pazopanib_NCRCC,Ph2 STUDY

NCT01538238 | Completed Phase 2

• 1 other identifier: 2012-01-056
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Recent advances in understanding the biology and genetics of renal cell carcinoma (RCC) have led to major therapeutic implications. Von Hippel-Lindau (VHL) gene inactivation, present in the majority of sporadic forms of RCC, leads to a defective VHL protein, followed by an active transcription of hypoxia-inducible genes, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), c-kit, and others. However, the concept of VHL inactivation in RCC and the subsequent malignant phenotype is almost exclusively seen in patients with clear cell histology. The data about efficacy of VEGF receptor inhibitors for non-clear cell RCC (NCRCC) is rare until now. Recently, however, sunitinib and sorafenib showed its worth for NCRCC in extended access programs.1-3 Although it is not certain, the underlying mechanism of their action might lie in that papillary, chromophobe, and sarcomatoid type overexpress c-kit, which is also a target of both drugs and could therefore provide a therapeutic target for non-clear cell subtypes.4-7 Pazopanib is also a potent and selective, orally available, small molecule inhibitor of VEGFR-1,-2, and -3, PDGF-α, PDGF-β, and c-kit tyrosine kinases. It has been validated and licensed for advanced clear cell RCC (CCRCC).8 However, there is very few data about its efficacy for NCRCC. In this study, we try to evaluate the efficacy of pazopanib in metastatic NCRCC.

Conditions

Locally Advanced or Metastatic Non-clear Cell Type Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall response rates

  2years

Secondary Outcomes (4)

• Progression-free survival

  2years

• Overall survival

  2years

• Number of Adverse Events

  2years

• Exploratory analysis

  2years

Study Arms (1)

pazopanib

EXPERIMENTAL

pazopanib 800mg qd

Drug: pazopanib

Interventions

pazopanib DRUG

pazopanib 800mg qd until progression or unacceptable toxicity

pazopanib

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 19 years
• Subject must provide written informed consent
• Histologically confirmed confirmation of renal cell carcinoma with more than 50% of a non clear cell histologic component:
• Include papillary type, chromophobe type, unclassified cell types; Exclude collecting duct and sarcomatoid type. (including sarcomatoid type or collecting duct type should be less than 5% in total cancer tumor)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 -1
• At least one measurable lesion by RECIST 1.1, which has not been affected previously with radiotherapy
• Locally advanced or metastatic (stage IV) disease not amenable to surgery, radiotherapy, or combined modality therapy with curative intent
• Subject who received immune therapy (interleukin-2, interferon) at least 6weeks time prior to the enrollment and at least 3 weeks time requires who received mTOR inhibitor (everolimus, temsirolimus) therapy prior to the enrollment.
• Adequate organ system function as defined in the Table Definitions
• Absolute neutrophil count (ANC):1.5 X 10\^9/L
• Hemoglobin: 9 g/dL (5.6 mmol/L)
• Platelets: 100 X 10\^9/L
• Prothrombin time (PT) or international normalized ratio (INR):1.2 X ULN
• Activated partial thromboplastin time (aPTT):1.2 X ULN
• Total bilirubin:1.5 X ULN

You may not qualify if:

• Patients who have 50% or more for component of clear cell type renal cell carcinoma
• Prior malignancy cannot be included excepting for these cases: Subjects who have had another malignancy and have been disease-free for 2 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma and follicular or papillary thyroid cancer are eligible.
• History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic for 4 weeks, and have had no requirement for steroids or anti-seizure medication for 2 weeks prior to first dose of study drug. Screening with CNS imaging studies (magnetic resonance imaging \[MRI\]) is required only if clinically indicated or if the subject has a history of CNS metastases.
• Treatment with any of the following anti-cancer therapies:
• ① radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib / RFA or cryoablation within 14 days prior to the first dose of pazopanib OR
• ② Prior treatment history with angiogenesis inhibitors such as sunitinib, sorafenib, bevacizumab is not permitted (prior MET inhibitor or c-kit inhibitor are also not permitted)
• ③ Any ongoing toxicity from prior anti-cancer therapy that is \>Grade 1 and/or that is progressing in severity, except alopecia.
• Clinically significant gastrointestinal damage or disease that may affect absorption of pazopanib:
• (Active peptic ulcer disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or resection of the small bowel, history of stomy, abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28days prior to enrollment.)
• Patients(male/female) of reproductive potential who are not use an effective contraceptive method
• Pregnant, lactating women
• Corrected QT interval (QTc) \> 480 msecs
• History of any severe disease or medical condition, significant heat failure(Class II, III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)) or pulmonary dysfunction, presence of uncontrolled active infection(requiring antibiotics)
• History of clinically significant cardiac disease, arrhythmia and myocardial infarction
• Symptomatic peripheral vascular disease

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung medical Center

Seoul, South Korea

Location

MeSH Terms

Interventions

pazopanib

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Sungkyunkwan University School of Medicine, Department of Hematology and Oncology

Study Record Dates

• First Submitted: February 20, 2012
• First Posted: February 24, 2012
• Study Start: May 2, 2012
• Primary Completion: February 28, 2015
• Study Completion: November 14, 2015
• Last Updated: April 26, 2017

Record last verified: 2017-04

Locations

KR (1)