Pazopanib Hydrochloride in Treating Patients With Advanced or Refractory Solid Tumors
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|ClinicalTrials.gov Identifier: NCT01552356|
Recruitment Status : Active, not recruiting
First Posted : March 13, 2012
Last Update Posted : December 10, 2018
|Condition or disease||Intervention/treatment||Phase|
|Solid Neoplasm||Other: Laboratory Biomarker Analysis Drug: Pazopanib Hydrochloride Other: Pharmacological Study||Phase 1|
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.
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 (Clinical Trial)|
|Actual Enrollment :||54 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pharmacokinetic-Driven Individualization of Pazopanib Therapy in Patients With Solid Tumors: A Phase I Study|
|Actual Study Start Date :||March 19, 2012|
|Actual Primary Completion Date :||December 31, 2015|
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. Course length can be extended to 56 days at the discretion of the treating physician after 12 courses (1 year) of treatment on study.
Other: Laboratory Biomarker Analysis
Drug: Pazopanib Hydrochloride
Other: Pharmacological 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 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 [ Time Frame: Up to 3 months ]The number and severity of all adverse events (overall, by dose-level and diet, and by tumor group) will be tabulated and summarized.
- Incidence of grade 3+ adverse events, as assessed by the NCI CTCAE version 4.0 [ Time Frame: Up to 3 months ]The number and severity of grade 3+ adverse events will be tabulated and summarized.
- Toxicity profile, as assessed by the NCI CTCAE version 4.0 [ Time Frame: Up to 3 months ]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.
- Response profile, assessed using modified Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 3 months ]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 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 [ Time Frame: At baseline, at 24 hours after pazopanib hydrochloride and day 14 of course 1, and at 14 days of dosage change ]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.
- Steady state pazopanib hydrochloride trough levels [ Time Frame: 24 hours after initiation of 800 mg daily fasting ]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.
- Trough pazopanib hydrochloride levels [ Time Frame: After 14 days of pazopanib hydrochloride administration ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01552356
|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|