Clinical trial NCT02249702: Activity of Trabectedin or Gemcitabine + Docetaxel in Uterine Leiomyosarcoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leiomyosarcoma
Keywords: trabectedin
uterine leiomyosarcoma
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
Collaborators: name: PharmaMar
First posted: 2014-09-25
Enrollment: 168
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: progression free rate at 6-month
timeFrame: 6-month
Secondary outcomes:
measure: best response rate
timeFrame: within 6 months
Other outcomes:
measure: progression free survival
timeFrame: 24 months
measure: Overall survival
timeFrame: 24 months
measure: safety profile
timeFrame: up to 30 days after the end of treatments
Locations:
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico
state: Pordenone
city: Roma
country: Italy
facility: Policlinico Umberto I
state: RM
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l'Oncologia
state: Turin
city: Mirano
country: Italy
facility: Azienda ULSS 13 Regione Veneto, Ospedale di Mirano
state: Venice
city: Negrar
country: Italy
facility: Ospedale Sacro Cuore Don Calabria
state: Verona
city: Alessandria
country: Italy
facility: Azienda Ospedaliera Nazionale SS. Antonio e Biagio e C. Arrigo
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
city: Brindisi
country: Italy
facility: Presidio Ospedaliero Senatore Antonio Perrino
city: Catania
country: Italy
facility: Azienda Ospedaliera per l'Emergenza Cannizzaro
city: Como
country: Italy
facility: Ospedale Sant'Anna
city: Cuneo
country: Italy
facility: Azienda Ospedaliera S. Croce e Carle
city: Genoa
country: Italy
facility: Azienda Ospedaliera Universitaria San Martino - IST
city: Genova
country: Italy
facility: Ente Ospedaliero Ospedali Galliera
city: Lucca
country: Italy
facility: Azienda USL 2 Toscana - Nuovo Ospedale San Luca
city: Milano
country: Italy
facility: Istituto Nazionale dei Tumori di Milano
city: Milan
country: Italy
facility: Istituto Clinico Humanitas
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia
city: Milan
country: Italy
facility: Istituto Nazionale dei Tumori di Milano
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori - Fondazione Pascale
city: Novara
country: Italy
facility: Azienda Ospedaliero Universitaria Maggiore della Carità
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Palermo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria di Parma
city: Pavia
country: Italy
facility: Policlinico San Matteo
city: Pisa
country: Italy
facility: Azienda Ospadaliero-Universitaria Pisana
city: Potenza
country: Italy
facility: Azienda Ospedaliera Regionale San Carlo
city: Reggio Emilia
country: Italy
facility: Azienda Ospedaliera Arcispedale S. Maria Nuova
city: Roma
country: Italy
facility: Ospedale San Giovanni Calibita Fatebenefratelli
city: Roma
country: Italy
facility: Policlinico Umberto I - Università Sapienza
city: Rome
country: Italy
facility: Policlinco Universitario Agostino Gemelli
city: Torino
country: Italy
facility: Azienda Ospedaliera Ordine Mauriziano
city: Torino
country: Italy
facility: Azienda Ospedaliero-Universitaria di Torino - Presidio Sant'Anna
city: Torino
country: Italy
facility: Presidio Sanitario Gradenigo
Study officials:
affiliation: Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
name: Angiolo Gadducci, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliera Alessandria, Italy
name: Federica Grosso, MD
role: PRINCIPAL_INVESTIGATOR
References: