Safety and Efficacy of GW786034 (Pazopanib) In Metastatic Renal Cell Carcinoma

NCT00334282 | Completed Phase 3 Results DMC

• 1 other identifier: VEG105192
• Study Type: interventional
• Target: 435
• Locations: 24 countries
• Sites: 94

Brief Summary

To evaluate efficacy and safety of pazopanib compared to placebo in patients with locally advanced and/ or metastatic renal cell carcinoma (RCC). Approximately 350-400 eligible patients will be stratified and randomized in a 2:1 ratio to receive either 800 mg pazopanib once daily or matching placebo. The study treatment will continue until patients experience disease progression, unacceptable toxicity or death. Primary objective of the study is to evaluate and compare the two treatment arms for progression-free survival. Principal secondary objective is to evaluate and compare the two treatment arms with respect to overall survival. Other objectives are overall response rate \[complete response (CR) + partial response (PR)\], rate of CR + PR + 6 months stable disease, and the incidence, severity and causality of adverse events and serious adverse events. Safety and efficacy assessments will be regularly performed on all patients. An Independent Data Monitoring Committee will be established to monitor safety during the course of the study and to evaluate interim efficacy data on overall survival.

Conditions

Carcinoma, Renal Cell

Keywords

Metastatic; Anti-angiogenesis; GW786034; Pazopanib

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Progression-free survival (PFS) is defined as the interval between the date of randomization and the earliest date of disease progression or death due to any cause. Assessments of progression and non-progression were made by an independent imaging review committee (IRC) for the primary analysis.

  Randomization until progression (up to 2 years)

Secondary Outcomes (10)

• Overall Survival

  Randomization until death (up to 2 years)

• Overall Response

  Baseline until either response or progression (up to 2 years)

• Participants With Complete Response, Partial Response, or 6 Months of Stable Disease

  Baseline until 6 months post-Baseline or progressive disease

• Duration of Response

  Time from response until progression (up to 2 years)

• Time to Response as Assessed by an Independent Review Committee (IRC) and the Investigator

  Randomization until CR or PR (assessed for up to 2 years)

Study Arms (2)

placebo arm

PLACEBO COMPARATOR

matching placebo (800 mg tablet) once daily

Drug: placebo

pazopanib arm

EXPERIMENTAL

Oral pazopanib tablet 800 mg once daily continuously

Drug: Pazopanib

Interventions

Pazopanib DRUG

Oral pazopanib tablet 800 mg once daily continuously

Also known as: votrient

pazopanib arm

placebo DRUG

matching placebo (800 mg tablet) once daily

placebo arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent.
• Diagnosis of clear cell RCC that is predominantly clear cell histology. Note: cytology cannot be the only pathologic criteria to confirm clear cell RCC. Patients with tumor types that are interpreted as non-clear cell, e.g. papillary, are excluded.
• Locally advanced RCC (defined as disease not amenable to curative surgery or radiation therapy) or metastatic RCC (equivalent to Stage IV RCC according to American Joint Committee on Cancer (AJCC) staging.
• Note: If the metastatic disease is restricted to a solitary lesion, its neoplastic nature must be confirmed by histology or cytology. Cytology cannot be the only pathologic criteria to confirm clear cell RCC, but can be used in a patient with histologically confirmed clear cell RCC to confirm that metastatic disease is neoplastic in nature.
• Must have measurable disease, i.e. presenting with at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST). A measurable lesion is defined as a lesion that can be accurately measured in at least one dimension with the longest diameter ≥ 20 mm using conventional techniques, or ≥ 10 mm with spiral CT scan.
• Note: Patient should be excluded if all baseline measurable lesions are within previously irradiated areas.
• Note: A patient must complete all the baseline disease assessments in order to be eligible. Baseline head, chest, abdominal and pelvic CT or MRI scans must be performed within 2 weeks prior to the first dose of study medication; baseline bone scan must be performed within 3 weeks of the first dose of study medication.
• Patients who have received only one prior systemic treatment for locally advanced or metastatic RCC with documented disease progression or documented treatment discontinuation due to unacceptable toxicity. This first-line systemic treatment must be cytokine based.
• Note: The first-line cytokine-based treatment can be interleukin-2 (IL-2) or interferon-α (INFα) monotherapy, IL-2 in combination with INF-α, IL-2 and/or INF-α in combination with chemotherapy, hormonal or other therapies excluding agents targeting angiogenesis pathways. Agents in a combination regimen can be given sequentially if the treatment sequence is pre-determined and the patient does not fail one agent prior to starting another.
• Note: Prior adjuvant or neo-adjuvant therapies are permitted excluding any agents that target vascular endothelial growth factor (VEGF) or VEGF receptors. The adjuvant/neo-adjuvant therapies should not be considered as first-line systemic treatment for advanced RCC.
• Or,
• Patients who have received no prior systemic therapy for advanced/metastatic RCC can be enrolled if under any of the following circumstances:
• Patients who live in countries or regions where there is no established standard first-line therapy for advanced/metastatic RCC or where there are barriers to the access of established therapies such as sunitinib, sorafenib, IFNα or IL-2.
• Patients who live in countries or regions where IL-2 or INF-α has been approved for the treatment of advanced/metastatic RCC, however, these agents are generally not recognized by the local clinical community as a standard treatment for advanced/metastatic RCC, or where the physician and the patient have determined that the available cytokine therapies are not an acceptable therapeutic option.
• Patients who have recurred following prior adjuvant or neo-adjuvant cytokine therapy for RCC are eligible to participate without receiving a first-line systemic treatment for locally advanced or metastatic RCC. These patients should be stratified as the first-line population.

You may not qualify if:

• Pregnant or lactating female.
• History of another malignancy.
• Note: Patients who have had another malignancy and have been disease-free for 5 years, or patients with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible.
• History or presence of central nervous system (CNS) metastasis or leptomeningeal tumors as documented by CT or MRI scan, analysis of cerebrospinal fluid or neurological exam.
• Note: A baseline brain CT or MRI scan must be obtained in all patients within 2 weeks of the first dose of study medication.
• Malabsorption syndrome or disease that significantly affects gastrointestinal function, or major resection of the stomach or small bowel that could affect the absorption of pazopanib.
• Unable to swallow and retain orally administered medication.
• Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to beginning study treatment.
• History of human immunodeficiency virus infection.
• Presence of uncontrolled infection.
• Corrected QT interval (QTc) prolongation defined as QTc interval \> 470 msecs.
• History of Class III or IV congestive heart failure according to New York Heart Association (NYHA) classification.
• History of any one of the following cardiac conditions within the past 6 months:
• Cardiac angioplasty or stenting, or
• Myocardial infarction, or

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (99)

GSK Investigational Site

Capital Federal, Buenos Aires, C1405CUB, Argentina

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GSK Investigational Site

Córdoba, Córdoba Province, 5000, Argentina

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Rosario, Santa Fe Province, S2000KZE, Argentina

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GSK Investigational Site

Quilmes, 1878, Argentina

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San Miguel de Tucumán, 4000, Argentina

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St Leonards, New South Wales, 2065, Australia

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Waratah, New South Wales, 2298, Australia

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Hobart, Tasmania, 7000, Australia

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Heidelberg, Victoria, 3084, Australia

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Wodonga, Victoria, 3690, Australia

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Salzburg, A-5020, Austria

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Vienna, 1130, Austria

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Vienna, A-1090, Austria

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Vienna, A-1100, Austria

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Belo Horizonte, Minas Gerais, 30150-270, Brazil

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Porto Alegre, Rio Grande do Sul, 90610 000, Brazil

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Jaú, São Paulo, 17210-120, Brazil

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Viña del Mar, Región de Valparaíso, 254-0364, Chile

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Santiago, Región Metro de Santiago, 7500921, Chile

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Santiago, Región Metro de Santiago, 7591046, Chile

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Beijing, 100034, China

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Beijing, 100853, China

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Brno, 656 53, Czechia

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Chomutov, 430 12, Czechia

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Ostrava - Poruba, 708 52, Czechia

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Prague, 12808, Czechia

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Tallinn, 11619, Estonia

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Tartu, 51014, Estonia

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Athens, 115 22, Greece

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Athens, 115 26, Greece

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Athens, 115 28, Greece

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Athens, 185 37, Greece

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Pátrai, 26500, Greece

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Thessaloniki, 564 29, Greece

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Hong Kong, Hong Kong

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Kowloon, Hong Kong

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Tuen Mun, New Territories, Hong Kong

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Bangalore, 560029, India

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Hyderabad, 500033, India

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Mumbai, 400026, India

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Pune, 411 004, India

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Trivandrum, 695011, India

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Galway, Ireland

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Tallaght, Dublin, 24, Ireland

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Rome, Lazio, 00133, Italy

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Rome, Lazio, 00152, Italy

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Casalpusterlengo (LO), Lombardy, 26841, Italy

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Crema, Lombardy, 26013, Italy

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Milan, Lombardy, 20132, Italy

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Rozzano (MI), Lombardy, 20089, Italy

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Orbassano (TO), Piedmont, 10043, Italy

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Riga, LV 1002, Latvia

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Kaunas, LT-50009, Lithuania

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Klaipėda, LT-92228, Lithuania

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Vilnius, LT-08660, Lithuania

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Guadalajara, Jalisco, CP44280, Mexico

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Mérida, Yucatán, 97500, Mexico

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Mexico City, CP 14080, Mexico

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Christchurch, 8001, New Zealand

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Newtown, Wellington, 6002, New Zealand

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Palmerston North, 4414, New Zealand

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Islamabad, 1590, Pakistan

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Karachi, 74800, Pakistan

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Lahore, 54600, Pakistan

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Gdansk, 80-210, Poland

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Krakow, 31-108, Poland

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Krakow, 31-115, Poland

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Olsztyn, 10-226, Poland

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Olsztyn, 10-228, Poland

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Poznan, 60-569, Poland

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Warsaw, 00-909, Poland

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Chelyabinsk, 454087, Russia

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Kazan', 420029, Russia

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Moscow, 115 478, Russia

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Moscow, 117 837, Russia

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Moscow, 129 128, Russia

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Omsk, 644013, Russia

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Saint Petersburg, 198255, Russia

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Samara, 443066, Russia

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Voronezh, 394062, Russia

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Yaroslavl, 150054, Russia

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Bratislava, 833 10, Slovakia

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Seoul, 110-744, South Korea

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Seoul, 120-752, South Korea

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GSK Investigational Site

Songpa-gu, Seoul, 138-736, South Korea

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GSK Investigational Site

Sfax, 3000, Tunisia

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Sousse, 4054, Tunisia

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Tunis, 1007, Tunisia

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Tunis, 1008, Tunisia

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Donetsk, 83092, Ukraine

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Kharkiv, 61037, Ukraine

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Kyiv, 03115, Ukraine

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Lviv, 79031, Ukraine

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GSK Investigational Site

Zaporizhzhya, 69600, Ukraine

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Exeter, Devon, EX2 5DW, United Kingdom

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Manchester, Lancashire, M20 4BX, United Kingdom

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Bebington, Wirral, CH63 4JY, United Kingdom

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GSK Investigational Site

Belfast, BT9 7AB, United Kingdom

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GSK Investigational Site

Swansea, SA2 8QA, United Kingdom

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Related Publications (11)

• Bonate PL, Suttle AB. Modeling tumor growth kinetics after treatment with pazopanib or placebo in patients with renal cell carcinoma. Cancer Chemother Pharmacol. 2013 Jul;72(1):231-40. doi: 10.1007/s00280-013-2191-0. Epub 2013 May 29.

  PMID: 23715625 BACKGROUND

• Tran HT, Liu Y, Zurita AJ, Lin Y, Baker-Neblett KL, Martin AM, Figlin RA, Hutson TE, Sternberg CN, Amado RG, Pandite LN, Heymach JV. Prognostic or predictive plasma cytokines and angiogenic factors for patients treated with pazopanib for metastatic renal-cell cancer: a retrospective analysis of phase 2 and phase 3 trials. Lancet Oncol. 2012 Aug;13(8):827-37. doi: 10.1016/S1470-2045(12)70241-3. Epub 2012 Jul 2.

  PMID: 22759480 BACKGROUND

• Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, Barrios CH, Salman P, Gladkov OA, Kavina A, Zarba 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.

  PMID: 20100962 BACKGROUND

• Maitland ML, Wu K, Sharma MR, Jin Y, Kang SP, Stadler WM, Karrison TG, Ratain MJ, Bies RR. Estimation of renal cell carcinoma treatment effects from disease progression modeling. Clin Pharmacol Ther. 2013 Apr;93(4):345-51. doi: 10.1038/clpt.2012.263. Epub 2012 Dec 27.

  PMID: 23443753 BACKGROUND

• Xu CF, Reck BH, Goodman VL, Xue Z, Huang L, Barnes MR, Koshy B, Spraggs CF, Mooser VE, Cardon LR, Pandite LN. Association of the hemochromatosis gene with pazopanib-induced transaminase elevation in renal cell carcinoma. J Hepatol. 2011 Jun;54(6):1237-43. doi: 10.1016/j.jhep.2010.09.028. Epub 2011 Feb 12.

  PMID: 21145803 BACKGROUND

• Xu CF, Reck BH, Xue Z, Huang L, Baker KL, Chen M, Chen EP, Ellens HE, Mooser VE, Cardon LR, Spraggs CF, Pandite L. Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism. Br J Cancer. 2010 Apr 27;102(9):1371-7. doi: 10.1038/sj.bjc.6605653. Epub 2010 Apr 13.

  PMID: 20389299 BACKGROUND

• Sternberg CN, Hawkins RE, Wagstaff J, Salman P, Mardiak J, Barrios CH, Zarba JJ, Gladkov OA, Lee E, Szczylik C, McCann L, Rubin SD, Chen M, Davis ID. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer. 2013 Apr;49(6):1287-96. doi: 10.1016/j.ejca.2012.12.010. Epub 2013 Jan 12.

  PMID: 23321547 BACKGROUND

• Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.

  PMID: 37146227 DERIVED

• Goldstein D, Rosenberg JE, Figlin RA, Townsend RR, McCann L, Carpenter C, Pandite L. Is change in blood pressure a biomarker of pazopanib and sunitinib efficacy in advanced/metastatic renal cell carcinoma? Eur J Cancer. 2016 Jan;53:96-104. doi: 10.1016/j.ejca.2015.10.006. Epub 2015 Dec 15.

  PMID: 26702763 DERIVED

• Sorich MJ, Kichenadasse G, Rowland A, Woodman RJ, Mangoni AA. Angiotensin system inhibitors and survival in patients with metastatic renal cell carcinoma treated with VEGF-targeted therapy: A pooled secondary analysis of clinical trials. Int J Cancer. 2016 May 1;138(9):2293-9. doi: 10.1002/ijc.29972. Epub 2016 Jan 6.

  PMID: 26685869 DERIVED

• Suttle AB, Ball HA, Molimard M, Hutson TE, Carpenter C, Rajagopalan D, Lin Y, Swann S, Amado R, Pandite L. Relationships between pazopanib exposure and clinical safety and efficacy in patients with advanced renal cell carcinoma. Br J Cancer. 2014 Nov 11;111(10):1909-16. doi: 10.1038/bjc.2014.503. Epub 2014 Oct 28.

  PMID: 25349968 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasm Metastasis

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2006
• First Posted: June 7, 2006
• Study Start: April 1, 2006
• Primary Completion: May 1, 2008
• Study Completion: December 1, 2014
• Last Updated: February 5, 2016
• Results First Posted: August 2, 2010

Record last verified: 2015-08

Locations

CL (3); GR (6); UA (5); AU (4); PA (3); AR (5); RU (10); ES (2); IE (2); LA (1); CZ (4); BR (3); LI (3); PL (7); SL (1); TU (4); GB (5); ME (3); HK (3); IN (5); NZ (3); IT (7); KR (3); CN (2)