Recruitment

Recruitment Status
Active, not recruiting
Estimated Enrollment
30

Inclusion Criteria

< Grade 2 hypo/hyperkalemia
Absolute neutrophil count (ANC) >= 1,500/uL
< Grade 3 hypo/hypercalcemia
...
< Grade 2 hypo/hyperkalemia
Absolute neutrophil count (ANC) >= 1,500/uL
< Grade 3 hypo/hypercalcemia
Measurable disease
Creatinine =< 1.5 times ULN OR measured creatinine clearance of >= 60 mL/min 1.73 m^2
Willing to return to Mayo Clinic for follow up
Direct bilirubin =< 1.5 X upper limit of normal (ULN) (subjects with Gilbert's syndrome and elevations of indirect bilirubin only are eligible)
Urine protein/creatinine ratio < 1 or 24-hour urine < 1 gram
< Grade 3 hypo/hypermagnesemia
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
International normalized ratio (INR) < 1.2 times ULN; (Note: use of warfarin is prohibited; low molecular weight heparin is allowed, so long as these criteria are met)
< Grade 3 hypo/hyperphosphatemia
Hemoglobin (Hgb) >= 8.0 g/dL
Ability to provide informed consent
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X ULN
Willingness to provide mandatory blood samples for pazopanib drug level assessments required for dosage adjustments, as well as for required pharmacogenomic studies
Activated partial thromboplastin time (APTT) < 1.2 times upper limit of normal (ULN); (Note: use of warfarin is prohibited; low molecular weight heparin is allowed, so long as these criteria are met)
Platelet (PLT) = 100,000/uL
Histologic proof of cancer which is now not amenable to alternative curative or clearly superior standard treatment options
Life expectancy >= 84 days (3 months)
Women of childbearing potential only: negative serum pregnancy test done =< 14 days prior to registration

Exclusion Criteria

Biologic therapy =< 28 days prior to registration
Blood pressure (BP) > 140 mmHg (systolic) and > 90 mmHg (diastolic); initiation or adjustment of BP medication is permitted prior to registration provided that the average of three BP readings at a visit prior to registration is < 140/90 mmHg
Receiving any other investigational agent
...
Biologic therapy =< 28 days prior to registration
Blood pressure (BP) > 140 mmHg (systolic) and > 90 mmHg (diastolic); initiation or adjustment of BP medication is permitted prior to registration provided that the average of three BP readings at a visit prior to registration is < 140/90 mmHg
Receiving any other investigational agent
History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to beginning study treatment
Cardiac angioplasty or stenting
Immunotherapy =< 28 days prior to registration
Corrected QT interval (QTc) >= 480 msec and/or receiving any concomitant medications that are associated with a risk of QTc prolongation and/or torsades de pointes; NOTE: these medications should be discontinued or replaced with drugs that do not carry these risks
Active peptic ulcer disease
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
History of bleeding disorder, including patients afflicted with hemophilia, disseminated intravascular coagulation, or any other abnormality of coagulation potentially predisposing patients to bleeding
Failure to fully recover from acute, reversible effects of prior chemotherapy (other anti-neoplastic therapy) and radiation therapy
Pulmonary embolism, untreated deep venous thrombosis (DVT) or DVT which has been treated with therapeutic anticoagulation for less than 6 weeks
History of hemoptysis in excess of 2.5 mL (1/2 teaspoon ) within 8 weeks prior to first dose of study drug
Radiation therapy =< 28 days prior to registration
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
HIV-positive patients on combination antiretroviral therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
Symptomatic peripheral vascular disease
Other active malignancy =< 3 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history or prior malignancy, they must not be receiving other specific treatment (e.g. hormonal or chemotherapy) for their cancer
Subjects with known brain metastases
Myocardial infarction
Men or women of childbearing potential who are unwilling to employ adequate contraception
Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation
Receiving any medications or substances that are inducers of CYP3A4 (efavirenz, nevirapine, carbamazepine, modafinil, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's wort); use of the aforementioned inducers is prohibited =< 7 days prior to registration
Coronary artery bypass graft surgery
Nursing women
Serious or non-healing wound, ulcer, or bone fracture
Receiving mitotane within 6 months of enrolling on the study
Poorly controlled depression or anxiety disorder, or recent (=< 6 months) suicidal ideation
Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; a subject who has a history of class II heart failure and is asymptomatic on treatment may be considered eligible
Ejection fraction < institutional lower limit of normal (LLN) and/or history of cardiomyopathy
Pregnant women
Receiving a medication with known risk of torsades de pointes; the following medications are specifically prohibited: amiodarone, arsenic trioxide, bepridil, chloroquine, chlorpromazine, cisapride, clarithromycin, disopyramide, dofetilide, dolasetron, droperidol, erythromycin, halofantrine, haloperidol, ibutilide levomethadyl, mesoridazine, methadone, pentamidine, pimozide, procainamide, quinidine, sotalol, sparfloxacin, and thioridazine; patients should be watched carefully for indications of torsades de pointes, such as syncope; performing additional electrocardiograms (EKGs) on subjects who must take one or more of these medications is not required; however, additional investigations, including EKGs, may be performed as per the treating physician's judgment
Mitomycin C/nitrosoureas =< 42 days prior to registration
Prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel
Chemotherapy =< 28 days prior to registration
Current use of therapeutic warfarin; Note: low molecular weight heparin is allowed; prothrombin time (PT)/partial thromboplastin time (PTT) must meet the inclusion criteria
Any lesion, whether induced by tumor, radiation or other conditions, which makes it difficult to swallow capsules or pills
Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 counts < 200
Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
Arterial thrombosis
Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
Known intraluminal metastatic lesions
Receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) (indinavir, nelfinavir, atazanavir, ritonavir, clarithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, saquinavir, telithromycin, aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil, diltiazem); use of the aforementioned strong or moderate inhibitors is prohibited < 7 days prior to registration
Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation); Note: concomitant use of zoledronic acid, pamidronate or denosumab is allowed (and can be initiated while patients are on study therapy at investigator discretion)
Radiation to > 25% of bone marrow
Admission for unstable angina
Prior use of pazopanib (prior use of other kinase inhibitors allowed)
Active peptic ulcer disease
Active cardiac arrhythmia (except sinus arrhythmia, atrial fibrillation, asymptomatic premature ventricular contractions [PVCs])
Malabsorption syndrome

Summary

Conditions
Solid Neoplasm
Type
Interventional
Phase
Phase 1
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

Description

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. SECO...

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.

Inclusion Criteria

< Grade 2 hypo/hyperkalemia
Absolute neutrophil count (ANC) >= 1,500/uL
< Grade 3 hypo/hypercalcemia
...
< Grade 2 hypo/hyperkalemia
Absolute neutrophil count (ANC) >= 1,500/uL
< Grade 3 hypo/hypercalcemia
Measurable disease
Creatinine =< 1.5 times ULN OR measured creatinine clearance of >= 60 mL/min 1.73 m^2
Willing to return to Mayo Clinic for follow up
Direct bilirubin =< 1.5 X upper limit of normal (ULN) (subjects with Gilbert's syndrome and elevations of indirect bilirubin only are eligible)
Urine protein/creatinine ratio < 1 or 24-hour urine < 1 gram
< Grade 3 hypo/hypermagnesemia
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
International normalized ratio (INR) < 1.2 times ULN; (Note: use of warfarin is prohibited; low molecular weight heparin is allowed, so long as these criteria are met)
< Grade 3 hypo/hyperphosphatemia
Hemoglobin (Hgb) >= 8.0 g/dL
Ability to provide informed consent
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X ULN
Willingness to provide mandatory blood samples for pazopanib drug level assessments required for dosage adjustments, as well as for required pharmacogenomic studies
Activated partial thromboplastin time (APTT) < 1.2 times upper limit of normal (ULN); (Note: use of warfarin is prohibited; low molecular weight heparin is allowed, so long as these criteria are met)
Platelet (PLT) = 100,000/uL
Histologic proof of cancer which is now not amenable to alternative curative or clearly superior standard treatment options
Life expectancy >= 84 days (3 months)
Women of childbearing potential only: negative serum pregnancy test done =< 14 days prior to registration

Exclusion Criteria

Biologic therapy =< 28 days prior to registration
Blood pressure (BP) > 140 mmHg (systolic) and > 90 mmHg (diastolic); initiation or adjustment of BP medication is permitted prior to registration provided that the average of three BP readings at a visit prior to registration is < 140/90 mmHg
Receiving any other investigational agent
...
Biologic therapy =< 28 days prior to registration
Blood pressure (BP) > 140 mmHg (systolic) and > 90 mmHg (diastolic); initiation or adjustment of BP medication is permitted prior to registration provided that the average of three BP readings at a visit prior to registration is < 140/90 mmHg
Receiving any other investigational agent
History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to beginning study treatment
Cardiac angioplasty or stenting
Immunotherapy =< 28 days prior to registration
Corrected QT interval (QTc) >= 480 msec and/or receiving any concomitant medications that are associated with a risk of QTc prolongation and/or torsades de pointes; NOTE: these medications should be discontinued or replaced with drugs that do not carry these risks
Active peptic ulcer disease
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
History of bleeding disorder, including patients afflicted with hemophilia, disseminated intravascular coagulation, or any other abnormality of coagulation potentially predisposing patients to bleeding
Failure to fully recover from acute, reversible effects of prior chemotherapy (other anti-neoplastic therapy) and radiation therapy
Pulmonary embolism, untreated deep venous thrombosis (DVT) or DVT which has been treated with therapeutic anticoagulation for less than 6 weeks
History of hemoptysis in excess of 2.5 mL (1/2 teaspoon ) within 8 weeks prior to first dose of study drug
Radiation therapy =< 28 days prior to registration
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
HIV-positive patients on combination antiretroviral therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
Symptomatic peripheral vascular disease
Other active malignancy =< 3 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history or prior malignancy, they must not be receiving other specific treatment (e.g. hormonal or chemotherapy) for their cancer
Subjects with known brain metastases
Myocardial infarction
Men or women of childbearing potential who are unwilling to employ adequate contraception
Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation
Receiving any medications or substances that are inducers of CYP3A4 (efavirenz, nevirapine, carbamazepine, modafinil, phenobarbital, phenytoin, pioglitazone, rifabutin, rifampin, St. John's wort); use of the aforementioned inducers is prohibited =< 7 days prior to registration
Coronary artery bypass graft surgery
Nursing women
Serious or non-healing wound, ulcer, or bone fracture
Receiving mitotane within 6 months of enrolling on the study
Poorly controlled depression or anxiety disorder, or recent (=< 6 months) suicidal ideation
Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; a subject who has a history of class II heart failure and is asymptomatic on treatment may be considered eligible
Ejection fraction < institutional lower limit of normal (LLN) and/or history of cardiomyopathy
Pregnant women
Receiving a medication with known risk of torsades de pointes; the following medications are specifically prohibited: amiodarone, arsenic trioxide, bepridil, chloroquine, chlorpromazine, cisapride, clarithromycin, disopyramide, dofetilide, dolasetron, droperidol, erythromycin, halofantrine, haloperidol, ibutilide levomethadyl, mesoridazine, methadone, pentamidine, pimozide, procainamide, quinidine, sotalol, sparfloxacin, and thioridazine; patients should be watched carefully for indications of torsades de pointes, such as syncope; performing additional electrocardiograms (EKGs) on subjects who must take one or more of these medications is not required; however, additional investigations, including EKGs, may be performed as per the treating physician's judgment
Mitomycin C/nitrosoureas =< 42 days prior to registration
Prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel
Chemotherapy =< 28 days prior to registration
Current use of therapeutic warfarin; Note: low molecular weight heparin is allowed; prothrombin time (PT)/partial thromboplastin time (PTT) must meet the inclusion criteria
Any lesion, whether induced by tumor, radiation or other conditions, which makes it difficult to swallow capsules or pills
Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 counts < 200
Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
Arterial thrombosis
Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
Known intraluminal metastatic lesions
Receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) (indinavir, nelfinavir, atazanavir, ritonavir, clarithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, saquinavir, telithromycin, aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil, diltiazem); use of the aforementioned strong or moderate inhibitors is prohibited < 7 days prior to registration
Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation); Note: concomitant use of zoledronic acid, pamidronate or denosumab is allowed (and can be initiated while patients are on study therapy at investigator discretion)
Radiation to > 25% of bone marrow
Admission for unstable angina
Prior use of pazopanib (prior use of other kinase inhibitors allowed)
Active peptic ulcer disease
Active cardiac arrhythmia (except sinus arrhythmia, atrial fibrillation, asymptomatic premature ventricular contractions [PVCs])
Malabsorption syndrome

Tracking Information

NCT #
NCT01552356
Collaborators
Not Provided
Investigators
  • Principal Investigator: Keith C Bible Mayo Clinic
  • Keith C Bible Mayo Clinic
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