Neoadjuvant Pazopanib in Renal Cell Carcinoma

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

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).

Study Overview

Status

Completed

Intervention / Treatment

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 Response Evaluation Criteria in Solid Tumors (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).

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • North Carolina Cancer Hospital (UNC)
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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
  • The Eastern Cooperative Oncology Group (ECOG) Performance status of 0-1
  • Adequate organ function
  • Serum calcium, magnesium, potassium within normal limits, or if outside of normal limits, must be deemed clinically insignificant by the Investigator.
  • 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 ≥ 90 mmHg 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 Corrected QT Interval (QTc) >480 msec or other clinically significant baseline ECG abnormality

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Single Arm Neoadjuvant Pazopanib
Pazopanib 800 mg PO once daily for 8 weeks
800 mg orally once daily for 8 weeks, prior to nephrectomy
Other Names:
  • Votrient

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Rate
Time Frame: 8 weeks after neoadjuvant treatment

Determine the objective response rate (CR+PR) using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 at 8 weeks after neoadjuvant treatment with pazopanib in patients with locally advanced renal cell carcinoma.

Evaluation of Target Lesions using RECIST 1.1 Criteria:

Complete response (CR)-Disappearance of all target lesions. Any pathological lymph node (LN) target or no must have decreased in short axis to <10mm.

Partial response (PR)-At least a 30% decrease in the sum of the longest diameter (LD) of the target lesions taking as reference the baseline sum LD.

8 weeks after neoadjuvant treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recurrence Free Survival (RFS)
Time Frame: 2 years
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.
2 years
Number of Participants Who Needed an Altered Surgical Approach After Treatment With Pazopanib
Time Frame: 14 weeks
Determine if neoadjuvant treatment with pazopanib alters the planned surgical approach of the urologist, per documented radiographic (CT) response.
14 weeks
Number of Participants With Adverse Events Related to Treatment.
Time Frame: 9 weeks

Identify any safety issues in subjects treated with pazopanib, neoadjuvantly, followed by nephrectomy. Number of patients that had adverse events reported that had an attribution of; possible, probable, or definite that are graded a 3 or higher according to Common Terminology Criteria for Adverse Events (CTCAE v4.0).

Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.

Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental activities of daily living Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living.

Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to adverse event.

9 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: William Kim, MD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2011

Primary Completion (Actual)

January 7, 2015

Study Completion (Actual)

February 15, 2017

Study Registration Dates

First Submitted

May 23, 2011

First Submitted That Met QC Criteria

May 25, 2011

First Posted (Estimate)

May 26, 2011

Study Record Updates

Last Update Posted (Actual)

April 25, 2018

Last Update Submitted That Met QC Criteria

March 27, 2018

Last Verified

March 1, 2018

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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