A study to test whether pazopanib can prevent or delay kidney tumor coming back after the tumor has been removed

Phase 1

Conditions: Renal Cell Carcinoma
MedDRA version: 20.0 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: 20.0 Level: PT Classification code 10067946 Term: Renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2010-020965-26-IE

Lead Sponsor: ovartis Pharma Services AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 1500

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

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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Related Trials