Phase I/II Prospective, Open Label and Multicentric Clinical Trial to Determine the Recommended Dose (Phase I) and Efficacy of Pazopanib in Combination With Interferon Alfa 2-A (Phase II), in Patients With Advanced Renal Cell Carcinoma
1. Signed informed consent
2. Age ≥ 18 years.
3. Patients diagnosed histologically clear cell carcinoma of the kidney metastatic or
unresectable locally advanced, previously untreated. However, in Phase I may include
patients with primary tumors other than renal cell can benefit from these drugs and
patients with renal cell carcinoma treated before.
4. Performance status (ECOG) 0-1.
5. Patients must have measurable disease by RECIST criteria V 1.1. Progression should be
documented in the two months prior to study entry.
6. Patients may not have received prior treatment with anti-VEGF agents, mTOR inhibitors
or cytokines. However, in Phase I may include patients who have received any previous
7. Paraffin tumor sample should be available and collection of serum from all subjects
for biomarker analysis previously and / or during treatment with study medication.
8. Adequate Hematologic, liver and kidney functions.
9. Women of childbearing potential must be using an effective method of birth control
(abstinence, any intrauterine device [IUD] published data showing that the expected
minimum rate of failure is less than 1% per year, or any other method the published
data show that the expected minimum rate of failure is less than 1% per year) before
inclusion in the study and continue using it during the same six months after
completion. Women of childbearing age should get a negative pregnancy test in urine
or serum (minimum sensitivity 25 IU / L or equivalent units of beta fraction of human
chorionic gonadotropin [β-HCG]) during the seven days prior to the randomization.
10. Able to swallow oral compound.
11. Willingness and ability to attend scheduled visits, to follow the treatment schedule
and to undergo clinical trials and other study procedures
1. History of prior malignancies diagnosed or treated over the past 5 years except basal
cell skin cancer or prostate cancer incidentally detected previously treated.
However, patients with a history of malignancy but free of the disease over the past
5 years, or patients with a history of nonmelanoma skin carcinoma-completely-resected
or carcinoma in situ treated successfully can participate in the study .
In Phase I, patients diagnosed with other previous or concomitant malignant diseases
can be included.
2. Presence of metastases in the central nervous system (CNS) or leptomeningeal
carcinomatosis, except for patients with previously treated CNS metastases,
asymptomatic and have not needed corticosteroids or anticonvulsant drugs in the 3
months prior to administering the first dose of the drug under study. Only is
required CNS imaging studies (computed tomography [CT] or magnetic resonance imaging
[MRI]) if clinically indicated or if the individual has a history of CNS metastases.
3. Clinically significant gastrointestinal disorders may increase the risk of
gastrointestinal bleeding including, but not limited to:
Active peptic ulcer disease Known metastatic lesions with probable intraluminal
bleeding Inflammatory bowel disease (ulcerative colitis, Crohn's disease) or other
gastrointestinal disorders with increased risk of perforation History of abdominal
fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days
before the start of study treatment.
4. Clinically significant gastrointestinal abnormalities may affect the absorption of
the investigational product such as but not limited to:
Malabsorption syndrome Major resection of the stomach or small intestine Grade 3
5. Patients with active infection or other disease or serious medical condition.
6. Prolongation of the corrected QT wave (QTc)> 480 ms on baseline ECG according to the
7. Subjects with a history of one or more of the following cardiovascular disease in the
last 6 months prior to the inclusion in the study:
Angioplasty or stent placement Myocardial infarction Unstable Angina Coronary bypass
surgery Symptomatic peripheral vascular disease Congestive heart failure Class II,
III or IV New York Heart Association (NYHA)
8. Poorly controlled hypertension [defined as systolic blood pressure (SBP) ≥ 140 mmHg
or diastolic blood pressure stress (DBP) ≥ 90 mmHg] while the patient is on
Note: the commencement or adjustment of antihypertensive medication it is possible
before the patient study start. In the baseline period measure blood pressure at
least twice with a minimum interval of 24 hours. The mean values of SBP / DBP in
each blood pressure reading should be <140/90 mmHg to include the subject in the
9. Background, in the last six months prior to the inclusion of stroke (including
transient ischemic attacks), pulmonary embolism or deep vein thrombosis (DVT)
Note: may be included subjects with recent DVT who received anticoagulants for at
least 6 months.
10. Surgery or trauma in the last 28 days, or minor surgery (eg., Removal of central
venous catheter) in the last 7 days prior to inclusion or unhealed wound, fracture,
11. Evidence of active bleeding or bleeding diathesis.
12. Hemoptysis within 6 weeks prior to inclusion.
13. Pregnant or breastfeeding.
14. Any medical condition (eg. Uncontrolled infection), psychiatric or other to be
serious and / or unstable and may interfere with the safety of the patient, obtaining
informed consent or compliance with study procedures.