pazopanib_NCRCC,Ph2 STUDY

Phase 2

Completed

• Conditions: Locally Advanced or Metastatic Non-clear Cell Type Renal Cell Carcinoma
• Interventions: Drug: pazopanib

• Registration Number: NCT01538238
• Lead Sponsor: Samsung Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-02-20
• Study First Submitted QC: 2012-02-20
• Study First Posted: 2012-02-24
• Study Start: 2012-05-02
• Primary Completion: 2015-02-28
• Study Completion: 2015-11-14
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-24
• Last Update Posted: 2017-04-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

1. Patients who have 50% or more for component of clear cell type renal cell carcinoma

2. 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.

3. 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.

4. 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.

5. 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.)

6. Patients(male/female) of reproductive potential who are not use an effective contraceptive method

7. Pregnant, lactating women

8. Corrected QT interval (QTc) > 480 msecs

9. 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)

10. History of clinically significant cardiac disease, arrhythmia and myocardial infarction

11. Symptomatic peripheral vascular disease

12. Poorly controlled hypertension [the patients who have systolic blood pressure (SBP) of <140 mmHg or diastolic blood pressure (DBP) of <90mmHg regardless antihypertensive treatment are eligible. If systolic blood pressure is 140-150mmHg, blood pressure (BP) must be re-assessed in a week and SBP <150mmHg is eligible.]

13. History of cerebrovascular accident including transient ischemic attack (TIA), untreated pulmonary embolism or deep venous thrombosis (DVT) within the past 2 months.

14. Prior major operation within 28 days prior to the first dose of study drug.

15. Evidence of active bleeding or bleeding diathesis.

16. Known lesions infiltrating major pulmonary vessels(simple abut lesion is eligible)

17. Hemoptysis in excess of 2.5 mL per cough (or one half teaspoon) due to cancer within 8 weeks of the first dose of study drug.

18. Unable or unwilling to discontinue use of prohibited medications listed in protocol for at least 14 days(whichever is longer) prior to the first dose of study drug and for the duration of the study.

19. Patients who are not capable of planned F/U visits due to pre-existing psychiatric, social and family condition or geographical reason.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
pazopanib	pazopanib	pazopanib 800mg qd

Primary Outcome Measures

Name	Time	Method
Overall response rates	2years

Secondary Outcome Measures

Name	Time	Method
Number of Adverse Events	2years
Progression-free survival	2years
Overall survival	2years
Exploratory analysis	2years	c-kit protein expression,the relationship between efficacy and tumoral fibroblast growth factor receptor 1 gene amplification (FISH), the relationship between efficacy and MET mutation in papillary carcinoma, the relationship between efficacy and microvessel density and/or VEGF-R2 expression in tumor by immunohistochemistry

Trial Locations

Locations (1)

Samsung medical Center; 🇰🇷 Seoul, Korea, Republic of