Pazopanib Hydrochloride With or Without Ascorbic Acid in Treating Patients With Kidney Cancer That Is Metastatic or Cannot Be Removed by Surgery

Clear Cell Renal Cell Carcinoma Clinical Trial

Official title: Randomized, Phase II Trial of Intravenous Ascorbic Acid (Vitamin C) as an Adjunct to Pazopanib in the First-Line or Post-Immunotherapy Setting for Metastatic or Unresectable Clear Cell Renal Cell Carcinoma (ccRCC)

Status Terminated

Clinical Trial Summary

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.

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Clear Cell Renal Cell Carcinoma
• Metastatic Clear Cell Renal Cell Carcinoma
• Stage III Renal Cell Cancer AJCC v8
• Stage IV Renal Cell Cancer AJCC v7
• Unresectable Renal Cell Carcinoma

• NCT number: NCT03334409
• Study type: Interventional
• Source: Academic and Community Cancer Research United
• Status: Terminated
• Phase: Phase 2
• Start date: February 16, 2018
• Completion date: March 13, 2021