This randomized phase II trial studies how well pazopanib hydrochloride with or without ascorbic acid work in treating patients with kidney cancer that has spread to other places in the body (metastatic) or cannot be removed by surgery. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ascorbic acid may help pazopanib hydrochloride stop tumor growth and improve treatment survival. Giving pazopanib hydrochloride and ascorbic acid may work better in treating patients with kidney cancer.
PRIMARY OBJECTIVES: I. To estimate and compare treatment failure-free rate at 40 weeks from randomization of patients with unresectable/metastatic clear cell renal cell carcinoma (ccRCC) receiving one of the following regimens: Arm A: pazopanib hydrochloride (pazopanib) 800 mg daily plus intravenous (IV) ascorbic acid 1g/kg 3 times/week and Arm B: pazopanib 800 mg daily. SECONDARY OBJECTIVES: I. To estimate and compare the overall survival (OS) in patients receiving pazopanib with or without IV ascorbic acid. II. To estimate and compare the progression-free survival (PFS) in patients receiving pazopanib with or without IV ascorbic acid. III. To estimate and compare the overall response rate (ORR) in patients receiving pazopanib with or without IV ascorbic acid. IV. To estimate and compare the duration on pazopanib treatment in patients receiving pazopanib with or without IV ascorbic acid. V. To assess the adverse events (AE) profile and safety of each treatment arm using the Common Terminology Criteria for Adverse Events (CTCAE). CORRELATIVE RESEARCH: I. Correlation between 5 mC, 5 hmC and H3K27me3 expression (as determined by immunohistochemistry \[IHC\]), as well as MeDIP/hMeDIP sequencing (seq), and response to combination of IV ascorbic acid and pazopanib. II. Correlation between iron content in tumor microenvironment (as determined by Prussian blue staining) and response to combination of IV ascorbic acid and pazopanib combination. III. Correlation between HIF-1alpha and HIF-2alpha expression (as determined by immunohistochemistry \[IHC\]) and response to combination of IV ascorbic acid and pazopanib combination. IV. Correlation between GLUT1 expression (as determined by IHC) and response to combination of IV ascorbic acid and pazopanib. V. Correlation between PDL1 expression (as determined by IHC) and response to combination of IV ascorbic acid and pazopanib. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28 and ascorbic acid IV three times per week. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive pazopanib hydrochloride PO QD on days 1-28. Treatment repeats every 28 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 8 weeks for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
5
Given IV
Given PO
Illinois CancerCare-Peoria
Peoria, Illinois, United States
Carle Cancer Center
Urbana, Illinois, United States
Mayo Clinic
Rochester, Minnesota, United States
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, United States
Sanford Medical Center Fargo
Fargo, North Dakota, United States
Treatment Failure-free Rate
Treatment failure is defined as any of the following: radiographic disease progression, off-protocol treatment due to adverse event, initiation of alternative therapy (except metastasectomy post clinical benefit (complete response \[CR\], partial response \[PR\], or stable disease \[SD\] per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 to treatment), and death due to any cause.
Time frame: At 40 weeks
Overall Survival
Will be estimated using the method of Kaplan-Meier and be compared using log rank tests.
Time frame: 26 months
Progression Free Survival
Will be estimated using the Kaplan-Meier method.
Time frame: 16 Months
Overall Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan, PET/CT, or MRI: Complete Response (CR), Disappearance of all target lesions and all target lymph nodes must have reduction in short axis to \<1.0 cm; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation; Overall Response (OR) = CR + PR. Will be compared using a Chi-Square test.
Time frame: 16 Months
Duration of Time on Pazopanib Hydrochloride
Will be described as the median time on treatment by arm.
Time frame: 10 months
Frequency of Adverse Events
Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Adverse events and toxicities will be evaluated using all patients who have received any study treatment as well as summarizing those who have been included in the efficacy analyses. The overall adverse event frequencies for grade 3 or higher adverse events, will be compared using Chi-Square tests between the 2 treatment arms.
Time frame: 10 Months
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