Randomized Multicenter Trial With SU11248 Evaluating Dosage,Tolerability,Toxicity and Effectiveness of a Multitargeted Receptor Tyrosine Kinase Inhibitor
Ovarian cancer is most often recognized in advanced clinical state, the initial therapeutic strategies consist of a platinum containing chemotherapy subsequent to primary surgery. Although initially responsive to platinum-paclitaxel containing chemotherapy, a significant number of patients will show tumor progression during first line chemotherapy or relapse within six months after completion of first line chemotherapy, therefore being characterized as chemotherapy resistant. Any second line chemotherapy will result in approximately 10% of overall response, underlining the poor prognosis for these patients with an estimated median overall survival of 20 weeks.
In addition to conventional chemotherapeutics, so called small molecules are of high interest to establish new strategies in chemotherapy-refractory ovarian cancer (and in the long run first line chemotherapy). SU11248 is a polytargeting tyrosine kinase inhibitor.
SU11248 has demonstrated clinical efficacy in kidney cancer and GIST, further clinical trials have been initiated in other tumor entities. Growth pattern and biological targets present in ovarian cancer indicate that SU11248 might be a promising compound for the treatment of ovarian cancer. Especially, VEGFR, PDGFR and c-kit are specific targets for SU11248, which are expressed in ovarian cancer. The different targets of SU11248 provide a potential advantage of this compound compared to single-target molecules in chemotherapy-refractory ovarian cancer.
Platinum Refractory Epithelial Ovarian Cancer
Primary Cancer of the Peritoneum
Cancer of the Fallopian Tube
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial in Platinum-refractory Ovarian Cancer: A Randomized Multicenter Trial With SU11248 to Evaluate Dosage, Tolerability, Toxicity and Effectiveness of a Multitargeted Receptor Tyrosine Kinase Inhibitor Monotherapy|
- objective response rate [ Time Frame: one year ] [ Designated as safety issue: No ]
- tolerability and toxicity, overall survival, duration of response, time to progression, stable disease [ Time Frame: one year ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2007|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
Subjects will receive open-label sunitinib = SU11248 at a dose of 50.0 mg once daily. After 28 days, treatment will be paused for 14 days and cycle one is completed, followed by resumption of therapy as cycle one for up to one year (therapy can be continued in case of tumor response and benefit for the patient for more than one year).
Sunitinib, oral, 50mg once daily, 28 days then paused for 14 days, for up to one year
Other Name: Sutent, Sunitinib, SU011248
Subjects will receive open-label sunitinib = SU11248 at a dose of 37.5 mg once daily continuously. Treatment period up to one year (therapy can be continued in case of tumor response and benefit for the patient for more than one year).
Sunitinib, oral, 37,5 mg once daily continuously, up to one year
Other Name: SUTENT, Sunitinib, SU011248
This study in patients with ovarian cancer refractory to platinum based chemotherapy is designed as a randomized, 2-schedule and dose-level, open-label, multicenter phase II study to select the better dose and schedule arm for further investigation.
72 patients will be randomized in a 1:1 ratio to receive oral SU11248 therapy either 37.5 mg/day continuously or 50mg/day for 4 weeks followed by 14 days off.
Patients will get outpatients treatment. At screening the patients' eligibility will be assessed, their baseline and demographic characteristics obtained, and the baseline values for the effect variables collected. Patients with measurable lesions as well as non-measurable disease will be included into this trial. Measurable lesion will be documented by CT or MRI scan and CA-125 values, non-measurable lesions will be monitored by analysis of CA°125 levels.
The patients' safety will be monitored during and up to 30 days after termination of SU11248 therapy.
In patients with measurable lesions at baseline, the (post)-treatment values for effect according to the RECIST criteria will be collected as shown in table 6. In case of CR or PR, a confirmatory CT or MRI scan is required after an interval of at least four weeks. Antitumor effects according to CA°125 levels will be determined in the same time intervals and, in addition, 28 days after last SU11248 application in patients with CA°125 response according to GCIG guidelines during therapy.
For post study follow-up, patients and/or their physicians will be contacted via phone for overall survival and TTP (including the method of diagnosis and additional treatment) every 2 months for their life time.
|Malterser-Krankenhaus Bonn-Rhein/Sieg, Frauenklinik|
|Bonn, Germany, 53123|
|Klinikum Bremen-Mitte gGmbH, Frauenklinik|
|Bremen, Germany, 28177|
|Universitätsklinikum Carl Gustav Carus, Klinik u. Poliklinik für Frauenheilkunde und Geburtshilfe|
|Dresden, Germany, 01307|
|Essen, Germany, 45122|
|Klinikum der JWG Universität Frankfurt, Universitätsfrauenklinik|
|Frankfurt am Main, Germany, 60591|
|Universitätsklinikum Freiburg, Department Universitäts-Frauenklinik|
|Freiburg, Germany, 79106|
|Klinikum der Ernst-Moritz-Universität, Klinik u. Poliklinik für Gyn. - u. Geb.Hilfe|
|Greifswald, Germany, 17487|
|Med. Hochschule Hannover, Frauenklinik|
|Hannover, Germany, 30625|
|St. Vincentius Kliniken AG, Frauenklinik|
|Karlsruhe, Germany, 76135|
|Universitätsklinikum Schleswig-Holstein Campus Kiel, Klinik f. Gynäkologie u. Geburtshilfe|
|Kiel, Germany, 24105|
|Otto-von-Guericke-Universität, Klinik für Frauenheilkunde und Geburtshilfe|
|Magdeburg, Germany, 39108|
|Universitätsklinikum Gießen u. Marburg, Standort Marburg, Klinik f. Gynäkologie, Gyn. Endokrinologie u. Onkologie|
|Marburg, Germany, 35043|
|Elblandkliniken Meißen-Radebeul GmbH, Gynäkologie|
|Radebeul, Germany, 01445|
|Universitätsklinikum Tübingen, Frauenklinik|
|Tübingen, Germany, 72076|
|Ulm, Germany, 89075|
|Dr. Horst Schmidt Kliniken GmbH, Klinik f. Gynäkologie u. Gyn. Onkologie|
|Wiesbaden, Germany, 65199|
|Principal Investigator:||Uwe Wagner, MD, PhD||Universitätsklinikum Gießen u. Marburg, Klinik f. Gynäkologie, Gyn. Endokrinologie u. Onkologie|