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

Leiomyosarcoma Clinical Trial

Official title:

Phase II Study Evaluating PegLiposomal Doxorubicin (PLD) and Carboplatin Combination Chemotherapy in Gynecological Sarcomas and Mixed Epithelial-Mesenchymal Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00815945
• Other study ID #: AGO-GYN 7
• Status: Completed
• Phase: Phase 2
• First received: December 30, 2008
• Last updated: February 13, 2017
• Start date: June 2008
• Est. completion date: January 2012

Study information

• Verified date: March 2014
• Source: AGO Study Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: January 2012
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinosarcoma
• Leiomyosarcoma
• Mesenchymal Tumor
• Mixed Tumor, Mullerian
• Sarcoma

Intervention

Drug:
• PegLiposomal Doxorubicin
PegLiposomal Doxorubicin, intravenous, 40mg/m², every 28 days for up to 6 months
• Carboplatin
Carboplatin, intravenous, AUC 6, every 28 days for up to 6 months

Locations

Country	Name	City	State
Germany	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	Duesseldorf
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	Hannover
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

Sponsors (2)

Lead Sponsor	Collaborator
AGO Study Group	MSD SHARP & DOHME GmbH (formerly Essex Pharma GmbH)

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anticancer activity in terms of progression-free survival time (PFS)		every 3 months
Secondary	Tolerability, i.e. type, frequency, severity and duration of adverse reactions (CTCAE,Version 3.0)		until recovery of toxicities
Secondary	Anticancer activity in patients with measurable or evaluable disease in terms of response rates (CR, PR, SD, PD) according to RECIST criteria		six months
Secondary	Overall survival		30 months
Secondary	Correlation of tumor marker CA-125 with imaging methods		six months