This trial is active, not recruiting.

Condition leiomyosarcoma
Treatments gemcitabine + docetaxel, trabectedin
Phase phase 2
Sponsor Mario Negri Institute for Pharmacological Research
Collaborator PharmaMar
Start date April 2010
End date September 2016
Trial size 168 participants
Trial identifier NCT02249702, 2009-016017-24, TAUL


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
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.
trabectedin Yondelis
(Active Comparator)
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.
gemcitabine + docetaxel Gemzar

Primary Outcomes

progression free rate at 6-month
time frame: 6-month

Secondary Outcomes

best response rate
time frame: within 6 months

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: 1. Histologically proven uterine leiomyosarcoma. 2. Persistent or locally relapsed and/or metastatic disease. 3. At least one previous systemic treatment with an anthracycline ± ifosfamide or gemcitabine ± docetaxel. 4. Measurable disease, as defined by RECIST criteria. 5. ECOG PS <=2. 6. Age >= 18 years. 7. A minimum of 3 weeks since prior tumor directed therapy 8. Recovery from toxic effects of prior therapies to NCI CTC Grade 1 or lower. 9. Adequate haematological function. 10. Adequate renal function. 11. Adequate liver function. 12. Signed informed consent. Exclusion Criteria: 1. Prior exposure to Trabectedin. 2. Peripheral neuropathy, Grade 2 or higher. 3. History of other malignancies (except basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission from 5 years or more and judged of negligible potential of relapse. 4. Known CNS metastases. 5. Active viral hepatitis or chronic liver disease. 6. Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within one year before enrolment, uncontrolled arterial hypertension or arrhythmias. 7. Active major infection. 8. Other serious concomitant illnesses

Additional Information

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
Principal investigator Angiolo Gadducci, MD
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Mario Negri Institute for Pharmacological Research.