Activity of Trabectedin or Gemcitabine + Docetaxel in Uterine Leiomyosarcoma

NCT ID: NCT02249702

Last Updated: 2017-12-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 168 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2017-04-30

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.

Conditions

Leiomyosarcoma

Keywords

trabectedin; uterine leiomyosarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

trabectedin

Intervention Type: DRUG

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.

Group Type: ACTIVE_COMPARATOR

gemcitabine + docetaxel

Intervention Type: DRUG

Interventions

gemcitabine + docetaxel

Intervention Type: DRUG

trabectedin

Intervention Type: DRUG

Other Intervention Names

Gemzar; Taxotere; Yondelis

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

PharmaMar

INDUSTRY

Sponsor Role: collaborator

Mario Negri Institute for Pharmacological Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Angiolo Gadducci, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliero Universitaria Pisana, Pisa, Italy

Federica Grosso, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliera Alessandria, Italy

Locations

Centro di Riferimento Oncologico

Aviano, Pordenone, Italy

Policlinico Umberto I

Roma, RM, 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

Countries

Italy

Other Identifiers

2009-016017-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TAUL

Identifier Type: -

Identifier Source: org_study_id