Multicenter Trial With PegLiposomal Doxorubicin and Carboplatin Combination Chemotherapy in Gynecological Sarcomas and Mixed Epithelial-Mesenchymal Tumors
Uterine sarcomas account for less than 5% of all carcinomas of the uterine corpus. The prognosis of these patients is extremely limited. Recurrence rates of 50-60% are reported even for early-stage disease (FIGO I/II). Median overall survival is below 12 months in patients with advanced or metastatic disease.
Ovarian carcinosarcoma is extremely rare among ovarian malignancies (< 2%). That is why there is insufficient data as a basis for establishing a gold standard. As a result, these cases tend to be treated in the same way as uterine sarcomas or epithelial ovarian malignancies in clinical practice.
On the basis of data published to date on the treatment of mixed mesenchymal-epithelial tumors, it is clear that the treatments commonly used to date have limited activity while producing clinically relevant toxicity. The regimes verified so far (Cisplatin / Ifosfamide, Ifosfamide/Paclitaxel and Gemcitabine/Docetaxel) exhibit a considerable side effect spectrum and are only rarely feasible on clinical everyday life conditions, so e. g. the rate of withdrawals due to toxicity was in a study collective of selected females treated with the last combination at 40 %. The physician has to check in every individual case if one of the above mentioned combinations is feasible. The search for alternative effective and better tolerated treatment options is essential. The toxicity data on the carboplatin-PLD combination are known, and efficacy has been identified in small cohorts.
The objective of this study is to explore the efficacy of combination PLD-carboplatin treatment in a larger patient population.
Drug: PegLiposomal Doxorubicin
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study Evaluating PegLiposomal Doxorubicin (PLD) and Carboplatin Combination Chemotherapy in Gynecological Sarcomas and Mixed Epithelial-Mesenchymal Tumors|
- Anticancer activity in terms of progression-free survival time (PFS) [ Time Frame: every 3 months ] [ Designated as safety issue: No ]
- Tolerability, i.e. type, frequency, severity and duration of adverse reactions (CTCAE,Version 3.0) [ Time Frame: until recovery of toxicities ] [ Designated as safety issue: Yes ]
- Anticancer activity in patients with measurable or evaluable disease in terms of response rates (CR, PR, SD, PD) according to RECIST criteria [ Time Frame: six months ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: 30 months ] [ Designated as safety issue: No ]
- Correlation of tumor marker CA-125 with imaging methods [ Time Frame: six months ] [ Designated as safety issue: No ]
|Study Start Date:||June 2008|
|Estimated Study Completion Date:||June 2013|
|Primary Completion Date:||June 2010 (Final data collection date for primary outcome measure)|
Experimental: PegLiposomal Doxorubicin + Carboplatin
Subjects will receive PegLiposomal Doxorubicin (40mg/m²) and Carboplatin (AUC6) every 28 days. Treatment period up to 6 months (therapy can be continued in case of tumor response and benefit for the patient)
Drug: PegLiposomal Doxorubicin
PegLiposomal Doxorubicin, intravenous, 40mg/m², every 28 days for up to 6 months
Other Name: CaelyxDrug: Carboplatin
Carboplatin, intravenous, AUC 6, every 28 days for up to 6 months
This study in patients with mesenchymal or mixed epithelial mesenchymal tumors of the ovary or uterus is designed as a prospective single-arm, open - label, multicenter phase II study to evaluate the efficacy of PegLiposomal Doxorubicin and Carboplatin combination chemotherapy.
40 patients will be recruited to receive PegLiposomal Doxorubicin (PLD) in a continuous i. v. infusion of at least 60 minutes at a dose of 40 mg/m2 on Day 1, followed by a 30-minute i. v. carboplatin infusion according to AUC 6 (formula devised by Calvert et al).
Patients will get outpatients treatment. At screening the patients' eligibility will be assessed, their baseline and demographic characteristics obtained, and baseline values for the effect variables collected. Patients with measurable lesions, non-measurable lesions or histological documentation will be included into this trial. Measurable lesion and non-measurable lesions will be documented by x-ray, ultrasound, computed tomography or MRI.
The patients' safety will be monitored during therapy until recovery of toxicities.
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. CR, PR and SD have to be confirmed by a repeat measurement after an interval of at least four weeks.
Follow-up is scheduled every three months during the first two years after the end of treatment.
As from year 3 the follow-up takes place outside the study in the context of general aftercare.
|Charité, Campus Virchow Klinikum, Frauenklinik|
|Berlin, Germany, 13353|
|Malteser Krankenhaus, Gynäkologie und Geburtshilfe|
|Bonn, Germany, 53123|
|Klinikum Bremen-Mitte gGmbH, Frauenklinik|
|Bremen, Germany, 28177|
|Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe|
|Dresden, Germany, 01307|
|Evangelisches Krankenhaus Düsseldorf, Frauenklinik|
|Duesseldorf, Germany, 40217|
|Universitätsklinikum Essen, Frauenklinik|
|Essen, Germany, 45122|
|Klinikum der J. W. Goethe-Universität, Klinik für Gynäkologie und Geburtshilfe|
|Frankfurt, Germany, 60590|
|University Hospital Hamburg-Eppendorf|
|Hamburg, Germany, 20251|
|Hannover, Germany, 30177|
|St. Vincentius Kliniken AG, Frauenklinik|
|Karlsruhe, Germany, 76135|
|Universitätsklinikum Giessen und Marburg GmbH, Klinik für Gynäkologie, Gynäkologische Endokrinologie und Onkologie|
|Marburg, Germany, 35043|
|Klinikum Großhadern, Frauenklinik|
|München, Germany, 81377|
|Universitätsklinikum Tübingen, Frauenklinik|
|Tübingen, Germany, 72076|
|Universitätsklinikum Ulm, Universitätsfrauenklinik|
|Ulm, Germany, 89075|
|Dr. Horst Schmidt Kliniken GmbH, Klinik für Gynäkologie und gynäkologische Onkologie|
|Wiesbaden, Germany, 65199|
|Principal Investigator:||Philipp Harter, MD||Klinikum Essen Mitte|