Extension Study to VEG105192 to Assess Pazopanib in Patients With Advanced/Metastatic Renal Cell Cancer

Study Overview
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Brief Summary
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This is an open-label, international, multi-center study designed to provide access to pazopanib for subjects who have been enrolled in the Phase III renal cell carcinoma study (VEG105192) and have progressed on placebo. Subjects will receive 800 mg pazopanib once daily. The study treatment will continue until subjects experience disease progression, unacceptable toxicity, withdrawal of consent, or death. The primary objective of the study is to evaluate the safety and tolerability of pazopanib for the treatment of renal cell carcinoma. The secondary objectives of the study are to assess response rate (defined as complete response or partial response), progression-free survival, and overall survival. Response rates will be collected per investigator assessment (no central review). Subjects will have a CT/MRI scan every 6 weeks until week 24 and every 12 weeks thereafter.

Official Title
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An Open-label Extension Study to Assess the Safety and Efficacy of Pazopanib in Subjects With Renal Cell Carcinoma Previously Enrolled on Protocol VEG105192

Conditions
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Carcinoma, Renal Cell

Intervention / Treatment
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* Drug: pazopanib


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Progressed from VEG105192 study treatment Patient's VEG105192 was placebo Baseline has good organ function Exclusion criteria: No brain metastasis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pazopanib arm<br>This was a single arm study, therefore no control arm. | Drug: pazopanib<br>* 800 mg daily dosing continously until progression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) | An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in other situations. | From Baseline to Follow-up (up to 6.230 years) | 
| Number of Participants With Any Adverse Event (Serious and Non-serious) of the Indicated Severity, Per National Cancer Institute (NCI) Common Terminology Criteria in Adverse Events (CTCAE) | An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in other situations. Adverse events were graded for severity according to the NCI CTCAE, version 3.0: Grade 1, mild; Grade 2, moderate; Grade 3 (G3), severe; Grade 4 (G4), life-threatening or disabling; Grade 5, death. | From Baseline to Follow-up (up to 6.230 years) | 
| Number of Participants With Adverse Events Related to Investigational Product | An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The investigator assessed relatedness between the AE and the investigational product. | From Baseline to Follow-up (up to 6.230 years) | 
| Median Time on Investigational Product | The time on investigational product (including dose interruptions) is defined as the difference between the date of the last dose of investigational product and the date of the first dose of investigational product plus one. | From Baseline to investigational product discontinuation (up to 6.230 years) | 
| Number of Participants With the Indicated Worst-case Toxicity Grade Increase From Baseline for the Indicated Clinical Chemistry Parameters at Any Time Post-Baseline | Clinical chemistry parameters were summarized according to NCI CTCAE, version 4.0: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening or disabling; Grade 5, death. Data are presented for only those parameters for which an increase from Baseline occurred. Clinical chemistry parameters included: alkaline phosphatase (ALP), alanine amino transferase (ALT), aspartate amino transferase (AST), total bilirubin (TB), calcium (hypercalcemia and hypocalcemia), creatinine, glucose (hyperglycemia and hypoglycemia), potassium (hyperkalemia and hypokalemia), magnesium (hypermagnesemia and hypomagnesemia), sodium (hypernatremia and hyponatremia), and phosphate. | From Baseline to investigational product discontinuation (up to 6.230 years) | 
| Number of Participants With the Indicated Worst-case Grade Increase From Baseline for the Indicated Hematology Parameters at Any Time Post-Baseline | Hematology parameters were summarized according to NIH CTCAE, version 4.0. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening or disabling; Grade 5, death. Data are presented for only those parameters for which an increase from Baseline occurred. Hematology parameters included: hemoglobin (anemia), lymphocytes (lymphocytopenia), neutrophils (neutropenia), platelets (thrombocytopenia), white blood cells (WBC [leukopenia]), and prothrombin time international normalized ratio (PT [INR]). Participants with missing Baseline grades are assumed to have a Baseline grade of 0. | From Baseline to investigational product discontinuation (up to 6.230 years) | 
| Number of Participants With the Indicated Shift From Baseline in Blood Pressure at Any Time Post-Baseline | Blood pressure measurements included systolic blood pressure (SBP, millimeters of mercury [mmHg]) and diastolic BP (DBP). The number of participants with a post-Baseline shift from Baseline in blood pressure (<90 mmHg, 90 to 139 mmHg, 140 to 169 mmHg, >=170 mmHg) was assessed. | From Baseline to investigational product discontinuation (up to 6.230 years) | 
| Number of Participants With the Indicated Shift in Heart Rate From Baseline at Any Time Post-Baseline | Heart rate is the measure of heart beats per minute (bpm). The number of participants with a post-Baseline shift from Baseline in heart rate of <44 bpm, 44 to 100 bpm, 101 to 120 bpm, and >120 bpm was assessed. | From Baseline to investigational product discontinuation (up to 6.230 years) | 
| Number of Participants With a Change From Baseline to the Indicated Worst-case Post-Baseline Bazett's Heart Rate-corrected QT Interval (QTc) Value | The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. A lengthened QT interval can be a biomarker for ventricular tachyarrhythmias. The QT interval corrected for heart rate using Bazett's formula (QTcB) was calculated; the faster the heart rate, the shorter the QT interval. Electrocardiogram values (Bazett's QTc value) were summarized using the following reference ranges: <450, 450 to 479, 480 to 499, 500 to 549, and >550 milliseconds. | From Baseline to investigational product discontinuation (up to 6.230 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Complete Response (CR) or Partial Response (PR) | Overall tumor response is defined as the number of participants achieving either a confirmed complete or partial tumor response per Response Evaluation Criteria in Solid Tumors (RECIST). RECIST guidelines were used to evaluate the measurability of tumor lesions, to determine target and non-target lesions at Baseline, and to evaluate tumor response or disease progression after study start. CR is defined as the disappearance of all target and non-target lesions, and PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions, taking as a reference the Baseline sum LD, as assessed by the investigator. Confirmation of a CR/PR required a subsequent assessment of the same response or better at least 28 days after the original response. | From Baseline to Week 24/investigational product discontinuation (up to 3.460 years) | 
| Number of Participants With a Response of Confirmed CR+PR+6-month Stable Disease (SD) | The number of participants who achieved either a CR, a PR, or a best response of SD that occurred at least 6 months after screening per RECIST criteria was assessed. CR is defined as the disappearance of all target and non-target lesions; PR is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD; and SD is defined as neither sufficient shrinkage in target lesions to qualify for PR, nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started and the persistence of one or more non-target lesion(s), as assessed by the investigator. Confirmation of a CR/PR required a subsequent assessment of the same response or better at least 28 days after the original response. A confirmed response of SD required that the SD assessment occurred no earlier than 12 weeks after the screening scans. | From the Baseline to Week 24/investigational product discontinuation (up to 1.65 years) | 
| Number of Participants With the Indicated Best Overall Response | The best overall response is defined as the best response recorded from the start of the treatment until disease progression (PD)/recurrence. Per RECIST: CR, the disappearance of all target and non-target lesions; PR, at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD; SD, neither sufficient shrinkage in target lesions to qualify for PR, nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started and the persistence of one or more non-target lesion(s); PD, at least a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum of the LD recorded since the treatment started or the appearance of >=1 new lesion and/or unequivocal progression of existing non-target lesions. Unknown/not evaluable is used for those participants who cannot be classified as achieving CR, PR, SD, or PD. | From the Baseline to Week 24/investigational product discontinuation (up to 3.460 years) | 
| Progression-free Survival (PFS) | PFS is defined as the interval between the date of the first dose of study medication and the date of disease progression as defined by the investigator or death due to any cause. RECIST was used to evaluate the measurability of tumor lesions, to determine target and non-target lesions at Baseline, and to evaluate tumor response or disease progression after study start. Per RECIST, PD is defined as at least a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum of the LD recorded since the treatment started or the appearance of >=1 new lesion and/or unequivocal progression of existing non-target lesions. Participants who did not have disease progression or did not die were censored at the follow-up visit as either follow-up ended or follow-up ongoing. Participants who received non-study anti-cancer therapies before disease progression were treated as censored. | From the first dose of study medication to the earliest date of disease progression (PD) or death due to any cause (up to 3.460 years) | 
| Overall Survival (OS) | OS is defined as the interval between the date of the first dose of study medication to the date of death due to any cause. For participants who did not die, time to death was censored at the time of last contact. The last date of contact was defined as the maximum date of any visit date or the survival follow-up date. | From the first dose of study medication to the earliest date of disease progression (PD) or death due to any cause (up to 3.460 years) | 
| Percentage of Participants Who Survived Until Month 12 | For participants who did not die, time to death was censored at the time of last contact. The last date of contact was defined as the maximum date of any visit date or the survival follow-up date. | From the first dose of study medication to Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal cell carcinoma, pazopanib, anti-angiogenic therapy, open label