Activity of Trabectedin or Gemcitabine + Docetaxel in Uterine Leiomyosarcoma

Phase 2

Completed

• Conditions: Leiomyosarcoma
• Interventions: Drug: gemcitabine + docetaxel; Drug: trabectedin

• Registration Number: NCT02249702
• Lead Sponsor: Mario Negri Institute for Pharmacological Research

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-04
• Study First Submitted: 2014-09-23
• Study First Submitted QC: 2014-09-23
• Study First Posted: 2014-09-25
• Primary Completion: 2017-04-30
• Study Completion: 2017-04-30
• Status Verified: 2017-12
• Last Update Submitted: 2017-12-05
• Last Update Posted: 2017-12-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 168

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
gemcitabine + docetaxel	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.
Trabectedin	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
best response rate	within 6 months	response rate according to RECIST v1.0 criteria

Trial Locations

Locations (33)

Policlinico Umberto I; 🇮🇹 Roma, RM, Italy

Ospedale Sant'Anna; 🇮🇹 Como, Italy

Azienda Ospedaliera S. Croce e Carle; 🇮🇹 Cuneo, Italy

Ente Ospedaliero Ospedali Galliera; 🇮🇹 Genova, Italy

Azienda Ospedaliera San Gerardo; 🇮🇹 Monza, Italy

Istituto Oncologico Veneto; 🇮🇹 Padova, Italy

Policlinico San Matteo; 🇮🇹 Pavia, Italy

Azienda Ospedaliera Regionale San Carlo; 🇮🇹 Potenza, Italy

Ospedale San Giovanni Calibita Fatebenefratelli; 🇮🇹 Roma, Italy

Azienda Ospedaliera Arcispedale S. Maria Nuova; 🇮🇹 Reggio Emilia, Italy

Policlinico Umberto I - Università Sapienza; 🇮🇹 Roma, Italy

Azienda Ospedaliera Ordine Mauriziano; 🇮🇹 Torino, Italy

Centro di Riferimento Oncologico; 🇮🇹 Aviano, Pordenone, Italy

Ospedale Sacro Cuore Don Calabria; 🇮🇹 Negrar, Verona, Italy

Fondazione del Piemonte per l'Oncologia; 🇮🇹 Candiolo, Turin, Italy

Azienda ULSS 13 Regione Veneto, Ospedale di Mirano; 🇮🇹 Mirano, Venice, 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

Azienda Ospedaliera Universitaria San Martino - IST; 🇮🇹 Genoa, Italy

Azienda USL 2 Toscana - Nuovo Ospedale San Luca; 🇮🇹 Lucca, Italy

Istituto Nazionale dei Tumori di Milano; 🇮🇹 Milan, Italy

Istituto Clinico Humanitas; 🇮🇹 Milan, Italy

Istituto Europeo di Oncologia; 🇮🇹 Milan, Italy

Istituto Nazionale Tumori - Fondazione Pascale; 🇮🇹 Napoli, Italy

Azienda Ospedaliero Universitaria Maggiore della Carità; 🇮🇹 Novara, Italy

Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello; 🇮🇹 Palermo, Italy

Azienda Ospedaliero-Universitaria di Parma; 🇮🇹 Parma, Italy

Azienda Ospadaliero-Universitaria Pisana; 🇮🇹 Pisa, Italy

Policlinco Universitario Agostino Gemelli; 🇮🇹 Rome, Italy

Azienda Ospedaliero-Universitaria di Torino - Presidio Sant'Anna; 🇮🇹 Torino, Italy

Presidio Sanitario Gradenigo; 🇮🇹 Torino, Italy