Clinical Trial: Pazopanib Hydrochloride and Bevacizumab in Treating Patients With Previously Untreated Metastatic Kidney Cancer

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase I/II Trial of Pazopanib Alternating With Bevacizumab in Treatment-Naive Metastatic Clear Cell Renal Cell Carcinoma Patients

Brief Summary: This phase I/II trial studies the side effects and best dose of pazopanib hydrochloride and bevacizumab and to see how well they work in treating patients with previously untreated kidney cancer that has spread to other places in the body (metastatic). Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Pazopanib hydrochloride may also stop the growth of tumor cells by blocking blood flow to the tumor. Monoclonal antibodies, such as bevacizumab, can prevent tumor growth by blocking the ability of tumor cells to grow and spread. Giving pazopanib hydrochloride together with bevacizumab may kill more tumor cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the safe phase II dose of this novel regimen. (Phase I) II. To determine the median progression free survival (PFS) from this novel regimen. (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate the safety and toxicity of the proposed regimen. (Phase I) II. To evaluate the response rate. (Phase I) III. To evaluate the pharmacokinetics of pazopanib (pazopanib hydrochloride). (Phase I) IV. To evaluate the vascular endothelial growth factor (VEGF) levels and myeloid derived suppressor cell (MDSC) levels at various time points and correlate with response. (Phase I) V. To evaluate the safety and toxicity of this new regimen. (Phase II) VI. To evaluate the VEGF levels, interleukin (IL)-8 levels and MDSC levels at various time points and correlate with outcome. (Phase II) VII. To evaluate the PFS rate at 12 months. (Phase II) VIII. To evaluate overall survival. (Phase II)

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive pazopanib hydrochloride orally (PO) on days 1-28, and bevacizumab intravenously (IV) over 30-90 minutes on days 36 and 50. Courses repeat every 70 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.


Sponsor: Roswell Park Cancer Institute

Current Primary Outcome:

  • Median PFS (Phase II) [ Time Frame: Up to 30 days post-treatment ]
    Distributions of continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with sub-group associations tested using the Wilcoxon Rank Sum test.
  • Optimal phase II dose, defined as the largest dose level at which less than 2 out of the 6 patients experienced dose-limiting toxicity, graded according to Common Terminology Criteria for Adverse Events version 4.0 (Phase I) [ Time Frame: Up to 140 days ]
    The frequency of toxicities will be tabulated for the dose estimated to be the maximum-tolerated dose.


Original Primary Outcome:

  • Optimal phase II dose defined as the largest dose level at which less than 2 out of the 6 patients experienced dose-limiting toxicity (DLT) assessed based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I) [ Time Frame: Up to 140 days ]
  • Median PFS (Phase II) [ Time Frame: Up to 30 days post-treatment ]
    Distributions of continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with sub-group associations tested using the Wilcoxon Rank Sum test.


Current Secondary Outcome:

  • Incidence of grade 3 or higher toxicities, graded according to CTCAE version 4.0 [ Time Frame: Up to 30 days post-treatment ]
    Categorical variables will be summarized in contingency tables, with associations of interest assessed using Fisher's exact test. The frequency of toxicities will be tabulated by grade across all dose levels and courses.
  • Overall survival (Phase II) [ Time Frame: From the date of study enrollment to the date of death from any cause, assessed up to 30 days post-treatment ]
    Will be obtained using Kaplan-Meier and Proportional Hazards methods.
  • PFS rate at 12 months (Phase II) [ Time Frame: At 12 months ]
    Distributions of continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with sub-group associations tested using the Wilcoxon Rank Sum test.
  • Response rate according to RECIST 1.1 (Phase I) [ Time Frame: Up to 30 days post-treatment ]


Original Secondary Outcome:

  • Incidence of grade 3 or higher toxicities accessed based on CTCAE version 4.0 (Phase I) [ Time Frame: Up to 30 days post-treatment ]
  • Response rate according to RECIST 1.1 (Phase I) [ Time Frame: Up to 30 days post-treatment ]
  • Pharmacokinetics of pazopanib (Phase I) [ Time Frame: Course 1 on day 1 at pre-dose, 2 hours, and 4 hours post-dose; day 15 at pre-dose and 2 hours post-dose; and day 29 ]
  • VEGF levels, IL-8 levels and MDSC levels (Phase I) [ Time Frame: Up to 30 days post-treatment ]
  • Incidence of grade 3 or higher toxicities accessed based on CTCAE version 4.0 (Phase II) [ Time Frame: Up to 30 days post-treatment ]
    Categorical variables will be summarized in contingency tables, with associations of interest assessed using Fisherâs exact test.
  • VEGF levels, IL-8 levels and MDSC levels (Phase II) [ Time Frame: Up to 30 days post-treatment ]
    Distributions of continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with sub-group associations tested using the Wilcoxon Rank Sum test.
  • PFS rate at 12 months (Phase II) [ Time Frame: At 12 months ]
    Distributions of continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with sub-group associations tested using the Wilcoxon Rank Sum test.
  • Overall survival (Phase II) [ Time Frame: From the date of study enrollment to the date of death from any cause, assessed up to 30 days post-treatment ]
    Will be obtained using Kaplan-Meier and Proportional Hazards methods.


Information By: Roswell Park Cancer Institute

Dates:
Date Received: August 24, 2012
Date Started: October 5, 2012
Date Completion: February 5, 2019
Last Updated: March 7, 2017
Last Verified: March 2017