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

NCT00815945 | Completed Phase 2

• 1 other identifier: AGO-GYN 7
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 15

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.

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

Outcome Measures

Primary Outcomes (1)

• Anticancer activity in terms of progression-free survival time (PFS)

  every 3 months

Secondary Outcomes (4)

• Tolerability, i.e. type, frequency, severity and duration of adverse reactions (CTCAE,Version 3.0)

  until recovery of toxicities

• Anticancer activity in patients with measurable or evaluable disease in terms of response rates (CR, PR, SD, PD) according to RECIST criteria

  six months

• Overall survival

  30 months

• Correlation of tumor marker CA-125 with imaging methods

  six months

Study Arms (1)

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; Drug: Carboplatin

Interventions

PegLiposomal Doxorubicin DRUG

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

Also known as: Caelyx

PegLiposomal Doxorubicin + Carboplatin

Carboplatin DRUG

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

PegLiposomal Doxorubicin + Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AGO Study Group: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (15)

Charité, Campus Virchow Klinikum, Frauenklinik

Berlin, 13353, Germany

Location

Malteser Krankenhaus, Gynäkologie und Geburtshilfe

Bonn, 53123, Germany

Location

Klinikum Bremen-Mitte gGmbH, Frauenklinik

Bremen, 28177, Germany

Location

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

Dresden, 01307, Germany

Location

Evangelisches Krankenhaus Düsseldorf, Frauenklinik

Düsseldorf, 40217, Germany

Location

Universitätsklinikum Essen, Frauenklinik

Essen, 45122, Germany

Location

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

Frankfurt, 60590, Germany

Location

University Hospital Hamburg-Eppendorf

Hamburg, 20251, Germany

Location

Gynäkologisch-onkologische Praxis

Hanover, 30177, Germany

Location

St. Vincentius Kliniken AG, Frauenklinik

Karlsruhe, 76135, Germany

Location

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

Marburg, 35043, Germany

Location

Klinikum Großhadern, Frauenklinik

München, 81377, Germany

Location

Universitätsklinikum Tübingen, Frauenklinik

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm, Universitätsfrauenklinik

Ulm, 89075, Germany

Location

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

Wiesbaden, 65199, Germany

Location

MeSH Terms

Conditions

Carcinosarcoma; Leiomyosarcoma

Interventions

liposomal doxorubicin; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms, Complex and Mixed; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Muscle Tissue

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Philipp Harter, MD

  Klinikum Essen Mitte

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2008
• First Posted: December 31, 2008
• Study Start: June 1, 2008
• Primary Completion: November 1, 2011
• Study Completion: January 1, 2012
• Last Updated: February 14, 2017

Record last verified: 2014-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (15)