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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Disease-free Survival (DFS)
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.
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
3-year Overall Survival (OS) Rate
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.
Time frame: Assessed every 3 months for the first 2 years, and then every 6 months for the 3rd year.
Quality-adjusted Time Without Symptoms of Disease or Treatment (Q-TWiST)
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.
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
Change in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score From Baseline to 6 Months
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Purpose
TREATMENT
Masking
DOUBLE
Enrollment
129
Given PO
Ancillary studies
Fairbanks Memorial Hospital
Fairbanks, Alaska, United States
University of Arizona Cancer Center-Orange Grove Campus
Tucson, Arizona, United States
Banner University Medical Center - Tucson
Tucson, Arizona, United States
University of Arizona Cancer Center-North Campus
Tucson, Arizona, United States
CHI Saint Vincent Cancer Center Hot Springs
Hot Springs, Arkansas, United States
PCR Oncology
Arroyo Grande, California, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Epic Care-Dublin
Dublin, California, United States
Bay Area Breast Surgeons Inc
Emeryville, California, United States
Epic Care Partners in Cancer Care
Emeryville, California, United States
...and 571 more locations
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.
Time frame: Assessed at baseline and 6 months
Change in Functional Assessment of Cancer Therapy-Kidney Symptom Index Score From Baseline to 6 Months
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.
Time frame: Assessed at baseline and 6 months
Change in Plasma Levels of Pazopanib From Baseline to Cycle 2 Day 1
Plasma concentration of pazopanib will be assessed at baseline and cycle 2 day 1.
Time frame: Assessed at baseline and cycle 2 day 1