Clinical Trial VICCURO1088
A Randomized, Double-Blind, Placebo-Controlled Phase III Study to Evaluate the Efficacy and Safety of Pazopanib as Adjuvant Therapy for Subjects with Localized or Locally Advanced RCC Following Nephrectomy
- Protocol No. VICCURO1088
- Open Date: 08/15/2011
- Staging: Phase III
- Age Group: Adults
- Scope: National
- Objective: To evaluate disease-free survival (DFS) with pazopanib as compared to placebo as adjuvant therapy for subjects with localized/locally advanced RCC following nephrectomy.
- Disease Sites: Kidney (Renal Cell)
- Therapies: Molecular Targeted Agents / Immunotherapy / Biologics
- Drugs: Blinded Drug; Pazopanib
- Participating Institutions: Vanderbilt University
- National Clinical Trial ID: NCT01235962
- Secondary Protocol No: VEG113387
Patients are asked to take part in this research study because they have been diagnosed with a renal cell tumor, a type of kidney cancer, and have had surgery to remove the tumor from their kidney. Patients may have had part or all of a kidney removed. Even though all of the visible tumor may have been taken out, very small tumor cells can remain in the body. They can grow and build a new tumor somewhere in the body months or even years later. If and how soon the tumor may come back depends on many factors. Some factors we know and some we don-t know. The study doctor will be able to discuss the risks of the tumor coming back if patients do not have any additional treatment after their kidney tumor was removed. The purpose of this study is to test if the drug pazopanib (also called Votrient) can prevent or delay the renal cell tumor from coming back after the tumor has been surgically removed. The study will also test the safety of pazopanib. As of September 2010, about 5000 patients with various cancers have been enrolled in pazopanib studies. As of November 2010, pazopanib has been approved by regulatory agencies in the US, Europe and other countries for treating patients whose renal cell cancer has spread to other parts of the body. The use of pazopanib in this study is new. Pazopanib has not yet been approved by the Food and Drug Administration (FDA) for doctors to prescribe to patients to prevent or delay their tumor coming back after it has been surgically removed. It has to be tested first. About 1500 adult people in about 25 countries in North America, South America, Asia and Europe will take part in this study. Once we have about 1500 people who agree to take part in the study and meet the eligibility criteria we will not invite any more. About 20 people will take part in this study at Vanderbilt. How does the study work- This study will compare pazopanib and a placebo. Placebo is a type of pill that is made to look the same as a pazopanib pill however, it contains no active drug. One group of people will take pazopanib and another group will take the placebo. The effects of pazopanib, both good and bad, will be compared with the effects of the placebo. The reason that placebo is selected to compare with pazopanib is because no drug has been approved to prevent or delay renal cell tumor from coming back after it is surgically removed. A computer will put people into the two groups by chance. Patients have an equal (or 50%) chance of being placed in either group. Neither the patient nor the study doctor can choose a group. During the study, neither the patient nor the study doctor will know which group the patient is in. This way, the findings from the two groups will be handled in the same way. Patients will be told which group they are in only in case of a medical emergency or if the tumor returns. Information about how the study drug patients get affects them body and their health will be collected through a number of tests and procedures.
|Ages Eligible for Study:||18 Years and older|
|Genders Eligible for Study:||Both|
|Accepts Healthy Volunteers:||No|
• Signed written informed consent
• Diagnosis of RCC with clear-cell or predominant clear-cell histology
• Subjects with non-metastatic disease (M0) fulfilling any of the following combinations of pathologic staging based on American Joint Committee on Cancer (AJCC) TNM staging version 2010 and Fuhrman nuclear grading.
• pT2, G3 or G4, N0; or,
• pT3, G any, N0; or,
• pT4, G any, N0; or,
• pT any, G any, N1
• Fulfill all of the following criteria of disease-free status at baseline:
• Had complete gross surgical resection of all RCC via radical or partial nephrectomy using either open or laparoscopic technique.
• Baseline imaging of chest, abdomen and pelvis shows no metastasis or residual tumor lesions as confirmed centrally by an independent radiologist.
• Received no prior adjuvant or neo-adjuvant treatment for RCC
• Recovered from nephrectomy: any surgery related toxicities should be reduced to ≤ grade 1 per NCI Common Terminology Criteria for Adverse Events (CTCAE) (Version 4)
• Karnofsky performance scale (KPS) of ≥ 80
• Adequate organ system function
• 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
• 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
• Active diarrhea of any grade
• 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
• History of human immunodeficiency virus (HIV) infection
• History of active hepatitis
• Presence of uncontrolled infection.
• 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 vascular disease
• History of Class III or IV congestive heart failure, as defined by the New York Heart Association Classification of Congestive Heart Failure
• History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
• Corrected QT interval (QTc) > 480 milliseconds (msec)
• Poorly controlled hypertension, defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg.
Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Blood pressure (BP) must be re-assessed on two occasions that are separated by a minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP / DBP values from each BP assessment 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).
• Evidence of active bleeding or bleeding diathesis
• Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
• Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study treatment and for the duration of the study.
• Concurrent therapy given to treat cancer including treatment with an investigational agent or concurrent participation in another clinical trial involving anti-cancer investigational drug.
• Administration of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study treatment.
• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or excipients that in the opinion of the investigator contraindicates their participation.
• Prior or current use of systemic anti-VEGF inhibitors, cytokines (e.g. interferon, interleukin 2).