Activity of Trabectedin or Gemcitabine + Docetaxel in Uterine Leiomyosarcoma

Leiomyosarcoma Clinical Trial

— TAUL  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02249702
• Other study ID #: TAUL
• Secondary ID: 2009-016017-24
• Status: Completed
• Phase: Phase 2
• First received: September 23, 2014
• Last updated: December 5, 2017
• Start date: April 2010
• Est. completion date: April 30, 2017

Study information

• Verified date: December 2017
• Source: Mario Negri Institute for Pharmacological Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 168
• Est. completion date: April 30, 2017
• Est. primary completion date: April 30, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leiomyosarcoma

Intervention

Drug:
• gemcitabine + docetaxel

• trabectedin

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo	Alessandria
Italy	Centro di Riferimento Oncologico	Aviano	Pordenone
Italy	Azienda Ospedaliera Spedali Civili di Brescia	Brescia
Italy	Presidio Ospedaliero Senatore Antonio Perrino	Brindisi
Italy	Fondazione del Piemonte per l'Oncologia	Candiolo	Turin
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	Milano
Italy	Azienda ULSS 13 Regione Veneto, Ospedale di Mirano	Mirano	Venice
Italy	Azienda Ospedaliera San Gerardo	Monza
Italy	Istituto Nazionale Tumori - Fondazione Pascale	Napoli
Italy	Ospedale Sacro Cuore Don Calabria	Negrar	Verona
Italy	Azienda Ospedaliero Universitaria Maggiore della Carità	Novara
Italy	Istituto Oncologico Veneto	Padova
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	Roma	RM
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

Sponsors (2)

Lead Sponsor	Collaborator
Mario Negri Institute for Pharmacological Research	PharmaMar

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	progression free survival	Time from inclusion into the study to progression or death whichever comes first	24 months
Other	Overall survival	time from inclusion into the study to death from any cause	24 months
Other	safety profile	Number of Patients with Serious and Non-Serious Adverse Events	up to 30 days after the end of treatments
Primary	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	best response rate	response rate according to RECIST v1.0 criteria	within 6 months