Brief Summary
This randomized phase III trial studies how well pazopanib hydrochloride works compared to placebo in treating patients with kidney cancer that has spread to other parts of the body and have no evidence of disease after surgery. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
Brief Title
Pazopanib Hydrochloride in Treating Patients With Metastatic Kidney Cancer Who Have No Evidence of Disease After Surgery
Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate disease-free survival with pazopanib (pazopanib hydrochloride) as compared to placebo, defined as the time from randomization to the development of recurrent disease, second primary cancer (other than localized breast, localized prostate, or non-melanoma skin cancer) or death from any cause for patients with metastatic renal cell carcinoma (RCC) with no evidence of disease following metastasectomy.
SECONDARY OBJECTIVES:
I. To describe the overall survival of patients with advanced RCC randomly assigned to receive placebo or pazopanib for one year following metastasectomy to no evidence of disease (NED).
II. To describe treatment and (at recurrence) disease-related adverse events in the two treatment arms.
III. To analyze quality-adjusted time without symptoms of disease or treatment (Q-TWiST) for subjects in the two treatment arms.
IV. To characterize changes in patient-reported fatigue and (at recurrence) kidney cancer-related symptoms during and following treatment with pazopanib compared to placebo.
V. To explore the association between plasma trough levels of pazopanib and disease-free and overall survival.
VI. To prospectively bank preserved tissue from primary tumors and associated metastatic sites in patients with RCC.
OUTLINE: Patients are randomized to 1of 2 treatment arms.
ARM A: Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive placebo PO QD on days 1-28. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study.
After completion of study treatment, patients are followed up every 3 months for the first two years, every 6 months for the next 3 years, and then annually up to 10 years.
I. To evaluate disease-free survival with pazopanib (pazopanib hydrochloride) as compared to placebo, defined as the time from randomization to the development of recurrent disease, second primary cancer (other than localized breast, localized prostate, or non-melanoma skin cancer) or death from any cause for patients with metastatic renal cell carcinoma (RCC) with no evidence of disease following metastasectomy.
SECONDARY OBJECTIVES:
I. To describe the overall survival of patients with advanced RCC randomly assigned to receive placebo or pazopanib for one year following metastasectomy to no evidence of disease (NED).
II. To describe treatment and (at recurrence) disease-related adverse events in the two treatment arms.
III. To analyze quality-adjusted time without symptoms of disease or treatment (Q-TWiST) for subjects in the two treatment arms.
IV. To characterize changes in patient-reported fatigue and (at recurrence) kidney cancer-related symptoms during and following treatment with pazopanib compared to placebo.
V. To explore the association between plasma trough levels of pazopanib and disease-free and overall survival.
VI. To prospectively bank preserved tissue from primary tumors and associated metastatic sites in patients with RCC.
OUTLINE: Patients are randomized to 1of 2 treatment arms.
ARM A: Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive placebo PO QD on days 1-28. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.
Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study.
After completion of study treatment, patients are followed up every 3 months for the first two years, every 6 months for the next 3 years, and then annually up to 10 years.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Clear Cell Renal Cell Carcinoma
Stage IV Renal Cell Cancer AJCC v7
Eligibility Criteria
Inclusion Criteria:
* Patient must be at least 18 years of age at the time of randomization
* Patient must have pathologically confirmed renal cell carcinoma with a clear cell component; pure papillary and chromophobe histologies are excluded; there must be pathologic confirmation of metastatic disease in the resected metastasectomy specimen
* Patient must have undergone nephrectomy or partial nephrectomy to remove primary renal cell carcinoma (at any time in the past)
* Patient must have undergone surgical resection to remove one or more sites of metastatic disease, with successful removal of all known sites 2-12 weeks prior to randomization. Any number of prior metastasectomies may have been performed in the past, so long as the most recent procedure was within the 12 weeks of registration. The most recent procedure may be nephrectomy for a renal primary tumor
* Patients with synchronous disease at initial diagnosis must have metastatic (M1) disease (American Joint Committee on Cancer \[AJCC\] 7th edition T1-4N0-1M1)
* Positive surgical margins are permitted if the surgeon confirms complete resection of gross metastatic disease, and post-operative scans are negative
* Patients presenting with metachronous disease may have distant metastases, regional lymph node or renal bed recurrence. Recurrences at a partial nephrectomy resection site are not eligible if it is the only site of disease
* Patient must have no evidence of disease on post-operative imaging:
* A computed tomography (CT) of the chest must be obtained within 4 weeks prior to randomization with or without contrast
* A CT of the abdomen/pelvis must be obtained within 4 weeks prior to randomization with intravenous (IV) contrast (oral contrast may be added at the radiologist's discretion); an magnetic resonance imaging (MRI) of the abdomen/pelvis with gadolinium may be substituted for the CT if the CT with IV contrast is contra-indicated
* An MRI of the brain with and without gadolinium must be done within 8 weeks prior to randomization; a CT of the brain with and without IV contrast is permitted if MRI is contra-indicated (i.e., pacemaker)
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the time of randomization
* Absolute granulocyte count \> 1,500/mcL (within 2 weeks prior to randomization)
* Platelets \> 100,000/mcL (within 2 weeks prior to randomization)
* Total bilirubin \< 1.5 x institutional upper limit of normal (ULN) (within 2 weeks prior to randomization)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 x upper limit of normal (ULN) (within 2 weeks prior to randomization)
* Calculated creatinine clearance (CrCl) \> 30 mL/min (within 2 weeks prior to randomization)
* Subjects must have a urine protein/creatinine (UPC) ratio \< 1; if UPC \>= 1, then a 24-hour urine total protein must be obtained; subjects must have a 24-hour urine protein value \< 1 g to be eligible; use of urine dipstick for renal function assessment is not acceptable (within 2 weeks prior to randomization)
* All females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately
* Patient must be able to swallow pills and have no significant impairment in gastrointestinal absorption including history of gastric bypass surgery
* Patient must have a corrected QT (QTc) interval on electrocardiogram (ECG) =\< 0.48 seconds by Bazett's calculation (=\< Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v.\]4 grade 2) prior to randomization
* Patient must have a systolic blood pressure =\< 140 mmHg and diastolic blood pressure must be =\< 90 mmHg, measured within 4 weeks prior to randomization; initiation or adjustment of anti-hypertensives prior to starting study treatment is allowed
* Patient must have no history of cerebrovascular accident (CVA) within 6 months of randomization
Exclusion Criteria:
* Patients presenting with tumors within the kidneys (multiple synchronous or single/multiple metachronous) are not eligible if there are no extrarenal sites of disease (i.e. potential multifocal primary disease)
* Patient must not have received any prior or concurrent systemic therapy for RCC. Adjuvant placebo administration is permitted
* Patient must have no active peptic ulcer disease
* Patient must have no active inflammatory bowel disease
* Patient must have no New York Heart Association (NYHA) class II or greater congestive heart failure
* Patient must have no prior history or current clinically apparent central nervous system metastases
* Women must not be pregnant or breast-feeding due to the unknown effects of pazopanib on the developing fetus
* Patient must have no history of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib
* Patient must have no 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
* Patient must not have serious or non-healing wound, ulcer, or bone fracture at the time of randomization
* Patient must have no history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to randomization
* Patient must have no history of myocardial infarction, hospital admission for unstable angina, cardiac angioplasty or stenting within 6 months of randomization
* Patient must have no history venous thrombosis within 12 weeks of randomization
* Patient cannot be taking strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors such as:
* Antibiotics: clarithromycin, telithromycin, troleandomycin
* Human immunodeficiency virus (HIV) antiviral protease inhibitors: ritonavir, indinavir, saquinavir, nelfinavir, amprenavir, lopinavir
* Antifungals: itraconazole, ketoconazole, voriconazole, fluconazole
* Antidepressants: nefazodone
* Patient must not have history of hemoptysis in excess of 2.5 mL (1/2 teaspoon) within 8 weeks prior to randomization
* Patient must not be taking drugs known to prolong the QTc interval; such drugs should be discontinued at least 5 half-lives prior to randomization
* Patients must not have any history of other cancer within 3 years from time of randomization with the exception of basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or resected non-invasive (Ta) urothelial carcinoma
* Patient must be at least 18 years of age at the time of randomization
* Patient must have pathologically confirmed renal cell carcinoma with a clear cell component; pure papillary and chromophobe histologies are excluded; there must be pathologic confirmation of metastatic disease in the resected metastasectomy specimen
* Patient must have undergone nephrectomy or partial nephrectomy to remove primary renal cell carcinoma (at any time in the past)
* Patient must have undergone surgical resection to remove one or more sites of metastatic disease, with successful removal of all known sites 2-12 weeks prior to randomization. Any number of prior metastasectomies may have been performed in the past, so long as the most recent procedure was within the 12 weeks of registration. The most recent procedure may be nephrectomy for a renal primary tumor
* Patients with synchronous disease at initial diagnosis must have metastatic (M1) disease (American Joint Committee on Cancer \[AJCC\] 7th edition T1-4N0-1M1)
* Positive surgical margins are permitted if the surgeon confirms complete resection of gross metastatic disease, and post-operative scans are negative
* Patients presenting with metachronous disease may have distant metastases, regional lymph node or renal bed recurrence. Recurrences at a partial nephrectomy resection site are not eligible if it is the only site of disease
* Patient must have no evidence of disease on post-operative imaging:
* A computed tomography (CT) of the chest must be obtained within 4 weeks prior to randomization with or without contrast
* A CT of the abdomen/pelvis must be obtained within 4 weeks prior to randomization with intravenous (IV) contrast (oral contrast may be added at the radiologist's discretion); an magnetic resonance imaging (MRI) of the abdomen/pelvis with gadolinium may be substituted for the CT if the CT with IV contrast is contra-indicated
* An MRI of the brain with and without gadolinium must be done within 8 weeks prior to randomization; a CT of the brain with and without IV contrast is permitted if MRI is contra-indicated (i.e., pacemaker)
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the time of randomization
* Absolute granulocyte count \> 1,500/mcL (within 2 weeks prior to randomization)
* Platelets \> 100,000/mcL (within 2 weeks prior to randomization)
* Total bilirubin \< 1.5 x institutional upper limit of normal (ULN) (within 2 weeks prior to randomization)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 x upper limit of normal (ULN) (within 2 weeks prior to randomization)
* Calculated creatinine clearance (CrCl) \> 30 mL/min (within 2 weeks prior to randomization)
* Subjects must have a urine protein/creatinine (UPC) ratio \< 1; if UPC \>= 1, then a 24-hour urine total protein must be obtained; subjects must have a 24-hour urine protein value \< 1 g to be eligible; use of urine dipstick for renal function assessment is not acceptable (within 2 weeks prior to randomization)
* All females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately
* Patient must be able to swallow pills and have no significant impairment in gastrointestinal absorption including history of gastric bypass surgery
* Patient must have a corrected QT (QTc) interval on electrocardiogram (ECG) =\< 0.48 seconds by Bazett's calculation (=\< Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v.\]4 grade 2) prior to randomization
* Patient must have a systolic blood pressure =\< 140 mmHg and diastolic blood pressure must be =\< 90 mmHg, measured within 4 weeks prior to randomization; initiation or adjustment of anti-hypertensives prior to starting study treatment is allowed
* Patient must have no history of cerebrovascular accident (CVA) within 6 months of randomization
Exclusion Criteria:
* Patients presenting with tumors within the kidneys (multiple synchronous or single/multiple metachronous) are not eligible if there are no extrarenal sites of disease (i.e. potential multifocal primary disease)
* Patient must not have received any prior or concurrent systemic therapy for RCC. Adjuvant placebo administration is permitted
* Patient must have no active peptic ulcer disease
* Patient must have no active inflammatory bowel disease
* Patient must have no New York Heart Association (NYHA) class II or greater congestive heart failure
* Patient must have no prior history or current clinically apparent central nervous system metastases
* Women must not be pregnant or breast-feeding due to the unknown effects of pazopanib on the developing fetus
* Patient must have no history of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib
* Patient must have no 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
* Patient must not have serious or non-healing wound, ulcer, or bone fracture at the time of randomization
* Patient must have no history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to randomization
* Patient must have no history of myocardial infarction, hospital admission for unstable angina, cardiac angioplasty or stenting within 6 months of randomization
* Patient must have no history venous thrombosis within 12 weeks of randomization
* Patient cannot be taking strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors such as:
* Antibiotics: clarithromycin, telithromycin, troleandomycin
* Human immunodeficiency virus (HIV) antiviral protease inhibitors: ritonavir, indinavir, saquinavir, nelfinavir, amprenavir, lopinavir
* Antifungals: itraconazole, ketoconazole, voriconazole, fluconazole
* Antidepressants: nefazodone
* Patient must not have history of hemoptysis in excess of 2.5 mL (1/2 teaspoon) within 8 weeks prior to randomization
* Patient must not be taking drugs known to prolong the QTc interval; such drugs should be discontinued at least 5 half-lives prior to randomization
* Patients must not have any history of other cancer within 3 years from time of randomization with the exception of basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or resected non-invasive (Ta) urothelial carcinoma
Inclusion Criteria
Inclusion Criteria:
* Patient must be at least 18 years of age at the time of randomization
* Patient must have pathologically confirmed renal cell carcinoma with a clear cell component; pure papillary and chromophobe histologies are excluded; there must be pathologic confirmation of metastatic disease in the resected metastasectomy specimen
* Patient must have undergone nephrectomy or partial nephrectomy to remove primary renal cell carcinoma (at any time in the past)
* Patient must have undergone surgical resection to remove one or more sites of metastatic disease, with successful removal of all known sites 2-12 weeks prior to randomization. Any number of prior metastasectomies may have been performed in the past, so long as the most recent procedure was within the 12 weeks of registration. The most recent procedure may be nephrectomy for a renal primary tumor
* Patients with synchronous disease at initial diagnosis must have metastatic (M1) disease (American Joint Committee on Cancer \[AJCC\] 7th edition T1-4N0-1M1)
* Positive surgical margins are permitted if the surgeon confirms complete resection of gross metastatic disease, and post-operative scans are negative
* Patients presenting with metachronous disease may have distant metastases, regional lymph node or renal bed recurrence. Recurrences at a partial nephrectomy resection site are not eligible if it is the only site of disease
* Patient must have no evidence of disease on post-operative imaging:
* A computed tomography (CT) of the chest must be obtained within 4 weeks prior to randomization with or without contrast
* A CT of the abdomen/pelvis must be obtained within 4 weeks prior to randomization with intravenous (IV) contrast (oral contrast may be added at the radiologist's discretion); an magnetic resonance imaging (MRI) of the abdomen/pelvis with gadolinium may be substituted for the CT if the CT with IV contrast is contra-indicated
* An MRI of the brain with and without gadolinium must be done within 8 weeks prior to randomization; a CT of the brain with and without IV contrast is permitted if MRI is contra-indicated (i.e., pacemaker)
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the time of randomization
* Absolute granulocyte count \> 1,500/mcL (within 2 weeks prior to randomization)
* Platelets \> 100,000/mcL (within 2 weeks prior to randomization)
* Total bilirubin \< 1.5 x institutional upper limit of normal (ULN) (within 2 weeks prior to randomization)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 x upper limit of normal (ULN) (within 2 weeks prior to randomization)
* Calculated creatinine clearance (CrCl) \> 30 mL/min (within 2 weeks prior to randomization)
* Subjects must have a urine protein/creatinine (UPC) ratio \< 1; if UPC \>= 1, then a 24-hour urine total protein must be obtained; subjects must have a 24-hour urine protein value \< 1 g to be eligible; use of urine dipstick for renal function assessment is not acceptable (within 2 weeks prior to randomization)
* All females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately
* Patient must be able to swallow pills and have no significant impairment in gastrointestinal absorption including history of gastric bypass surgery
* Patient must have a corrected QT (QTc) interval on electrocardiogram (ECG) =\< 0.48 seconds by Bazett's calculation (=\< Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v.\]4 grade 2) prior to randomization
* Patient must have a systolic blood pressure =\< 140 mmHg and diastolic blood pressure must be =\< 90 mmHg, measured within 4 weeks prior to randomization; initiation or adjustment of anti-hypertensives prior to starting study treatment is allowed
* Patient must have no history of cerebrovascular accident (CVA) within 6 months of randomization
* Patient must be at least 18 years of age at the time of randomization
* Patient must have pathologically confirmed renal cell carcinoma with a clear cell component; pure papillary and chromophobe histologies are excluded; there must be pathologic confirmation of metastatic disease in the resected metastasectomy specimen
* Patient must have undergone nephrectomy or partial nephrectomy to remove primary renal cell carcinoma (at any time in the past)
* Patient must have undergone surgical resection to remove one or more sites of metastatic disease, with successful removal of all known sites 2-12 weeks prior to randomization. Any number of prior metastasectomies may have been performed in the past, so long as the most recent procedure was within the 12 weeks of registration. The most recent procedure may be nephrectomy for a renal primary tumor
* Patients with synchronous disease at initial diagnosis must have metastatic (M1) disease (American Joint Committee on Cancer \[AJCC\] 7th edition T1-4N0-1M1)
* Positive surgical margins are permitted if the surgeon confirms complete resection of gross metastatic disease, and post-operative scans are negative
* Patients presenting with metachronous disease may have distant metastases, regional lymph node or renal bed recurrence. Recurrences at a partial nephrectomy resection site are not eligible if it is the only site of disease
* Patient must have no evidence of disease on post-operative imaging:
* A computed tomography (CT) of the chest must be obtained within 4 weeks prior to randomization with or without contrast
* A CT of the abdomen/pelvis must be obtained within 4 weeks prior to randomization with intravenous (IV) contrast (oral contrast may be added at the radiologist's discretion); an magnetic resonance imaging (MRI) of the abdomen/pelvis with gadolinium may be substituted for the CT if the CT with IV contrast is contra-indicated
* An MRI of the brain with and without gadolinium must be done within 8 weeks prior to randomization; a CT of the brain with and without IV contrast is permitted if MRI is contra-indicated (i.e., pacemaker)
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at the time of randomization
* Absolute granulocyte count \> 1,500/mcL (within 2 weeks prior to randomization)
* Platelets \> 100,000/mcL (within 2 weeks prior to randomization)
* Total bilirubin \< 1.5 x institutional upper limit of normal (ULN) (within 2 weeks prior to randomization)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2.5 x upper limit of normal (ULN) (within 2 weeks prior to randomization)
* Calculated creatinine clearance (CrCl) \> 30 mL/min (within 2 weeks prior to randomization)
* Subjects must have a urine protein/creatinine (UPC) ratio \< 1; if UPC \>= 1, then a 24-hour urine total protein must be obtained; subjects must have a 24-hour urine protein value \< 1 g to be eligible; use of urine dipstick for renal function assessment is not acceptable (within 2 weeks prior to randomization)
* All females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; if a man impregnates a woman while participating in this study, he should inform his treating physician immediately
* Patient must be able to swallow pills and have no significant impairment in gastrointestinal absorption including history of gastric bypass surgery
* Patient must have a corrected QT (QTc) interval on electrocardiogram (ECG) =\< 0.48 seconds by Bazett's calculation (=\< Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v.\]4 grade 2) prior to randomization
* Patient must have a systolic blood pressure =\< 140 mmHg and diastolic blood pressure must be =\< 90 mmHg, measured within 4 weeks prior to randomization; initiation or adjustment of anti-hypertensives prior to starting study treatment is allowed
* Patient must have no history of cerebrovascular accident (CVA) within 6 months of randomization
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01575548
Org Class
Nih
Org Full Name
National Cancer Institute (NCI)
Org Study Id
NCI-2012-00723
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Randomized, Double-Blind Phase III Study of Pazopanib vs. Placebo in Patients With Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease Following Metastatectomy
Primary Outcomes
Outcome Description
Disease-free survival (DFS) is defined as the time from randomization to the development of recurrent disease, second primary cancer (other than localized breast, localized prostate, or non-melanoma skin cancer) or death from any cause.
Outcome Measure
Disease-free Survival (DFS)
Outcome Time Frame
Assessed every 3 months for the first 2 years, every 6 months for the next 3 years, and then annually up to 6 years
Secondary Ids
Secondary Id
NCI-2012-00723
Secondary Id
CDR0000730383
Secondary Id
ECOG-E2810
Secondary Id
E2810
Secondary Id
E2810
Secondary Id
E2810
Secondary Id
U10CA021115
Secondary Id
U10CA180820
Secondary Id
U10CA180830
Secondary Id
U24CA196172
Secondary Outcomes
Outcome Description
Overall survival is defined as the time from randomization to death or date last known alive. Kaplan-Meier method was used to estimate 3-year overall survival rate.
Outcome Time Frame
Assessed every 3 months for the first 2 years, and then every 6 months for the 3rd year.
Outcome Measure
3-year Overall Survival (OS) Rate
Outcome Description
OS for each arm is divided into 3 health states: toxicity (TOX), time without symptoms of disease or toxicity (TWiST), and recurrence (REC). TOX is defined as the time spent with grade 3/4 adverse events (AEs) prior to disease recurrence. TWiST is defined as the time prior to disease recurrence when no AEs of grade 3/4 were experienced. REC health state is defined as the time from disease recurrence or second primary cancer until death. Patients alive will be censored at the date of last contact. For each health state, a patient-reported utility weight will be assigned. The mean amount of time in each state will be estimated using Kaplan and Meier method.
TWiST = mean recurrence-free survival (RFS) - mean time with toxicities REC = mean OS - mean RFS Q-TWiST = (uTOX x TOX) + (uTWiST x TWiST) + (uREC x REC) Where uTOX, uTWiST, and uREC represent the average group utility value for each state for that arm and TOX, TWiST and REC represent the mean duration of the state for that arm.
TWiST = mean recurrence-free survival (RFS) - mean time with toxicities REC = mean OS - mean RFS Q-TWiST = (uTOX x TOX) + (uTWiST x TWiST) + (uREC x REC) Where uTOX, uTWiST, and uREC represent the average group utility value for each state for that arm and TOX, TWiST and REC represent the mean duration of the state for that arm.
Outcome Time Frame
Assessed every 3 months for the first 2 years, every 6 months for the next 3 years, then annually up to 10 years
Outcome Measure
Quality-adjusted Time Without Symptoms of Disease or Treatment (Q-TWiST)
Outcome Description
FACIT-Fatigue subscale (13 items) was used to evaluate fatigue in this patient population. The score ranges between 0 and 52. The higher the score, the better the quality of life. The change in FACIT-Fatigue score from baseline to 6 months will be compared between the two arms.
Outcome Time Frame
Assessed at baseline and 6 months
Outcome Measure
Change in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score From Baseline to 6 Months
Outcome Description
Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index - 15 Item Version (FKSI-15) will be used to evaluate the quality of life concerns among this patient population. The change in score from baseline to 6 months will be compared between the two arms. The score ranges between 0 and 60. A score of "0" is a severely symptomatic patient and the highest possible score is an asymptomatic patient.
Outcome Time Frame
Assessed at baseline and 6 months
Outcome Measure
Change in Functional Assessment of Cancer Therapy-Kidney Symptom Index Score From Baseline to 6 Months
Outcome Description
Plasma concentration of pazopanib will be assessed at baseline and cycle 2 day 1.
Outcome Time Frame
Assessed at baseline and cycle 2 day 1
Outcome Measure
Change in Plasma Levels of Pazopanib From Baseline to Cycle 2 Day 1
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Benjamin Gartrell
Investigator Email
bgartrel@montefiore.org
Investigator Phone
718-405-8404