Neoadjuvant Pazopanib in Renal Cell Carcinoma
Primary Purpose
Renal Cell Carcinoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pazopanib
Sponsored by
About this trial
This is an interventional treatment trial for Renal Cell Carcinoma focused on measuring Renal Cell Carcinoma, RCC, Votrient, Pazopanib, Nephrectomy, Neoadjuvant, Phase II, LCCC 1028, Lineberger Comprehensive Cancer Center
Eligibility 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
- 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
Sites / Locations
- North Carolina Cancer Hospital (UNC)
- MD Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Single Arm Neoadjuvant Pazopanib
Arm Description
Pazopanib 800 mg PO once daily for 8 weeks
Outcomes
Primary Outcome Measures
Response Rate
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.
Secondary Outcome Measures
Recurrence Free Survival (RFS)
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.
Number of Participants Who Needed an Altered Surgical Approach After Treatment With Pazopanib
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 Related to Treatment.
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.
Full Information
NCT ID
NCT01361113
First Posted
May 23, 2011
Last Updated
March 27, 2018
Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
GlaxoSmithKline
1. Study Identification
Unique Protocol Identification Number
NCT01361113
Brief Title
Neoadjuvant Pazopanib in Renal Cell Carcinoma
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
June 2011 (undefined)
Primary Completion Date
January 7, 2015 (Actual)
Study Completion Date
February 15, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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).
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Cell Carcinoma
Keywords
Renal Cell Carcinoma, RCC, Votrient, Pazopanib, Nephrectomy, Neoadjuvant, Phase II, LCCC 1028, Lineberger Comprehensive Cancer Center
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single Arm Neoadjuvant Pazopanib
Arm Type
Other
Arm Description
Pazopanib 800 mg PO once daily for 8 weeks
Intervention Type
Drug
Intervention Name(s)
Pazopanib
Other Intervention Name(s)
Votrient
Intervention Description
800 mg orally once daily for 8 weeks, prior to nephrectomy
Primary Outcome Measure Information:
Title
Response Rate
Description
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.
Time Frame
8 weeks after neoadjuvant treatment
Secondary Outcome Measure Information:
Title
Recurrence Free Survival (RFS)
Description
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.
Time Frame
2 years
Title
Number of Participants Who Needed an Altered Surgical Approach After Treatment With Pazopanib
Description
Determine if neoadjuvant treatment with pazopanib alters the planned surgical approach of the urologist, per documented radiographic (CT) response.
Time Frame
14 weeks
Title
Number of Participants With Adverse Events Related to Treatment.
Description
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.
Time Frame
9 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William Kim, MD
Organizational Affiliation
UNC Lineberger Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
North Carolina Cancer Hospital (UNC)
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Links:
URL
http://cancer.med.unc.edu/
Description
Lineberger Comprehensive Cancer Center
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Neoadjuvant Pazopanib in Renal Cell Carcinoma
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