Clinical trial NCT00815945: Multicenter Trial With PegLiposomal Doxorubicin and Carboplatin Combination Chemotherapy in Gynecological Sarcomas and Mixed Epithelial-Mesenchymal Tumors
Official title: Phase II Study Evaluating PegLiposomal Doxorubicin (PLD) and Carboplatin Combination Chemotherapy in Gynecological Sarcomas and Mixed Epithelial-Mesenchymal Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mesenchymal Tumor
Carcinosarcoma
Leiomyosarcoma
Keywords: leiomyosarcoma
carcinosarcoma
mixed epithelial mesenchymal tumor
endometrial stroma sarcomas
Müllerian mixed tumors
carcinosarcoma of the uterus
mesenchymal tumors of the ovary or uterus
mixed epithelial mesenchymal tumors of the ovary or uterus
Lead sponsor: AGO Study Group
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2008-12-31
Enrollment: 41
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Anticancer activity in terms of progression-free survival time (PFS)
timeFrame: every 3 months
Secondary outcomes:
measure: Tolerability, i.e. type, frequency, severity and duration of adverse reactions (CTCAE,Version 3.0)
timeFrame: until recovery of toxicities
measure: Anticancer activity in patients with measurable or evaluable disease in terms of response rates (CR, PR, SD, PD) according to RECIST criteria
timeFrame: six months
measure: Overall survival
timeFrame: 30 months
measure: Correlation of tumor marker CA-125 with imaging methods
timeFrame: six months
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité, Campus Virchow Klinikum, Frauenklinik
city: Bonn
country: Germany
facility: Malteser Krankenhaus, Gynäkologie und Geburtshilfe
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte gGmbH, Frauenklinik
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe
city: Duesseldorf
country: Germany
facility: Evangelisches Krankenhaus Düsseldorf, Frauenklinik
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Frauenklinik
city: Frankfurt
country: Germany
facility: Klinikum der J. W. Goethe-Universität, Klinik für Gynäkologie und Geburtshilfe
city: Hamburg
country: Germany
facility: University Hospital Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Gynäkologisch-onkologische Praxis
city: Karlsruhe
country: Germany
facility: St. Vincentius Kliniken AG, Frauenklinik
city: Marburg
country: Germany
facility: Universitätsklinikum Giessen und Marburg GmbH, Klinik für Gynäkologie, Gynäkologische Endokrinologie und Onkologie
city: München
country: Germany
facility: Klinikum Großhadern, Frauenklinik
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen, Frauenklinik
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm, Universitätsfrauenklinik
city: Wiesbaden
country: Germany
facility: Dr. Horst Schmidt Kliniken GmbH, Klinik für Gynäkologie und gynäkologische Onkologie
Study officials:
affiliation: Klinikum Essen Mitte
name: Philipp Harter, MD
role: PRINCIPAL_INVESTIGATOR
References: