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

NCT ID: NCT00815945

Last Updated: 2017-02-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2012-01-31

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.

Conditions

Mesenchymal Tumor; Carcinosarcoma; Leiomyosarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

PegLiposomal Doxorubicin

Intervention Type: DRUG

PegLiposomal Doxorubicin, intravenous, 40mg/m², every 28 days for up to 6 months

Carboplatin

Intervention Type: DRUG

Carboplatin, intravenous, AUC 6, every 28 days for up to 6 months

Interventions

PegLiposomal Doxorubicin

PegLiposomal Doxorubicin, intravenous, 40mg/m², every 28 days for up to 6 months

Intervention Type: DRUG

Carboplatin

Carboplatin, intravenous, AUC 6, every 28 days for up to 6 months

Intervention Type: DRUG

Other Intervention Names

Caelyx

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

AGO Study Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philipp Harter, MD

Role: PRINCIPAL_INVESTIGATOR

Klinikum Essen Mitte

Locations

Charité, Campus Virchow Klinikum, Frauenklinik

Berlin, , Germany

Malteser Krankenhaus, Gynäkologie und Geburtshilfe

Bonn, , Germany

Klinikum Bremen-Mitte gGmbH, Frauenklinik

Bremen, , Germany

Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe

Dresden, , Germany

Evangelisches Krankenhaus Düsseldorf, Frauenklinik

Düsseldorf, , Germany

Universitätsklinikum Essen, Frauenklinik

Essen, , Germany

Klinikum der J. W. Goethe-Universität, Klinik für Gynäkologie und Geburtshilfe

Frankfurt, , Germany

University Hospital Hamburg-Eppendorf

Hamburg, , Germany

Gynäkologisch-onkologische Praxis

Hanover, , Germany

St. Vincentius Kliniken AG, Frauenklinik

Karlsruhe, , Germany

Universitätsklinikum Giessen und Marburg GmbH, Klinik für Gynäkologie, Gynäkologische Endokrinologie und Onkologie

Marburg, , Germany

Klinikum Großhadern, Frauenklinik

München, , Germany

Universitätsklinikum Tübingen, Frauenklinik

Tübingen, , Germany

Universitätsklinikum Ulm, Universitätsfrauenklinik

Ulm, , Germany

Dr. Horst Schmidt Kliniken GmbH, Klinik für Gynäkologie und gynäkologische Onkologie

Wiesbaden, , Germany

Countries

Germany

Other Identifiers

AGO-GYN 7

Identifier Type: -

Identifier Source: org_study_id