| Eligibility |
Inclusion Criteria:
1. Patients with locally advanced or metastatic renal cell carcinoma with a clear cell
component confirmed histologically by biopsy.
2. Patients eligible for cytoreductive nephrectomy according to their surgical risk
established in routine clinical practice at the site.
3. Age = 18 years.
4. Patients with an ECOG (Eastern Cooperative Oncology Group) performance status of
between 0 and 1.
5. Patients with appropriate organ and bone marrow function within 4 weeks prior to
starting treatment with cabozantinib:
- Leukocyte count > 4,000 cells/µL
- Hemoglobin > 9 g/dL
- Platelet count > 100,000/mm3
- Serum creatinine < 2.0 mg/dL or serum creatinine clearance > 30 mL/min (according
to the Cockcroft-Gault formula (Cockcroft and Gault 1976).
- Preserved liver function: alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) < 2.5 x upper limit of normal (ULN) in the absence of
liver metastases; < 5 x ULN in the case of liver metastases.
- Lipase < 2 x ULN. Amylase < 2 x ULN.
- INR (international normalized ratio) and APTT (activated partial thromboplastin
time) = 1.5 x ULN of the site. This only applies to patients who are not
receiving therapeutic anticoagulation; patients receiving therapeutic
anticoagulation with low molecular weight heparins should maintain stable doses.
6. Patients with no radiological or clinical evidence of pancreatitis.
7. Patients with evaluable tumor disease according to the RECIST criteria 1.1 (Eisenhauer
et al. 2009).
8. Patients with controlled blood pressure (systolic < 145 mmHg; diastolic blood pressure
< 90 mmHg).
9. Patients who sign informed consent to participate in the study.
10. Patients may have brain metastases appropriately treated with radiation therapy and/or
surgery (including radiosurgery), as long as they do not require the concomitant use
of corticosteroids.
Exclusion Criteria:
1. Patients with a second active malignant tumor.
2. Patients with tumors treated in the last 2 years.
3. Pregnant or breastfeeding women.
4. Women of child-bearing potential who do not agree to use a contraceptive method during
treatment. Women participating in the study should have undergone surgical
sterilization, be post-menopausal, or agree to use a highly effective contraceptive
method (in accordance with CTFG (clinical trial facilitation group) criteria) during
the treatment period. Patients of both sexes and their partners must use effective
contraception during treatment and, at least, up to four months after completing
treatment. Since oral contraceptives cannot possibly be considered "effective
contraceptive methods", they should be used in conjunction with another method, such
as a barrier method
5. Fertile men who do not agree to use a contraceptive method during treatment. Male
participants in the study should have undergone surgical sterilization, or agree to
use a highly effective contraceptive method (in accordance with CTFG (clinical trial
facilitation group) criteria) during the treatment period.
6. Patients with gastrointestinal disorders, including:
- Inability to take oral medication.
- Need for parenteral nutrition.
- Prior surgical procedures affecting absorption.
- Active gastrointestinal bleeding.
- Malabsorption syndrome.
- Gastrointestinal disorders that increase the risk of perforation.
7. Patients who have had any of the following conditions within the 12 months prior to
inclusion in the study: myocardial infarction, uncontrolled angina, uncontrolled
hypertension, peripheral arterial or coronary graft bypass, congestive heart failure,
stroke, or transient ischemic attack.
8. Patients with tumors that invade or affect major blood vessels, gastrointestinal
tract, or trachea/bronchi.
9. Patients with human immunodeficiency virus (HIV) infection or acquired
immunodeficiency syndrome (AIDS)-related diseases.
10. Patients with active hepatitis or hepatitis C.
11. Patients with active tuberculosis.
12. Patients with uncontrolled (Ca > 12 mg/dL) or symptomatic hypercalcemia who require
continuous treatment with bisphosphonates or denosumab.
13. Patients who have undergone major surgery within 4 weeks prior to inclusion in the
study.
14. Patients with active bleeding.
15. Patients with a recent episode of intestinal obstruction.
16. Patients who have previously received VEGF (vascular endothelial growth
factor)-targeted therapy for advanced disease.
17. Patients who have undergone radiation therapy for bone metastases within 2 weeks prior
to the first dose of cabozantinib, or any external radiation therapy within 4 weeks
prior to the first dose of cabozantinib.
18. Patients who have received an allogeneic transplant or stem cells in the last 5 years.
19. Malignant tumors within 3 years before Day 1 of Cycle 1, except for those with
negligible risk of metastasis or death and who have been treated with curative intent,
such as cervical carcinoma in situ or localized prostate cancer treated with curative
intent.
20. Patients receiving therapeutic doses of oral anticoagulants (e.g., warfarin, direct
thrombin inhibitors and Factor Xa) or antiplatelet agents (e.g., clopidogrel). The use
of low molecular weight heparins is allowed
21. Hypersensitivity to the active substance or to any of the excipients (exclude lactose
intolerant patients since each film-coated tablet contains 46.61 mg of lactose).
22. Any other clinical condition that the physician responsible for the patient considers
to be inappropriate for inclusion in the study.
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