Activity of Trabectedin or Gemcitabine + Docetaxel in Uterine Leiomyosarcoma (TAUL)
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|ClinicalTrials.gov Identifier: NCT02249702|
Recruitment Status : Completed
First Posted : September 25, 2014
Last Update Posted : December 6, 2017
The management of patients with uterine leiomyosarcomas poses many difficulties. Despite 60% of women present with disease limited to the uterus, cure rates range from 20 to 60%. Patients with metastatic disease at diagnosis or who recur after initial treatment have a dismal prognosis and, except for a subset of selected patients with completely resectable disease, the median survival is less than one year. Treatment options for recurrent/metastatic uterine leiomyosarcoma are limited. The most active drugs are doxorubicin ± ifosfamide and gemcitabine + docetaxel (GD) with response rate of 25-55% and 27-53%, respectively. Both these regimens have been increasingly used in the last years also in the adjuvant setting. For relapsed patients other drugs have been tested as single agent but negligible activity was observed.
Trabectedin (Yondelis® -T) is a marine-derived cytotoxic approved by EMEA. It is indicated for the treatment of patients with advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide or who are unsuitable to receive these agents. Among STS, activity has been mainly detected in synovial sarcoma, liposarcoma and leiomyosarcoma. Although the response rate did not exceed 10%, T was demonstrated to provide disease control, with progression arrest rates exceeding 50% and progression-free survival rates exceeding 20% at 6 months. So far no phase II studies tested the activity of T in uterine leiomyosarcoma specifically. This study is aimed at evaluating the activity of T (arm A) in advanced uterine leiomyosarcomas, having GD (arm B) as an internal control In parallel translational studies will be performed to identify factors predictive of the activity of T in this specific histotype.
|Condition or disease||Intervention/treatment||Phase|
|Leiomyosarcoma||Drug: gemcitabine + docetaxel Drug: trabectedin||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||168 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Randomized - Non Comparative - Study on the Activity of Trabectedin or Gemcitabine + Docetaxel in Metastatic or Locally Relapsed Uterine Leiomyosarcoma Pretreated With Conventional Chemotherapy|
|Study Start Date :||April 2010|
|Actual Primary Completion Date :||April 30, 2017|
|Actual Study Completion Date :||April 30, 2017|
Trabectedin 1.3 mg/m2 will be administered via a central venous catheter as a 24-hour infusion on day 1 of 21-days treatment cycles. Trabectedin treatment can be continued until progressive disease, major toxicity, patient's intolerance or unwillingness to continue treatment or medical decision by the responsible physician.
Other Name: Yondelis
Active Comparator: gemcitabine + docetaxel
Gemcitabine 900 mg/m2 will be administered via a central venous catheter on days one and eight over 90 min, followed by docetaxel 75 mg/m2 on day eight iv over 1 h. Gemcitabine+docetaxel treatment is planned for six cycles, unless there is evidence of disease progression, unacceptable toxicity or patient's intolerance or unwillingness to continue treatment, or medical decision by the responsible physician. Patients with continued response after six cycles can receive two additional cycles of combination therapy or continue with Gemcitabine alone.
Drug: gemcitabine + docetaxel
- progression free rate at 6-month [ Time Frame: 6-month ]Primary objective will be to assess the clinical benefit rate (defined as 6-month progression free rate) with trabectedin in patients with locally relapsed/metastatic uterine leiomyosarcoma pretreated with anthracycline ± ifosfamide and/or gemcitabine ± docetaxel.
- best response rate [ Time Frame: within 6 months ]response rate according to RECIST v1.0 criteria
- progression free survival [ Time Frame: 24 months ]Time from inclusion into the study to progression or death whichever comes first
- Overall survival [ Time Frame: 24 months ]time from inclusion into the study to death from any cause
- safety profile [ Time Frame: up to 30 days after the end of treatments ]Number of Patients with Serious and Non-Serious Adverse Events
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02249702
|Principal Investigator:||Angiolo Gadducci, MD||Azienda Ospedaliero Universitaria Pisana, Pisa, Italy|
|Principal Investigator:||Federica Grosso, MD||Azienda Ospedaliera Alessandria, Italy|