TAUL: Activity of Trabectedin or Gemcitabine + Docetaxel in Uterine Leiomyosarcoma

Sponsor

Mario Negri Institute for Pharmacological Research (Other)

Overall Status

Completed

CT.gov ID

NCT02249702

Collaborator

PharmaMar (Industry)

168

Enrollment

Locations

Arms

Duration (Months)

4.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leiomyosarcoma	Drug: gemcitabine + docetaxel Drug: trabectedin	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

168 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 :

Apr 1, 2010

Actual Primary Completion Date :

Apr 30, 2017

Actual Study Completion Date :

Apr 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Trabectedin 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.	Drug: trabectedin Other Names: 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 Other Names: Gemzar Taxotere

Arm

Intervention/Treatment

Experimental: Trabectedin

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.

Drug: trabectedin

Other Names:

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

Other Names:

Gemzar

Taxotere

Outcome Measures

Primary Outcome Measures

progression free rate at 6-month [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.

Secondary Outcome Measures

best response rate [within 6 months]
response rate according to RECIST v1.0 criteria

Other Outcome Measures

progression free survival [24 months]
Time from inclusion into the study to progression or death whichever comes first
Overall survival [24 months]
time from inclusion into the study to death from any cause
safety profile [up to 30 days after the end of treatments]
Number of Patients with Serious and Non-Serious Adverse Events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centro di Riferimento Oncologico	Aviano	Pordenone	Italy
2	Policlinico Umberto I	Roma	RM	Italy	00186
3	Fondazione del Piemonte per l'Oncologia	Candiolo	Turin	Italy
4	Azienda ULSS 13 Regione Veneto, Ospedale di Mirano	Mirano	Venice	Italy
5	Ospedale Sacro Cuore Don Calabria	Negrar	Verona	Italy
6	Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo	Alessandria		Italy
7	Azienda Ospedaliera Spedali Civili di Brescia	Brescia		Italy
8	Presidio Ospedaliero Senatore Antonio Perrino	Brindisi		Italy
9	Azienda Ospedaliera per l'Emergenza Cannizzaro	Catania		Italy
10	Ospedale Sant'Anna	Como		Italy
11	Azienda Ospedaliera S. Croce e Carle	Cuneo		Italy
12	Azienda Ospedaliera Universitaria San Martino - IST	Genoa		Italy
13	Ente Ospedaliero Ospedali Galliera	Genova		Italy
14	Azienda USL 2 Toscana - Nuovo Ospedale San Luca	Lucca		Italy
15	Istituto Nazionale dei Tumori di Milano	Milano		Italy
16	Istituto Clinico Humanitas	Milan		Italy
17	Istituto Europeo di Oncologia	Milan		Italy
18	Istituto Nazionale dei Tumori di Milano	Milan		Italy
19	Azienda Ospedaliera San Gerardo	Monza		Italy
20	Istituto Nazionale Tumori - Fondazione Pascale	Napoli		Italy
21	Azienda Ospedaliero Universitaria Maggiore della Carità	Novara		Italy
22	Istituto Oncologico Veneto	Padova		Italy
23	Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello	Palermo		Italy
24	Azienda Ospedaliero-Universitaria di Parma	Parma		Italy
25	Policlinico San Matteo	Pavia		Italy
26	Azienda Ospadaliero-Universitaria Pisana	Pisa		Italy
27	Azienda Ospedaliera Regionale San Carlo	Potenza		Italy
28	Azienda Ospedaliera Arcispedale S. Maria Nuova	Reggio Emilia		Italy
29	Ospedale San Giovanni Calibita Fatebenefratelli	Roma		Italy
30	Policlinico Umberto I - Università Sapienza	Roma		Italy
31	Policlinco Universitario Agostino Gemelli	Rome		Italy
32	Azienda Ospedaliera Ordine Mauriziano	Torino		Italy
33	Azienda Ospedaliero-Universitaria di Torino - Presidio Sant'Anna	Torino		Italy
34	Presidio Sanitario Gradenigo	Torino		Italy

Sponsors and Collaborators

Mario Negri Institute for Pharmacological Research
PharmaMar

Investigators

Principal Investigator: Angiolo Gadducci, MD, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
Principal Investigator: Federica Grosso, MD, Azienda Ospedaliera Alessandria, Italy