Phase I Trial of Sorafenib in Combination With Radiotherapy in the Treatment of Invasive Bladder Cancer With Conservative Intent
- Patients diagnosed with urothelial carcinoma of the bladder, in clinical stages T2-4a
N0 M0 (if multifocal evaluation of all lesions by biopsies), who are not candidates
for radical cystectomy by medical reasons or refusal.
- No prior treatment with radiotherapy to the bladder or systemic chemotherapy.
- Patients must be ≥ 18 years old.
- Patients must have ECOG performance status 0 to 2.
- Life expectancy of at least 12 weeks.
- Patients with adequate bone marrow, hepatic and renal function as assessed by the
following laboratory requirements to be conducted within 7 days prior to screening:
hemoglobin ≥ 9.0 g/dl absolute neutrophil count ≥ 1.500/mm3 platelets ≥ 100.000/mm3. total
bilirubin ≤ 1.5 times the upper limit of normality SGOT (AST) and/or SGPT (ALT) ≤ 2.5
times the upper limit of normality alkaline phosphatase ≤ 4 x ULN serum creatinine ≤1.5
upper limit of normality PT-INR/PTT < 1.5 x upper limit of normality creatinine clearance
≥ 40 ml/min using Cockcroft-Gaul
- Patients must give their written informed consent before any procedure related to the
study is performed; therefore, it must be given at the selection visit. The patient
must be informed that he has the right to withdraw from the study at any time,
without any kind of prejudice.
- Patients who are capable of accomplishing the study's requirements and without any
impediments to follow the instructions.
- Women of fertile age must have a negative result in the pregnancy test performed 7
days before the beginning of the administration of the study medication.
- Patients from both sexes must use adequate contraceptive methods (oral or injectable
contraceptives, intrauterine device, condom, sterilization) whilst participating in
the protocol. After the retreat of treatment with sorafenib, the contraceptive
methods must be used during 4 weeks in women and during 3 months in men.
- Patients with active infection or other serious medical conditions (autologous bone
marrow transplant or stem cell rescue within 4 months of study, patients undergoing
renal dialysis, known HIV infection or chronic hepatitis B or C, active clinically
serious infections > CTCAE Grade 2, non-healing wound, ulcer, or bone fracture).
- Abuse of substances, clinical conditions, psychological or social, that would
preclude appropriate informed consent or compliance with protocol.
- Concurrent treatment with other experimental drugs (within 30 days prior to study
- Concurrent treatment with other anti-cancer- or immunotherapy during the study or
within 4 weeks of study entry.
- Treatment wuth mitomycin C or nitrosureas during 6 weeks prior of study entry.
- History of prior malignancies within the preceding 5 years other than previously
treated basal cell carcinoma of the skin, incipient prostate cancer and in situ
- Pregnant or breast feeding patients.
- Known or suspected allergy to sorafenib.
- Cardiac disease: Congestive heart failure > class II NYHA; active CAD (myocardial
infarction more than 6 months to study entry is allowed); cardiac arrythmias
requiring anti-arrythmic therapy (beta blockers or digoxin are permitted).
- Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic
pressure > 90 mm Hg, despite optimal medical management.
- Known brain metastasis. Patients with neurological symptoms should undergo a CT
scan/MRI of the brain to exclude brain metastasis.
- Thrombotic or embolic events such as cerebrovascular accident including transient
ischemic attacks within the past 6 months.
- Patients with hydronephrosis.
- Patients with seizure disorder requiring medication (such as steroids or
- History of organ allograft.
- Patient unable to swallow oral medication.