dosage change ] [ Designated as safety issue: No ]Descriptive statistics, simple scatter plots and linear regression model will form the basis of presentation of these data.
- Correlation between pazopanib levels with observed pazopanib toxicities [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2012|
|Estimated Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (pazopanib hydrochloride)
Patients receive pazopanib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: pazopanib hydrochloride
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
I. To assess the feasibility and safety of individualizing pazopanib hydrochloride (pazopanib) monotherapy based upon attained pazopanib plasma concentrations so as to achieve desired target pazopanib plasma concentration in the highest possible fraction of treated patients.
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.
Patients undergo blood sample collection at baseline and periodically during treatment for biomarker analysis, pharmacokinetic, and pharmacogenomic studies.
After completion of study treatment, patients are followed up for 3 months.
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224-9980|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Keith Bible||Mayo Clinic|