Clinical trial NCT01147822: Pazopanib Versus Sunitinib in the Treatment of Asian Subjects With Locally Advanced and/or Metastatic Renal Cell Carcinoma
Official title: A Study to Evaluate Efficacy and Safety of Pazopanib Versus Sunitinib for the Treatment of Asian Subjects With Locally Advanced and/or Metastatic Renal Cell Carcinoma - A Substudy to VEG108844
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Renal Cell
Keywords: SUTENT
GW76034
Sunitinib
Renal cell carcinoma
Pazopanib
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-06-22
Enrollment: 367
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was a randomized, open label, parallel group, Phase II study to evaluate the efficacy and safety of pazopanib compared to sunitinib in Asian subjects with advanced renal cell carcinoma (RCC) who have not received prior systemic therapy for advanced or metastatic RCC.

Detailed description: Study VEG113078 is a substudy of Study VEG108844 (NCT00720941). Due to the projected limited enrollment of Asian participants into Study VEG108844, Study VEG113078 was designed to evaluate the efficacy and safety of pazopanib versus sunitinib for the treatment of Asian participants enrolled from selected Far-East Asian countries. The data for Study VEG113078 was pooled at the same time as the main study VEG108844 (NCT00720941). The subjects were centrally randomized in 1:1 ratio to receive open label study medication of either pazopanib 800mg to be administered once daily orally continuous dosing or sunitinib 50mg to be administered in 6-week cycles: 50mg orally daily for 4 weeks followed by 2 weeks off treatment. Subjects were permitted to receive supportive care throughout the study including transfusion of blood and blood products, treatment with antibiotics, anti-emetics, anti-diarrheal agents, analgesics, erythropoietin, or bisphosphonates, when appropriate. The study treatment continued until subjects experience disease progression, unacceptable toxicity, withdraw consent, or death.

Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Diagnosis of renal cell carcinoma with clear-cell component histology.
* Received no prior systemic therapy (interleukin-2, interferon-alpha, chemotherapy, bevacizumab, mTOR inhibitor, sunitinib, sorafenib or other VEGF TKI) for advanced or metastatic RCC
* Locally advanced or metastatic renal cell carcinoma Measurable disease by CT or MRI
* Karnofsky performance scale status of \>=70
* Age \>=18 years
* A female is eligible to enter and participate in this study if she is of: non-childbearing or agrees to use adequate contraception.
* Adequate organ system function
* Total serum calcium concentration \<12.0mg/dL
* Left ventricular ejection fraction \>= lower limit of institutional normal

Exclusion Criteria:

* Pregnant or lactating female (unless agrees to refrain from nursing throughout the treatment period and for 14 days following the last dose of study)-History of another malignancy (unless have been disease-free for 3 years)
* History or clinical evidence of central nervous system (CNS) metastases (unless have previously-treated CNS metastases and meet all 3 of the following criteria are: are asymptomatic, have had no evidence of active CNS metastases for \>=6 months prior to enrolment, and have no requirement for steroids or enzyme-inducing anticonvulsants)
* Clinically significant gastrointestinal abnormalities including, but not limited to: malabsorption syndrome, major resection of the stomach or small bowel that could affect the absorption of study drug, active peptic ulcer disease, known intraluminal metastatic lesion/s with suspected bleeding, 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 28 days prior to beginning study treatment
* Presence of uncontrolled infection
* Prolongation of corrected QT interval (QTc) \> 480 milliseconds
* History of any one or more of the following cardiovascular conditions within the past 12 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association
* History of cerebrovascular accident including transient ischemic attack within the past 12 months
* History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months (unless had recent DVT and have been treated with therapeutic anti-coagulating agents for at least 6 weeks)
* Poorly controlled hypertension (defined as systolic blood pressure of \>=150mmHg or diastolic blood pressure of \>=90mmHg). Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry
* Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer.
* Evidence of active bleeding or bleeding susceptibility
* Spitting/coughing up blood within 6 weeks of first dose of study drug
* Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
* Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with patient's safety, obtaining informed consent or compliance to the study
* Use any prohibited medications within 14 days of the first dose of study medication
* Use of an investigational agent, including an investigational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug
* Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors (eg. bevacizumab, sunitinib, sorafenib, etc), or are mTOR inhibitors (eg. temsirolimus, everolimus, etc).
* Is now undergoing and/or has undergone in the 14 days immediately prior to first dose of study drug, any cancer therapy (surgery, tumor embolization, chemotherapy, radiation therapy, immunotherapy, biological therapy, or hormonal therapy)
* Any ongoing toxicity from prior anti-cancer therapy that is \>Grade 1 and/or that is progressing in severity
* Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or sunitinib

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From randomization until the earliest date of disease progression or date of death from any cause, assessed up to approximately 24 months (Primary analysis cut-off date = 21-May-2012) at the same time as the main study VEG108844 (NCT00720941).
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization until date of death from any cause, assessed up to 40 months (Final OS analysis cut-off date = 30-Sep-2013) at the same time as the main study VEG108844 (NCT00720941).
measure: Overall Response Rate (ORR) as Assessed by Independent Review
timeFrame: From randomization until date of radiographic progression, assessed up to approximately 24 months (Primary analysis cut-off date = 21-May-2012) at the same time as the main study VEG108844 (NCT00720941).
measure: Time to Response
timeFrame: From randomization until date of radiographic progression, assessed up to approximately 24 months (Primary analysis cut-off date = 21-May-2012) at the same time as the main study VEG108844 (NCT00720941).
measure: Duration of Response (DOR)
timeFrame: From the date of the first documented response (CR or PR) to the date of first documented progression, assessed up to approximately 24 months (Primary analysis cut-off date = 21-May-2012) at the same time as the main study VEG108844 (NCT00720941).
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Daejeon
country: Korea, Republic of
facility: Novartis Investigative Site
city: Goyang-si, Gyeonggi-Do
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Kaohsiung Hsien
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan County
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Sheng X, Jin J, He Z, Huang Y, Zhou A, Wang J, Ren X, Ye D, Zhang X, Qin S, Zhou F, Wang B, Guo J. Pazopanib versus sunitinib in Chinese patients with locally advanced or metastatic renal cell carcinoma: pooled subgroup analysis from the randomized, COMPARZ studies. BMC Cancer. 2020 Mar 14;20(1):219. doi: 10.1186/s12885-020-6708-8.
citation: Guo J, Jin J, Oya M, Uemura H, Takahashi S, Tatsugami K, Rha SY, Lee JL, Chung J, Lim HY, Wu HC, Chang YH, Azad A, Davis ID, Carrasco-Alfonso MJ, Nanua B, Han J, Ahmad Q, Motzer R. Safety of pazopanib and sunitinib in treatment-naive patients with metastatic renal cell carcinoma: Asian versus non-Asian subgroup analysis of the COMPARZ trial. J Hematol Oncol. 2018 May 22;11(1):69. doi: 10.1186/s13045-018-0617-1.