A Phase II, Opened, Not Controlled and Multicentric Clinical Trial of Pazopanib in Monotherapy to Determine Efficiency and Safety in Second-line of Treatment in Patients With Carcinoma of Advanced Renal Cells That Have Progressed or Have Not Tolerated the First Line of Treatment With Tyrosine Kinase Inhibitor
1. Signed Inform Consent
2. Age ≥ 18
3. Histologically confirmed diagnosis of clear cell renal carcinoma metastatic or
locally recurrent unresectable.
4. Patients must have received only a first-line treatment with a Tyrosine Kinase
Inhibitor. Patients must have progressed during treatment or within three months
after stopping treatment with these agents. Patients who discontinued treatment with
a Tyrosine Kinase Inhibitor for unacceptable toxicity are also eligible for the
5. Patients must have been previously treated by nephrectomy with removal of the primary
tumor, except that there is a contraindication (eg liver I extensive bone metastatic
disease or primary tumor smaller than 5 cm).
6. Patients with ECOG PS 0 or 1.
7. To be included in the study, the renal tumor should be classified in a group of low
or intermediate risk according to the Motzer classification.
8. Eligibility criteria under RECIST v.1.1
9. Adequate hematologic function:
Absolute neutrophil count ≥ 1.5 x 109 / L Platelet count ≥ 100 x 109 / L Hemoglobin ≥
9 g / dL (5.6 mmol / L). Prothrombin time (PT) or international normalized ratio
(INR) ≤ 1.2 X ULN. Activated partial thromboplastin time (APTT) ≤ 1.2 X ULN
10. Adequate hepatic function:
total bilirubin ≤ 1.5 X ULN ALT ≤ 2.5 x ULN
11. Adequate renal function:
Serum creatinine ≤ or 1.5 mg / dL (133 mol / L). If> 1.5 mg / dL, then the calculated
creatinine clearance has to be ≥ 50 mL / min (Appendix 1).
Urine protein / creatinine ratio <1.
12. Can be included in the study of both fertile and infertile women.
1. Previous malignancy. May be included in the study patients with a disease-free
interval of 5 years at the time of inclusion in the study and patients with
non-melanoma skin carcinoma completely resected or carcinoma in situ treated
2. Previous treatment with more then one Tyrosine Kinase Inhibitor or more than one
previous traditional regime (eg, chemotherapy, immunotherapy or chemo-immunotherapy).
3. Known history or clinical evidence of nervous system metastases or leptomeningeal
carcinomatosis, except that metastases in the central nervous system have been
previously treated, are asymptomatic and not requiring treatment with corticosteroids
or anticonvulsant medication within six months before the first administration of
4. Clinically significant gastrointestinal disorders that may increase the risk of
5. Clinically significant gastrointestinal disorders which may affect the absorption of
6. Presence of uncontrolled infection.
7. ECG QT interval longer than 480 milliseconds, according to the Bazett formula.
8. History of one or more of the following cardiovascular conditions within the last 6
months prior to inclusion:
Cardiac angioplasty or stent placement Myocardial infarction Unstable angina Surgery
or coronary bypass Symptomatic peripheral vascular disease
9. Congestive heart failure Class III or IV, as defined by the New York Heart
10. Poorly controlled hypertension (defined as systolic blood pressure ≥ 140 mmHg or
diastolic blood pressure ≥ 90 mmHg).
11. History of stroke (including transient ischemic attack), pulmonary embolism or deep
vein thrombosis not treated within 6 months.
12. Major surgery or major trauma within 28 days prior to administering the first dose of
study and / or presence of any unhealed wound, fracture, or ulcer (not considered
major procedures such as venous catheter placement with or without a reservoir).
13. Evidence of bleeding diathesis or active bleeding.
14. Endobronchial lesions known and / or lesions infiltrating major pulmonary vessels.
15. Hemoptysis greater than 2.5 milliliters in the 8 weeks before the first
administration of study drug.
16. Any medical condition, psychiatric or any other nature, unstable or severe, which
could interfere with patient safety, with the ability to give informed consent or
compliance with study procedures.
17. Inability or lack of willingness to discontinue the use of banned drugs listed in in
the previous 14 days, or the time equivalent to 5 half-lives (whichever is greater)
at baseline and during treatment with pazopanib.
18. Treatment with any of the following antineoplastic therapy: radiation therapy,
surgery, tumor embolization, chemotherapy, immunotherapy, biologic therapies,
investigational therapies or hormone treatments within 14 days, or the time
equivalent to 5 half-lives (whichever is greater), to the administration of the first
dose of pazopanib.
19. Any unresolved toxicity from previous cancer therapies> Grade 1 and / or is getting
worse in intensity, except for alopecia.
20. Patients who are at risk of hypersensitivity to pazopanib.
21. Pregnant or lactating women