Leiomyosarcoma
Conditions
Keywords
trabectedin, uterine leiomyosarcoma
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.
Interventions
DRUGtrabectedin
Sponsors
PharmaMar
Mario Negri Institute for Pharmacological Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| best response rate | within 6 months | response rate according to RECIST v1.0 criteria |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Italy
Outcome results
None listed