Multicenter Trial With PegLiposomal Doxorubicin and Carboplatin Combination Chemotherapy in Gynecological Sarcomas and Mixed Epithelial-Mesenchymal Tumors - Full Text View

Sponsors and Collaborators:	AGO Ovarian Cancer Study Group Essex Pharma HSK Research GmbH Wiesbaden
Information provided by:	AGO Ovarian Cancer Study Group
ClinicalTrials.gov Identifier:	NCT00815945

Purpose

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.

Condition	Intervention	Phase
Mesenchymal Tumor Carcinosarcoma Leiomyosarcoma	Drug: PegLiposomal Doxorubicin Drug: Carboplatin	Phase II

MedlinePlus related topics: Cancer Ovarian Cancer Soft Tissue Sarcoma

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Carboplatin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase II Study Evaluating PegLiposomal Doxorubicin (PLD) and Carboplatin Combination Chemotherapy in Gynecological Sarcomas and Mixed Epithelial-Mesenchymal Tumors

Further study details as provided by AGO Ovarian Cancer Study Group:

Primary Outcome Measures:

Anticancer activity in terms of progression-free survival time (PFS) [ Time Frame: every 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	40
Study Start Date:	June 2008
Estimated Study Completion Date:	June 2013
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
PegLiposomal Doxorubicin + Carboplatin: Experimental 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 Drug: Carboplatin Carboplatin, intravenous, AUC 6, every 28 days for up to 6 months

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically documented mesenchymal or mixed epithelial-mesenchymal tumor of the ovary or uterus
Patients with a primary diagnosis of FIGO I-IV uterine carcinosarcoma and optimum debulking (postoperative residual tumor < 1cm) may be enrolled only if cisplatin-ifosfamide combination therapy is not feasible.
Patients with metastatic uterine carcinosarcoma may be enrolled only if Ifosfamide/Paclitaxel combination therapy is not feasible.
Patients with metastatic leiomyosarcoma may be enrolled only if gemcitabine-docetaxel combination therapy is not feasible.
Measurable (target lesion) tumor, evaluable (non-target lesion) tumor or histological documentation
No more than one prior chemotherapy. Any prior platinum or anthracycline- containing chemotherapy must have been completed more than 6 months previously
Prior radiotherapy ≤ 25% of the hematopoietic system is allowed provided it took place more than 6 weeks before recruitment
Patients are allowed to have received prior anticancer hormone therapy or specific immunotherapy. Patients must have completed these therapies at least three weeks before recruitment to the study
All women with a theoretical possibility of pregnancy must produce a negative pregnancy test (serum or urinary) within seven days before starting treatment
General health of 0 - 2 on the ECOG score
At least 18 years of age
Estimated life expectancy above 12 weeks
At least 3 weeks since major surgery
Appropriate hematologic, renal and hepatic function in accordance with the following definitions:
Absolute neutrophil count (ANC) ≥ 1.5 × 109 /l
Platelets ≥ 100 × 10 9/l
Total bilirubin ≤ 1.25 times upper limit of normal
Estimated GFR ≥ 50 ml/min
LVEF > 50 %
Informed consent must be obtained from all patients.

Exclusion Criteria:

More than one prior chemotherapy (or radiochemotherapy)
Active infection or other serious medical impairment liable to affect the patient's ability to receive treatment according to protocol.
Administration of other chemotherapy drugs or other anticancer hormone treatments during the study.
History of clinically manifest atrial or ventricular arrhythmia (> LOWN II) and congestive heart failure, even if controlled by drugs (NYHA class > II). Documented myocardial infarction within 6 months before study enrollment.
Pregnant or breastfeeding women, or women not practicing appropriate birth control methods
Participation in another study using experimental drugs within the last 30 days
Any other conditions or therapies which the physician believes might put the patient at risk or impair the study objective.
Known hypersensitivity to carboplatin or pegylated liposomal doxorubicin

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00815945

Contacts

Contact: Philipp Harter, MD	+49611433234	philipp.harter@hsk-wiesbaden.de
Contact: Gabriele Elser	+4961188046720	gelser@ago-ovar.de

Locations

Germany
Dr. Horst Schmidt Kliniken GmbH, Klinik für Gynäkologie und gynäkologische Onkologie	Recruiting
Wiesbaden, Germany, 65199
Contact: Philipp Harter, MD +4961143 ext 3234 philipp.harter@hsk-wiesbaden.de
Contact: Belinda Thorwirth +4961143 ext 3234 gyntherapie.hsk-wiesbaden@arcor.de
Principal Investigator: Philipp Harter, MD
Universitätsklinikum Freiburg, Department Universitäts-Frauenklinik	Not yet recruiting
Freiburg, Germany, 79106
Contact: Annette Hasenburg, MD, PhD +49761270 ext 3002 annette.hasenburg@uniklinik-freiburg.de
Principal Investigator: Annette Hasenburg, MD, PhD
Sub-Investigator: Beate Rautenberg, MD
Universitätsklinikum Tübingen, Frauenklinik	Not yet recruiting
Tübingen, Germany, 72076
Contact: Erich Solomayer, MD, PhD +49707129 ext 80776 ufk.studienzentrale@med.uni-tuebingen.de
Principal Investigator: Erich Solomayer, MD, PhD
Sub-Investigator: Regina Fugunt, MD
Sub-Investigator: Karin Schumacher, MD
Internistische Gemeinschaftspraxis Dr. med. Ursula Vehling-Kaiser, Dr. med. Doris Greif; Hämatologie, Onkologie und Sportmedizin	Not yet recruiting
Landshut, Germany, 84028
Contact: Ursula Vehling-Kaiser, MD +49871275381 studien@vehling-kaiser.de
Principal Investigator: Ursula Vehling-Kaiser, MD
Sub-Investigator: Doris Greif, MD
Sub-Investigator: Barbara Rieder, MD
St. Vincentius Kliniken AG, Frauenklinik	Not yet recruiting
Karlsruhe, Germany, 76135
Contact: Anne Staehle, MD +4972181979419 anne.staehle@web.de
Principal Investigator: Anne Staehle, MD
Klinikum Hanau GmbH, Frauenklinik	Not yet recruiting
Hanau, Germany, 63450
Contact: Thomas Mueller, MD, PD +4961812962510 thomas_mueller@klinikum-stadt-hanau.de
Principal Investigator: Thomas Mueller, MD, PD
Sub-Investigator: Roland Fricker, MD
Med. Hochschule Hannover, Frauenklinik	Not yet recruiting
Hannover, Germany, 30625
Contact: Peter Hillemanns, MD, PhD +495115329728 Hillemanns.Peter@mh-hannover.de
Principal Investigator: Peter Hillemanns, MD, PhD
Sub-Investigator: Franziska Rinnau, MD
Sub-Investigator: Frauke Kramer, MD
Universitätsklinikum Giessen und Marburg GmbH, Klinik für Gynäkologie, Gynäkologische Endokrinologie und Onkologie	Recruiting
Marburg, Germany, 35043
Contact: Klaus Baumann, MD +4964215866491 office-marburg@ago-ovar.de
Contact: Helke Naujok +4964215866491 office-marburg@ago-ovar.de
Principal Investigator: Klaus Baumann, MD
Sub-Investigator: Dana Knoell, MD
Sub-Investigator: Ellen Mann, MD
Universitätsklinikum Ulm, Universitätsfrauenklinik	Recruiting
Ulm, Germany, 89075
Contact: Rolf Kreienberg, MD, PhD +4973150027606 rolf.kreienberg@uniklinik-ulm.de
Principal Investigator: Rolf Kreienberg, MD, PhD
Sub-Investigator: Christian Kurzeder, MD
Ostalb-Klinikum Aalen, Frauenklinik	Not yet recruiting
Aalen, Germany, 73430
Contact: Karsten Gnauert, MD +4907361551401 karsten.gnauert@ostalb-klinikum.de
Principal Investigator: Karsten Gnauert, MD
Sub-Investigator: Hans Stimmer, MD
Otto-von-Guericke-Universität, Klinik für Frauenheilkunde u. Geburtshilfe	Not yet recruiting
Magdeburg, Germany, 39108
Contact: Joachim Bischoff, MD +493916717438 joachim.bischoff@med.ovgu.de
Principal Investigator: Joachim Bischoff, MD
Sub-Investigator: Heike Heuer, MD
Sub-Investigator: Daria Sevcenkova, MD
Sub-Investigator: Laura Taran-Munteanu, MD
Sub-Investigator: Kerstin Wollschlaeger, MD
Gynäkologisch-onkologische Praxis	Not yet recruiting
Hannover, Germany, 30177
Contact: Hans-Joachim Lueck, MD, PhD +495116555280 info@go-praxis-hannover.de
Principal Investigator: Hans-Joachim Lueck, MD, PhD
Klinikum Offenbach GmbH, Klinik für Gynäkologie und Geburtshilfe	Not yet recruiting
Offenbach, Germany, 63069
Contact: Jens Kosse +496984050 jenskosse@web.de
Principal Investigator: Jens Kosse
Sub-Investigator: Christiane Fiedler, MD
Sub-Investigator: Elisa Lautz, MD
Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik f. Gynäkologie u. Geburtshilfe	Not yet recruiting
Kiel, Germany, 24105
Contact: Felix Hilpert, MD +494315972100 fhilpert@email.uni-kiel.de
Principal Investigator: Felix Hilpert, MD
Sub-Investigator: Gunnar Krause, MD
Sub-Investigator: Elna Kuehnle, MD
Sub-Investigator: Lars Venhoff, MD
Universitätskrankenhaus Hamburg-Eppendorf, Klinik u. Poliklinik f. Frauenheilkunde u. Geburtshilfe	Not yet recruiting
Hamburg, Germany, 20251
Contact: Sven Mahner, MD +4940428038172 s.mahner@uke.uni-hamburg.de
Sub-Investigator: Volkmar Mueller, MD
Principal Investigator: Sven Mahner, MD
Sub-Investigator: Linn Woelber, MD
Charité, Campus Virchow Klinikum, Frauenklinik	Recruiting
Berlin, Germany, 13353
Contact: Jalid Sehouli, MD, PhD +4930450564404 sehouli@aol.com
Principal Investigator: Jalid Sehouli, MD, PhD
Sub-Investigator: Radoslav Chekerov, MD
Sub-Investigator: Guelten Oskay-Oezcelik, MD
Evangelisches Krankenhaus Düsseldorf, Frauenklinik	Not yet recruiting
Duesseldorf, Germany, 40217
Contact: Werner Meier, MD, PhD +492119191405 wmeier1620@aol.com
Principal Investigator: Werner Meier, MD, PhD
Sub-Investigator: Agatha Rack
Klinikum Bremen-Mitte gGmbH, Frauenklinik	Recruiting
Bremen, Germany, 28177
Contact: Willibald Schroeder, MD, PhD +494214970 willibald.schroeder@klinikum-bremen-mitte.de
Principal Investigator: Willibald Schroeder, MD, PhD
Sub-Investigator: Tanja Friepoertner, MD
Sub-Investigator: Nicole Stahmann, MD
Universitätsklinikum Essen, Frauenklinik	Recruiting
Essen, Germany, 45122
Contact: Pauline Wimberger, MD, PD +492017232245 pauline.wimberger@uk-essen.de
Principal Investigator: Pauline Wimberger, MD
Sub-Investigator: Bahriye Aktas, MD
Sub-Investigator: Rainer Kimmig, MD, PhD
Sub-Investigator: Michael Wehling, MD
Malteser Krankenhaus, Gynäkologie und Geburtshilfe	Recruiting
Bonn, Germany, 53123
Contact: Martina Gropp, MD +492286481260 martina.gropp@malteser.de
Principal Investigator: Martina Gropp, MD
Elblandkliniken Meißen-Radebeul GmbH & Co KG, Gynaekologie	Not yet recruiting
Radebeul, Germany, 01445
Contact: Barbara Richter, MD +493518333500 barbara.richter@elblandkliniken.de
Principal Investigator: Barbara Richter, MD
Sub-Investigator: Irina Scharfe
Sub-Investigator: Katja Schulze, MD
Sub-Investigator: Kerstin Ulbicht, MD
Klinikum der J. W. Goethe-Universität, Klinik für Gynäkologie und Geburtshilfe	Recruiting
Frankfurt, Germany, 60590
Contact: Lars Hanker, MD +496963016850 hanker@med.uni-frankfurt.de
Principal Investigator: Lars Hanker, MD
Sub-Investigator: Friderike Fornoff, MD

Sponsors and Collaborators

AGO Ovarian Cancer Study Group

Essex Pharma

HSK Research GmbH Wiesbaden

Investigators

Principal Investigator:

Philipp Harter, MD

HSK, Dr. Horst Schmidt Kliniken

Responsible Party:	AGO Ovarian Cancer Study Group ( Gabriele Elser )
Study ID Numbers:	AGO-GYN 7
Study First Received:	December 30, 2008
Last Updated:	December 30, 2008
ClinicalTrials.gov Identifier:	NCT00815945
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices; Germany: Ethics Commission