A Study to Evaluate Pazopanib as an Adjuvant Treatment for Localized Renal Cell Carcinoma (RCC) (PROTECT)
This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
First received: October 14, 2010
Last updated: January 16, 2014
Last verified: January 2014
This randomized Phase III study is to evaluate whether pazopanib compared with placebo can prevent or delay recurrence of kidney cancer in patients with moderately high or high risk of developing recurrence after undergoing kidney cancer surgery
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
||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
Primary Outcome Measures:
- Disease-free survival [ Time Frame: approximately 6 years ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Overall survival [ Time Frame: approximately 9 years ] [ Designated as safety issue: No ]
- Disease-free survival rates at yearly time points (e.g. 1 year, 2 years, etc.). [ Time Frame: yearly for 4 or 5 years ] [ Designated as safety issue: No ]
- Safety (frequency and severity of adverse events and laboratory abnormalities) [ Time Frame: approximately 12 months ] [ Designated as safety issue: Yes ]
- Health Outcome (change from baseline in patients' self-reports on health outcome and quality of life as measured by two instruments: Cancer Therapy-Kidney Symptom Index-19 and EuroQOL-5D [ Time Frame: approximately 6 years ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||October 2016 (Final data collection date for primary outcome measure)
Pazopanib oral agent, administered at 600 mg daily initial dose for 8-12 weeks. Dose can be escalated to 800 mg daily based on safety evaluation. Complete treatment is 12 months. Dose can be reduced, interrupted or discontinued due to adverse events or intolerance.
Pazopanib 600 mg daily initial dose for 8-12 weeks, dose can be escalated to 800 mg daily based on safety evaluation.
Other Name: Votrient
Placebo Comparator: placebo
placebo matching pazopanib 200 mg tablets, administered at 600 mg daily initial dose for 8-12 weeks. Dose can be escalated to 800 mg daily based on safety evaluation. Complete treatment is 12 months. Dose can be reduced, interrupted or discontinued due to adverse events or intolerance.
placebo matching pazopanib daily initial dose for 8-12 weeks, dose can be escalated to 800 mg daily based on safety evaluation.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01235962
||GSK Clinical Trials
Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarbá JJ, Chen M, McCann L, Pandite L, Roychowdhury DF, Hawkins RE. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010 Feb 20;28(6):1061-8. doi: 10.1200/JCO.2009.23.9764. Epub 2010 Jan 25.
History of Changes
|Other Study ID Numbers:
|Study First Received:
||October 14, 2010
||January 16, 2014
||Canada: Health Products and Foods Branch, Health Canada
Spain: Agencia Espanola de Medicamentos y Productos Sanitarios
Slovakia: State Institute for Drug Control
Argentina: Ministry of Health - A.N.M.A.T
Belgium: Agence Fédérale des Médicaments et des Produits de la Santé
Brazil: National Health Surveillance Agency
Italy: Agenzia Italiana del Farmaco
Chile:Ministerio de Salud de Chile
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Ireland: Irish Medicines Board
United States: Food and Drug Administration
Austria: Austrian Medicines and Medical Devices Agency (AGES PharmMed)
South Korea: Korea Food and Drug Administration (KFDA)
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
Denmark: Danish Medicines Agency
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Russia: Ministry of Health of the Russian Federation
Japan: Pharmaceuticals and Medical Devices Agency
Israel: Ministry of Health
China: Food and Drug Administration
Europe: European Medicines Agency
Turkey: Ministry of Health
Czech Republic: State Institute for Drug Control
Keywords provided by GlaxoSmithKline:
renal cell carcinoma
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on April 23, 2014
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site