Evaluate the Efficacy of Sorafenib in Renal Cell Carcinoma Patients After a Radical Resection of the Metastases
A Randomized, Open Label, Multicenter Phase 2 Study, to Evaluate the Efficacy of Sorafenib in Patients With Advanced Renal Cell Carcinoma (RCC) After a Radical Resection of the Metastases
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Detailní popis
Advanced RCC presents poor prognosis, because its pathogenesis is not clearly understood. However, up-regulation of the Ras pathway is thought to play a role.
VEGF expression could represent independent prognostic factors for survival possibly linking expression of this protein with clinical outcome.
Sorafenib is a potent inhibitor of both Raf-kinase and VEGF R2 signalling The anti-tumoral activity of Sorafenib was clearly demonstrated in phase III trial regarding advanced pretreated RCC.
Surgical removal of metastatic disease could potentially increase the disease control rate.
Particularly in patients with a disease free interval post nephrectomy of at least 1 year, with one small metastatic lesion, metastasectomy could represents an important therapeutic approach.
After a radical resection of the metastatic disease is unclear if an anti-tumoral systemic therapy may increase patient survival.
In summary, both the preclinical and clinical data support further evaluation of Sorafenib in RCC patients.
Typ studie
Typ studie
Zápis (Očekávaný)
Zápis
Fáze
Fáze
- Fáze 2
Kontakty a umístění
Studijní místa
-
-
-
Alba, Itálie
- Cinzia Ortega
-
Aviano, Itálie
- Alessandra Bearz
-
Brescia, Itálie
- Alfredo Berruti
-
Brindisi, Itálie
- Saverio Cinieri
-
Cagliari, Itálie
- Francesco Atzori
-
Cremona, Itálie
- Rodolfo Passalaqua
-
Firenze, Itálie
- Francesco Di Costanzo
-
Lecce, Itálie
- Vincenzo Emanuele Chiuri
-
Novara, Itálie
- Alessandra Mosca
-
Palermo, Itálie
- Vittorio Gebbia
-
Roma, Itálie
- Enrico Cortesi
-
Roma, Itálie
- Francesco Cognetti
-
San Giovanni Rotondo, Itálie
- Franco Morelli
-
-
Mi
-
Milan, Mi, Itálie, 20156
- Istituto Tumori Milano
-
-
Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
INCLUSION CRITERIA
- Age ≥ 18 years
- Patients with cytological or histological diagnosis of Renal Cell Carcinoma (RCC)
- Absence of residual lesions following surgical removal of metastatic disease. Assessment must be performed by CT-scan or MRI
- Histologically proven disease free margins of resected surgical specimen
- No more than three months from radical resection on metastases.
- ECOG Performance Status of 0 or 2
- Life expectancy of at least 12 weeks.
- Adequate bone marrow, liver 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 (ANC) >1,500/mm3
- Platelet count 100,000/ml
- Total bilirubin < 1.5 times the upper limit of normal
- ALT and AST < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer)
- Alkaline phosphatase 4 x ULN
- PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.] For patients on warfarin, close monitoring of at least weekly evaluations will be performed, until INR is stable based on a measurement at pre-dose, as defined by the local standard of care.
- Serum creatinine < 1.5 x upper limit of normal
- Amylase and lipase <1.5 X upper limit of normal
- Signed informed consent must be obtained prior to any study specific procedures
EXCLUSION CRITERIA:
- Prior systemic treatment for metastatic RCC. It is allowed an adjuvant or neoadjuvant therapy before or after nephrectomy if stopped at least 6 months before the resection of metastatic lesion/s.
- History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension (>= 160 mmHg systolic and/or 90 mmHg diastolic).
- History of HIV infection or chronic hepatitis B or C
- Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
- Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies)
- Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
- History of organ allograft
- Patients with evidence or history of bleeding diathesis
- Patients undergoing renal dialysis
- History of other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease condition that contraindicates use of an investigational drug or patient at high risk from treatment complications
- Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1) or any cancer curatively treated > 3 years prior to study entry.
- Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry.
- Radiotherapy during study or within 3 weeks of start of study drug.
- Major surgery within 4 weeks of start of study
- Autologous bone marrow transplant or stem cell rescue within 4 months of study
- Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. (G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator, however they may not be substituted for a required dose reduction.) (Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study)
- Investigational drug therapy outside of this trial during or within 4 weeks of study entry
- Prior exposure to the study drug.
- Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and two weeks after the completion of trial.
- Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
- Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
- Patients unable to swallow oral medications
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Dvojnásobek
Počet zbraní
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
|---|---|
|
Experimentální: Sorafenib
Active Arm
|
sorafenib 400 mg bid
Ostatní jména:
|
|
Žádný zásah: Best Supportive Care
Comparator
|
Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Recurrence Free Survival
Časové okno: December 2011 - December 2014 (3 years)
|
Efficacy of Sorafenib compared with BSC, in RCC patients that have undergone radical resection of recurrent metastatic disease, after prior nephrectomy.
The primary efficacy endpoint is Recurrence Free Survival (RFS),
|
December 2011 - December 2014 (3 years)
|
Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Overall Survival
Časové okno: December 2011 - December 2014 (3 years)
|
December 2011 - December 2014 (3 years)
|
|
|
Safety Profile
Časové okno: December 2011 - December 2014 (3 years)
|
Physical examination, vital signs, Red blood count: haemoglobin, hematocrit, platelet count, white blood cell count.
WBC should include differential neutrophil, lymphocyte, monocyte, basophil and eosinophil counts.
Electrolyte panel: sodium, potassium, chloride and corrected calcium.Chemistry panel: AST, ALT, bilirubin, alkaline phosphatase, uric acid, total protein, albumin, calcium, lipase, amylase, phosphate, LDH, glucose, creatinine,BUN, and bicarbonate.
Coagulation panel: PT, PT-INR, PTT.
Urinalysis, Adverse event
|
December 2011 - December 2014 (3 years)
|
|
Vascular endothelial growth factors (VEGF) levels in BSC and Sorafenib arm.
Časové okno: December 2011 - December 2014 (3 years)
|
December 2011 - December 2014 (3 years)
|
Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Vyšetřovatelé
Vyšetřovatelé
- Studijní židle: Giuseppe Procopio, MD, Istituto Tumori Milano
Publikace a užitečné odkazy
Užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia
Začátek studia
Primární dokončení (Aktuální)
Primární dokončení
Dokončení studie (Očekávaný)
Dokončení studie
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Novotvary podle histologického typu
- Novotvary
- Urologické novotvary
- Urogenitální novotvary
- Novotvary podle místa
- Onemocnění ledvin
- Urologická onemocnění
- Adenokarcinom
- Novotvary, žlázové a epiteliální
- Novotvary ledvin
- Karcinom, renální buňka
- Karcinom
- Molekulární mechanismy farmakologického působení
- Inhibitory enzymů
- Antineoplastická činidla
- Inhibitory proteinkinázy
- Sorafenib
Další identifikační čísla studie
Další identifikační čísla studie
- GP1
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .