Renal Cell Carcinoma MedDRA version: 19.0 Level: LLT Classification code 10038415 Term: Renal cell carcinoma stage unspecified System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 19.0 Level: PT Classification code 10067946 Term: Renal cell carcinoma System Organ Class: 1002
Conditions
Interventions
Trade Name: Votrient
Product Name: Votrient (GW786034)
Product Code: Votrient (GW786034)
Pharmaceutical Form: Film-coated tablet
INN or
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent 2. Diagnosis of RCC with clear-cell or predominant clear-cell histology. 3. Subjects with non-metastatic disease (M0) fulfilling any of the following combinations of pathologic staging based on AJCC TNM staging version 2010 and Fuhrman nuclear grading [see Section 12.2 Appendix 2 and Section 12.3 Appendix 3 for details]. • pT2, G3 or G4, N0; or, • pT3, Gany, N0; or, • pT4, Gany, N0; or, • pTany, Gany, N1 Note 1: Excisional biopsy is required of all regional lymph node(s) which appear abnormal on pre-operative scans or at surgery. In order to properly stratify subjects (see Section 5.5), it is required that the investigator designate the nodal status as either N0 or N1 according to the following criteria which will be captured in the eCRF: N0 requires that a subject have no abnormal regional lymph nodes on preoperative scans or visualized at surgery, OR have regional lymph nodes biopsied with negative (no tumor present) result. N1 requires that a subject have regional lymph nodes biopsied with positive (tumor present) result. Note 2: Subjects with ipsilateral multicentric RCC are eligible if the most advanced lesion per pT stage fulfils any of the aforementioned combinations of pathologic staging and Fuhrman nuclear grading. 4. Fulfill all of the following criteria of disease-free status at baseline: • Had complete gross surgical resection of all RCC via nephrectomy. • Baseline imaging of chest, abdomen and pelvis shows no metastasis or residual tumor lesions as confirmed centrally by an independent radiologist. Note: As noted above, excisional biopsy is required of all regional lymph node(s) which appear abnormal on pre-operative scans or at surgery. In event lymphadenectomy was not performed during surgery, subjects with one or more regional lymph nodes identified with short axis of =15mm by Independent Central Imaging Review of the baseline scans are considered to have gross residual disease and therefore ineligible. See Section 7.5.3 for Guideline of Imaging Diagnosis for Baseline Disease-free Status. 5. Received no prior adjuvant or neo-adjuvant treatment for RCC. 6. Recovered from nephrectomy: any surgery related toxicities should be reduced to = grade 1 per NCI CTCAE (Version 4) 7. Karnofsky performance scale (KPS) of = 80. 8. Adequate organ system function as defined in Table 3, page 26 of Protocol 02 9. Male or female, age = 18 years Note 1: Female subjects of childbearing potential must have a negative serum or unrine pregnancy test within 7 days of the first dose of study treatment and agree to use an effective contraception method, as described in Section 7.6.7.1, during Study Treatment Period until 14 days following the last dose of study treatment. Refer to Section 7.6.7.1 for the definitions of female of childbearing potential and female of non-childbearing potential. Note 2: Female subjects who are lactating must discontinue nursing prior to the first dose of study treatment and refrain from nursing throughout the study treatment period
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Locally recurrent RCC, bilateral RCC, or history of another malignancy Exception: Subjects who have had another malignancy and have been disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible. 2. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: • Active peptic ulcer disease • Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment 3. Active diarrhea of any grade 4. Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: • Malabsorption syndrome • Major resection of the stomach or small bowel resulting in dumping syndrome or clinical signs of malabsorption 5. History of human immunodeficiency virus (HIV) infection. 6. History of chronic active hepatitis including subjects who are carriers of hepatitis B virus (HBV) or hepatitis C virus (HCV) 7. Presence of uncontrolled infection. 8. History of any one or more of the following cardiovascular conditions within the past 6 months: • Cardiac angioplasty or stenting • Myocardial infarction • Unstable angina • Coronary artery bypass graft surgery • Symptomatic peripheral arterial vascular disease 9. History of Class III or IV congestive heart failure, as defined by the New York Heart Association Classification of Congestive Heart Failure [See Section 12.7 Appendix 7 for description] 10. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anticoagulating agents for at least 6 weeks are eligible 11. Corrected QT interval (QTc) > 480 milliseconds (msec) 12. Poorly controlled hypertension, defined as systolic blood pressure (SBP) of =140 mmHg or diastolic blood pressure (DBP) of = 90mmHg. Note: Screening/Baseline blood pressure (BP) must be assessed with three measurements at approximately 2-minute intervals. The mean SBP / DBP values from the three readings must be <140/90 mmHg in order for a subject to be eligible for the study (see Section 7.6.2 for instruction on blood pressure measurement and obtaining mean blood pressure values). If the subject’s initial screening SBP/DBP is = 140/90mmHg, initiation or adjustment of antihypertensive medication(s) is permitted in an attempt to control the subject’s BP level to below 140/90mmHg. Once the subject’s BP level is wellcontrolled, BP must be re-assessed with three measurements at approximately 2- minute intervals and the mean SBP/DBP fr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate disease-free survival (DFS) with pazopanib 600 mg daily initial dose as compared to placebo as adjuvant therapy for subjects with localized/locally advanced RCC following nephrectomy.; Secondary Objective: Efficacy objectives: •To evaluate OS and DFS rates at yearly time points (e.g.1 year, 2 years,etc)with pazopanib 600 mg daily initial dose compared to placebo. •To evaluate efficacy endpoints: DFS,OS and DFS rates at yearly time points,with pazopanib compared to placebo as adjuvant RCC treatment in all subjects(regardless of whether 600 mg or 800 mg daily initial dose is used). •To evaluate efficacy endpoints DFS and OS with pazopanib 800 mg daily initial dose compared to placebo. Safety objective: •To evaluate safety and tolerability in subjects treated with pazopanib 600 mg daily initial dose compare to those treated with placebo. •To evaluate safety and tolerability in subjects treated with pazopanib compared to those treated with placebo in all subjects (regardless of whether 600mg or 800 mg daily initial dose is used). •To summarize selected safety and tolerability parameters in subjects treated with pazopanib 800mg daily initial dose compared to those treated with placebo. ;Primary end point(s): The primary efficacy endpoint of this study is DFS, which is defined as time from randomization to developing local disease recurrence and/or metastasis, or death due to any cause whichever comes first;Timepoint(s) of evaluation of this end point: Imaging assessments are the major evaluations for DFS, which will be done at baseline, week 20, 36, 52, every 6 months between year 2-5, then yearly thereafter until study reached the clinical cutoff for DFS. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1) Overall survival, defined as the interval from randomization to death due to any cause; Secondary end point(s): • OS, defined as time from randomization to death due to any cause. • DFS rates at yearly time points (e.g. 1 year, 2 years, etc.). Actual time points will depend on data maturity at the time of the DFS analysis • The safety endpoints include the incidence, severity and causality of all AE, SAE and other safety parameters during treatment period. Long term safety will also be analyzed. • Change from baseline in subject self-reports on health outcome and quality of life as measured by Cancer Therapy-Kidney Symptom Index -19 (FKSI-19) and EuroQOL (EQ-5D), respectively. | — |
Countries
Austria, Belgium, Czech Republic, Denmark, Germany, Greece, Hungary, Ireland, Italy, Poland, Slovakia, Spain, United Kingdom
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma Services AG
Outcome results
None listed