Activity of Trabectedin or Gemcitabine + Docetaxel in Uterine Leiomyosarcoma
TAUL
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
2 other identifiers
interventional
168
1 country
34
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Apr 2010
Longer than P75 for phase_2
34 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 1, 2010
CompletedFirst Submitted
Initial submission to the registry
September 23, 2014
CompletedFirst Posted
Study publicly available on registry
September 25, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
April 30, 2017
CompletedDecember 6, 2017
December 1, 2017
7.1 years
September 23, 2014
December 5, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
progression free rate at 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.
6-month
Secondary Outcomes (1)
best response rate
within 6 months
Other Outcomes (3)
progression free survival
24 months
Overall survival
24 months
safety profile
up to 30 days after the end of treatments
Study Arms (2)
Trabectedin
EXPERIMENTALTrabectedin 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.
gemcitabine + docetaxel
ACTIVE COMPARATORGemcitabine 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.
Interventions
Eligibility Criteria
You may qualify if:
- Histologically proven uterine leiomyosarcoma.
- Persistent or locally relapsed and/or metastatic disease.
- At least one previous systemic treatment with an anthracycline ± ifosfamide or gemcitabine ± docetaxel.
- Measurable disease, as defined by RECIST criteria.
- ECOG PS \<=2.
- Age \>= 18 years.
- A minimum of 3 weeks since prior tumor directed therapy
- Recovery from toxic effects of prior therapies to NCI CTC Grade 1 or lower.
- Adequate haematological function.
- Adequate renal function.
- Adequate liver function.
- Signed informed consent.
You may not qualify if:
- Prior exposure to Trabectedin.
- Peripheral neuropathy, Grade 2 or higher.
- 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.
- Known CNS metastases.
- Active viral hepatitis or chronic liver disease.
- Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within one year before enrolment, uncontrolled arterial hypertension or arrhythmias.
- Active major infection.
- Other serious concomitant illnesses
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mario Negri Institute for Pharmacological Researchlead
- PharmaMarcollaborator
Study Sites (34)
Centro di Riferimento Oncologico
Aviano, Pordenone, Italy
Policlinico Umberto I
Roma, RM, 00186, Italy
Fondazione del Piemonte per l'Oncologia
Candiolo, Turin, Italy
Azienda ULSS 13 Regione Veneto, Ospedale di Mirano
Mirano, Venice, Italy
Ospedale Sacro Cuore Don Calabria
Negrar, Verona, Italy
Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo
Alessandria, Italy
Azienda Ospedaliera Spedali Civili di Brescia
Brescia, Italy
Presidio Ospedaliero Senatore Antonio Perrino
Brindisi, Italy
Azienda Ospedaliera per l'Emergenza Cannizzaro
Catania, Italy
Ospedale Sant'Anna
Como, Italy
Azienda Ospedaliera S. Croce e Carle
Cuneo, Italy
Azienda Ospedaliera Universitaria San Martino - IST
Genoa, Italy
Ente Ospedaliero Ospedali Galliera
Genova, Italy
Azienda USL 2 Toscana - Nuovo Ospedale San Luca
Lucca, Italy
Istituto Clinico Humanitas
Milan, Italy
Istituto Europeo di Oncologia
Milan, Italy
Istituto Nazionale dei Tumori di Milano
Milan, Italy
Istituto Nazionale dei Tumori di Milano
Milan, Italy
Azienda Ospedaliera San Gerardo
Monza, Italy
Istituto Nazionale Tumori - Fondazione Pascale
Napoli, Italy
Azienda Ospedaliero Universitaria Maggiore della Carità
Novara, Italy
Istituto Oncologico Veneto
Padua, Italy
Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello
Palermo, Italy
Azienda Ospedaliero-Universitaria di Parma
Parma, Italy
Policlinico San Matteo
Pavia, Italy
Azienda Ospadaliero-Universitaria Pisana
Pisa, Italy
Azienda Ospedaliera Regionale San Carlo
Potenza, Italy
Azienda Ospedaliera Arcispedale S. Maria Nuova
Reggio Emilia, Italy
Ospedale San Giovanni Calibita Fatebenefratelli
Roma, Italy
Policlinico Umberto I - Università Sapienza
Roma, Italy
Policlinco Universitario Agostino Gemelli
Rome, Italy
Azienda Ospedaliera Ordine Mauriziano
Torino, Italy
Azienda Ospedaliero-Universitaria di Torino - Presidio Sant'Anna
Torino, Italy
Presidio Sanitario Gradenigo
Torino, Italy
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Angiolo Gadducci, MD
Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
- PRINCIPAL INVESTIGATOR
Federica Grosso, MD
Azienda Ospedaliera Alessandria, Italy
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 23, 2014
First Posted
September 25, 2014
Study Start
April 1, 2010
Primary Completion
April 30, 2017
Study Completion
April 30, 2017
Last Updated
December 6, 2017
Record last verified: 2017-12