Neoadjuvant Pazopanib in Renal Cell Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by UNC Lineberger Comprehensive Cancer Center
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01361113
First received: May 23, 2011
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

This study will be a single arm phase II clinical trial of 8 weeks of daily, oral neo-adjuvant pazopanib prior to nephrectomy in 39 evaluable patients with histologically confirmed localized renal cell carcinoma (RCC).


Condition Intervention Phase
Renal Cell Carcinoma
Drug: Pazopanib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Neoadjuvant Pazopanib: A Phase II Study to Evaluate the Effect on Disease Response and Recurrence and to Establish Predictive Biomarkers of Drug Activity in Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Response rate [ Time Frame: 8 weeks after neoadjuvant treatment ] [ Designated as safety issue: No ]
    Determine the objective response rate (CR+PR) using RECIST 1.1 at 8 weeks after neoadjuvant treatment with pazopanib in patients with locally advanced renal cell carcinoma


Secondary Outcome Measures:
  • Recurrence Free Survival (RFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Estimate recurrence free survival (RFS) following neoadjuvant treatment with pazopanib followed by nephrectomy, specifically reporting the 1 year and 2 year rate estimates with their 95% confidence intervals.

  • Altered surgical approach after treatment with pazopanib [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
    Determine if neoadjuvant treatment with pazopanib alters the planned surgical approach of the urologist, per documented radiographic (CT) response.

  • Number of participants with adverse events [ Time Frame: 14 weeks ] [ Designated as safety issue: Yes ]
    Identify any safety issues in subjects treated with pazopanib, neoadjuvantly, followed by nephrectomy.

  • Predictive molecular markers in response to treatment with pazopanib [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To assess the correlation between the expression of biomarkers and CT scan response. Patients are considered as responders when objective response (partial or complete response) is shown on CT scan and measured by RECIST version 1.1

  • Exploratory Analysis of Objective Response and Recurrence Free Survival rates [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To preform and exploratory analysis of the objective response rate (OR) and recurrence free survival (RFS) rates in the evaluable group who receives 4-7 weeks of therapy separately from the evaluable group who receives 8 weeks of therapy.


Estimated Enrollment: 56
Study Start Date: May 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Single Arm
Single arm trial
Drug: Pazopanib
800 mg orally once daily for 8 weeks, prior to nephrectomy
Other Name: Votrient

Detailed Description:

The primary objective of this study is to determine the objective response rate Complete Response + Partial Response(CR+PR) associated with neoadjuvant pazopanib at 8 weeks as defined via RECIST1.1. The investigators will also estimate the recurrence free survival (RFS), specifically the 1 and 2 year rates, with recurrence defined via RECIST1.1, and characterize the safety issues. Finally, this study also includes a number of exploratory analyses designed to evaluate potential correlations between RFS and; serum levels of cytokine and angiogenesis factor (CAF).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years with radiographic evidence of nonmetastatic renal cell carcinoma
  • Histological verification of clear cell renal cell carcinoma (-Clinical stage 2 (7 cm) or greater with localized disease
  • No evidence of extranodal metastatic disease
  • Appropriate candidate for surgery
  • ECOG Performance status of 0-1
  • Adequate organ function
  • Serum calcium, magnesium, potassium within normal limits
  • No known coagulopathy
  • Ability to read and follow instructions
  • Women of childbearing potential must have a negative serum pregnancy test performed within 14 days prior to the start of pazopanib treatment and both men and women must be willing to use adequate contraception.
  • Able to provide written, informed consent
  • Blood and urine samples must be provided from all subjects for biomarker analysis before and during treatment with pazopanib

Exclusion Criteria

  • Known or suspected allergy to pazopanib
  • Inability to swallow or retain oral medication
  • Prior malignancy Exception: Subjects who have had another malignancy and have been disease-free for three years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
  • Unable or unwilling to discontinue use of prohibited medications at least 7 days prior to the first dose of study drug and for the duration of the study.
  • Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including
  • History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
  • History of any one or more cardiovascular conditions within the past 6 months
  • Hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg OR diastolic blood pressure (DBP) of ≥ 90mmHg in spite of optimal medical management.
  • Evidence of active bleeding or bleeding diathesis.
  • Any serious and/or unstable pre-existing medical (especially hepatic disease), psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
  • Prior major surgery or trauma within 28 days prior to first dose of pazopanib and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major).
  • Pregnant or breastfeeding; breastfeeding may not resume for 14 days after the last dose of pazopanib
  • Prior treatment with any of the following anti-cancer therapies for treatment of their RCC:

    • radiation therapy, surgery or tumor embolization
    • chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy
  • Baseline QTc>480 msec or other clinically significant baseline ECG abnormality
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01361113

Contacts
Contact: Gayle Grigson, RN (919) 966-4432 gayle_grigson@med.unc.edu
Contact: Donna Rowe, RN (919) 966-7359 donna_rowe@med.unc.edu

Locations
United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
Principal Investigator: Himisha Beltran, MD         
United States, North Carolina
North Carolina Cancer Hospital (UNC) Recruiting
Chapel Hill, North Carolina, United States, 27599
Carolinas HealthCare System Withdrawn
Charlotte, North Carolina, United States, 28262
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Principal Investigator: Edward Rampersaud, MD         
United States, South Carolina
Medical University of South Carolina (MUSC) Withdrawn
Charleston, South Carolina, United States, 29425
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Christopher Wood, MD         
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
GlaxoSmithKline
Investigators
Principal Investigator: Kimryn Rathmell, MD UNC Lineberger Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01361113     History of Changes
Other Study ID Numbers: LCCC 1028, 11-0457
Study First Received: May 23, 2011
Last Updated: April 24, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
Renal Cell Carcinoma
RCC
Votrient
Pazopanib
Nephrectomy
Neoadjuvant
Phase II
LCCC 1028
Lineberger Comprehensive Cancer Center

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on July 20, 2014