Pre-operative Administration of Sorafenib in Patients With Metastatic Renal Cell Carcinoma Undergoing Kidney Removal
7. december 2015 opdateret af: University Health Network, Toronto
Pre-operative Administration of Sorafenib in Patients With Metastatic Renal Cell Carcinoma Undergoing Cytoreductive Nephrectomy
The purpose of this study is to see if preoperative administration of Sorafenib reduces the size of the primary kidney tumour in patients with metastatic disease undergoing cytoreductive surgery.
The study will also assess the safety of preoperative Sorafenib.
The study drug, Sorafenib, will be given to patients preoperatively for 12 weeks. After a 1 week washout period the patient will then have their nephrectomy (kidney removed). Approximately 6 weeks following their nephrectomy, patients will resume on study drug until disease progression.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
This is a single centre, non-randomized, open label one arm pilot study of Sorafenib 400 mg twice daily given for 12 weeks preoperatively in patients with advanced metastatic kidney cancer scheduled for cytoreductive surgery.
Patients will be fully staged for disease progression with Brain MRI, CT, whole body Bone Scans, Kidney ultrasound and biopsy.
Additionally, patients' cardiac status will be evaluated pre-enrolment with an ECG and MUGA Scan.
Once enrolled into the study, patients will have clinic visits on weeks 2, 8 and 12 for monitoring visits with vital signs and adverse event recording plus blood evaluations for hematology and chemistry.
Patients will be called on weeks 3,5,6,7,9,10 and 11 to determine any changes in health status.
Surgery will occur at week 13, after a one week washout from study drug.
Patients will resume on study drug 6 weeks post operatively (or later, if wound is not completely healed).
Patients will continue on study drug and will be monitored every 4 weeks until disease progression, as determined by bone imaging and CT.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
19
Fase
- Fase 2
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
Ontario
-
Toronto, Ontario, Canada, M5G 2M9
- Princess Margaret Hospital, University Health Network
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- Biopsy proven RCC with a component of clear cell type histology
- Patients must have confirmed metastatic disease
- Candidate for cytoreductive nephrectomy
Adequate organ function as defined by:
- AST or ALT less than or equal to 2.5 times the upper limit of normal
- Bilirubin less than or equal to 1.5 times the upper limit of normal
- Absolute neutrophil count (ANC) greater than or equal to 1500/mL
- Platelets greater than or equal to 100,000/mL
- Hemoglobin greater than or equal to 9.0 g/dL
- Serum calcium less than or equal to 12.0 mg/dL
- Serum creatinine less than or equal to 1.5 x CL-ULN
- Male or female, 18 years of age or older
- Women of childbearing potential must NOT be pregnant (as confirmed by a negative pregnancy test)
- ECOG performance status 0 or 1 (see appendix 1 for ECOG performance status)
- Signed informed consent form indicating that the patient or acceptable representative has been informed of all parts of the trial prior to enrollment
- Willingness and ability to comply with study procedures
Exclusion Criteria:
- Presence of brain metastases during screening period
- Known hypersensitivity to Sorafenib
- Women who are breast-feeding
- Severe psychiatric or medical illness that may interfere with compliance with the study protocol or follow-up as deemed by the investigator
- 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.
- HIV-positive patients
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Sorafenib
All patients on study will be accrued to this arm.
Sorafenib (200 mg tablets x 2) will be administered orally twice a day for 12 weeks (full daily dose of 800 mg).
Patient visits for safety will be conducted at least every 4 weeks.
Sorafenib dose reductions for drug-related toxicity will be applied based on considerable prior clinical experience.
Surgery will be performed at the completion of the 13th week, allowing for a one-week "washout" period.
Sorafenib will be continued post operatively (around 6 weeks post surgery or when complete wound healing has occurred) until patient progresses or unacceptable toxicity occurs.
|
Starting dose: 400 mg (2x200mg tablets) BID (total= 800mg/day) taken orally.
The dose can be adjusted as per investigator if required due to toxicity (ex.
200mg BID, 200mg QD).
Study drug is taken for 12 weeks preoperatively.
Patients restart on study drug 6 weeks postoperatively and continue until progression or unacceptable toxicity occurs.
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
To measure primary pathological response data and determine if it relates with time to progression
Tidsramme: 12 weeks- 2 years
|
12 weeks- 2 years
|
|
Safety of preoperative Sorafenib will be assessed.
Tidsramme: 13 weeks
|
13 weeks
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Tumour vascularity.
Tidsramme: 12 weeks
|
12 weeks
|
|
Immunohistochemistry will be used to assess the effects of Sorafenib on angiogenic and tumorigenic promoters. Signals from VEGFR2, PDGF-alpha, c-KIT, Flt-3, CAIX and Raf-1 will be assessed.
Tidsramme: 13 weeks
|
13 weeks
|
|
A DNA microarray will be used for gene expression profiling of the tissue harvested at biopsy and surgery.
Tidsramme: 13 weeks
|
13 weeks
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Antonio Finelli, MD,MSc,FRCSC, University Health Network, Toronto
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol. 1999 Aug;17(8):2530-40. doi: 10.1200/JCO.1999.17.8.2530.
- Mickisch GH, Garin A, van Poppel H, de Prijck L, Sylvester R; European Organisation for Research and Treatment of Cancer (EORTC) Genitourinary Group. Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial. Lancet. 2001 Sep 22;358(9286):966-70. doi: 10.1016/s0140-6736(01)06103-7.
- Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC, Caton JR Jr, Munshi N, Crawford ED. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med. 2001 Dec 6;345(23):1655-9. doi: 10.1056/NEJMoa003013.
- Flanigan RC. Debulking nephrectomy in metastatic renal cancer. Clin Cancer Res. 2004 Sep 15;10(18 Pt 2):6335S-41S. doi: 10.1158/1078-0432.CCR-sup-040026.
- Eisen et al. Randomized phase III trial of sorafenib in advanced RCC: Impact of crossover on survival. ASCO Atlanta June 2006. Abs 4524
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. maj 2007
Primær færdiggørelse (Faktiske)
1. oktober 2012
Studieafslutning (Faktiske)
1. marts 2013
Datoer for studieregistrering
Først indsendt
28. maj 2007
Først indsendt, der opfyldte QC-kriterier
29. maj 2007
Først opslået (Skøn)
30. maj 2007
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
9. december 2015
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
7. december 2015
Sidst verificeret
1. december 2015
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Patologiske processer
- Neoplasmer efter histologisk type
- Neoplasmer
- Urologiske neoplasmer
- Urogenitale neoplasmer
- Neoplasmer efter sted
- Nyresygdomme
- Urologiske sygdomme
- Adenocarcinom
- Neoplasmer, kirtel og epitel
- Nyre-neoplasmer
- Neoplastiske processer
- Karcinom, nyrecelle
- Karcinom
- Neoplasma Metastase
- Molekylære mekanismer for farmakologisk virkning
- Enzymhæmmere
- Antineoplastiske midler
- Proteinkinasehæmmere
- Sorafenib
Andre undersøgelses-id-numre
- 06-0655-C
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