Pazopanib Hydrochloride in Treating Patients With Advanced or Refractory Solid Tumors
Last updated on April 2022Recruitment
- Recruitment Status
- Active, not recruiting
- Estimated Enrollment
- 30
Inclusion Criteria
- Absolute neutrophil count (ANC) >= 1,500/uL
- Urine protein/creatinine ratio < 1 or 24-hour urine < 1 gram
- Measurable disease
- ...
- Absolute neutrophil count (ANC) >= 1,500/uL
- Urine protein/creatinine ratio < 1 or 24-hour urine < 1 gram
- Measurable disease
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X ULN
- Ability to provide informed consent
- 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)
- < Grade 3 hypo/hypercalcemia
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- < Grade 3 hypo/hypermagnesemia
- 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)
- Women of childbearing potential only: negative serum pregnancy test done =< 14 days prior to registration
- Creatinine =< 1.5 times ULN OR measured creatinine clearance of >= 60 mL/min 1.73 m^2
- 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)
- < Grade 3 hypo/hyperphosphatemia
- Hemoglobin (Hgb) >= 8.0 g/dL
- Willingness to provide mandatory blood samples for pazopanib drug level assessments required for dosage adjustments, as well as for required pharmacogenomic studies
- < Grade 2 hypo/hyperkalemia
- Direct bilirubin =< 1.5 X upper limit of normal (ULN) (subjects with Gilbert's syndrome and elevations of indirect bilirubin only are eligible)
- Willing to return to Mayo Clinic for follow up
Exclusion Criteria
- Coronary artery bypass graft surgery
- Prior use of pazopanib (prior use of other kinase inhibitors allowed)
- 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
- ...
- Coronary artery bypass graft surgery
- Prior use of pazopanib (prior use of other kinase inhibitors allowed)
- 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
- 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
- Poorly controlled depression or anxiety disorder, or recent (=< 6 months) suicidal ideation
- Receiving any other investigational agent
- Active cardiac arrhythmia (except sinus arrhythmia, atrial fibrillation, asymptomatic premature ventricular contractions [PVCs])
- 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
- Pulmonary embolism, untreated deep venous thrombosis (DVT) or DVT which has been treated with therapeutic anticoagulation for less than 6 weeks
- Mitomycin C/nitrosoureas =< 42 days prior to registration
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to beginning study treatment
- Active peptic ulcer disease
- Immunotherapy =< 28 days prior to registration
- Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation
- Serious or non-healing wound, ulcer, or bone fracture
- 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
- Failure to fully recover from acute, reversible effects of prior chemotherapy (other anti-neoplastic therapy) and radiation therapy
- HIV-positive patients on combination antiretroviral therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
- 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
- Active peptic ulcer disease
- 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)
- History of bleeding disorder, including patients afflicted with hemophilia, disseminated intravascular coagulation, or any other abnormality of coagulation potentially predisposing patients to bleeding
- Pregnant women
- Ejection fraction < institutional lower limit of normal (LLN) and/or history of cardiomyopathy
- Radiation therapy =< 28 days prior to registration
- Prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel
- Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
- Symptomatic peripheral vascular disease
- 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
- Receiving mitotane within 6 months of enrolling on the study
- 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
- Radiation to > 25% of bone marrow
- 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
- Myocardial infarction
- Current use of therapeutic warfarin; Note: low molecular weight heparin is allowed; prothrombin time (PT)/partial thromboplastin time (PTT) must meet the inclusion criteria
- Known intraluminal metastatic lesions
- Arterial thrombosis
- Men or women of childbearing potential who are unwilling to employ adequate contraception
- Admission for unstable angina
- 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
- History of hemoptysis in excess of 2.5 mL (1/2 teaspoon ) within 8 weeks prior to first dose of study drug
- Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
- Nursing women
- Subjects with known brain metastases
- Cardiac angioplasty or stenting
- 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
- Malabsorption syndrome
- Chemotherapy =< 28 days prior to registration
- Biologic therapy =< 28 days prior to registration
- Any lesion, whether induced by tumor, radiation or other conditions, which makes it difficult to swallow capsules or pills
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
- Absolute neutrophil count (ANC) >= 1,500/uL
- Urine protein/creatinine ratio < 1 or 24-hour urine < 1 gram
- Measurable disease
- ...
- Absolute neutrophil count (ANC) >= 1,500/uL
- Urine protein/creatinine ratio < 1 or 24-hour urine < 1 gram
- Measurable disease
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X ULN
- Ability to provide informed consent
- 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)
- < Grade 3 hypo/hypercalcemia
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- < Grade 3 hypo/hypermagnesemia
- 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)
- Women of childbearing potential only: negative serum pregnancy test done =< 14 days prior to registration
- Creatinine =< 1.5 times ULN OR measured creatinine clearance of >= 60 mL/min 1.73 m^2
- 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)
- < Grade 3 hypo/hyperphosphatemia
- Hemoglobin (Hgb) >= 8.0 g/dL
- Willingness to provide mandatory blood samples for pazopanib drug level assessments required for dosage adjustments, as well as for required pharmacogenomic studies
- < Grade 2 hypo/hyperkalemia
- Direct bilirubin =< 1.5 X upper limit of normal (ULN) (subjects with Gilbert's syndrome and elevations of indirect bilirubin only are eligible)
- Willing to return to Mayo Clinic for follow up
Exclusion Criteria
- Coronary artery bypass graft surgery
- Prior use of pazopanib (prior use of other kinase inhibitors allowed)
- 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
- ...
- Coronary artery bypass graft surgery
- Prior use of pazopanib (prior use of other kinase inhibitors allowed)
- 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
- 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
- Poorly controlled depression or anxiety disorder, or recent (=< 6 months) suicidal ideation
- Receiving any other investigational agent
- Active cardiac arrhythmia (except sinus arrhythmia, atrial fibrillation, asymptomatic premature ventricular contractions [PVCs])
- 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
- Pulmonary embolism, untreated deep venous thrombosis (DVT) or DVT which has been treated with therapeutic anticoagulation for less than 6 weeks
- Mitomycin C/nitrosoureas =< 42 days prior to registration
- History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to beginning study treatment
- Active peptic ulcer disease
- Immunotherapy =< 28 days prior to registration
- Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation
- Serious or non-healing wound, ulcer, or bone fracture
- 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
- Failure to fully recover from acute, reversible effects of prior chemotherapy (other anti-neoplastic therapy) and radiation therapy
- HIV-positive patients on combination antiretroviral therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
- 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
- Active peptic ulcer disease
- 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)
- History of bleeding disorder, including patients afflicted with hemophilia, disseminated intravascular coagulation, or any other abnormality of coagulation potentially predisposing patients to bleeding
- Pregnant women
- Ejection fraction < institutional lower limit of normal (LLN) and/or history of cardiomyopathy
- Radiation therapy =< 28 days prior to registration
- Prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel
- Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
- Symptomatic peripheral vascular disease
- 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
- Receiving mitotane within 6 months of enrolling on the study
- 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
- Radiation to > 25% of bone marrow
- 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
- Myocardial infarction
- Current use of therapeutic warfarin; Note: low molecular weight heparin is allowed; prothrombin time (PT)/partial thromboplastin time (PTT) must meet the inclusion criteria
- Known intraluminal metastatic lesions
- Arterial thrombosis
- Men or women of childbearing potential who are unwilling to employ adequate contraception
- Admission for unstable angina
- 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
- History of hemoptysis in excess of 2.5 mL (1/2 teaspoon ) within 8 weeks prior to first dose of study drug
- Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
- Nursing women
- Subjects with known brain metastases
- Cardiac angioplasty or stenting
- 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
- Malabsorption syndrome
- Chemotherapy =< 28 days prior to registration
- Biologic therapy =< 28 days prior to registration
- Any lesion, whether induced by tumor, radiation or other conditions, which makes it difficult to swallow capsules or pills
Tracking Information
- NCT #
- NCT01552356
- Collaborators
- Not Provided
- Investigators
- Principal Investigator: Keith C Bible Mayo Clinic
- Keith C Bible Mayo Clinic