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

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.

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