NCT02194231

ATREUS - Phase II Study on the Activity of Trabectedin in Patients With Malignant Pleural Mesothelioma (MPM)

ATREUS Trial - A Phase II Study on the Activity of Trabectedin of Pretreated Epithelioid or Biphasic / Sarcomatoid Malignant Pleural Mesothelioma(MPM)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 145 (actual)
• Sponsor: Mario Negri Institute for Pharmacological Research · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether trabectedin is effective in the treatment of malignant pleural mesothelioma (MPM).

Detailed description

There are no approved agents for second-line treatment of MPM in patients who failed first line pemetrexed plus platinum derivatives regimens. Chemotherapy options are limited and include gemcitabine, vinorelbine and other antifolate compounds. The role of second-line chemotherapy is therefore not yet established and second-line patient population is considered suitable for phase II studies with investigational agents. Trabectedin is an originally natural marine product, now obtained by a semisynthetic process, that induces a delay in S phase progression and a blockade in G2 phase of the cell cycle by a mode of action that seems different from that of other DNA-damaging agents (see citations). Although the exact mechanism of action of trabectedin has not been fully elucidated yet, it appears to be unique compared to other anticancer agents (see citations). Trabectedin binds to N2 of guanines in the minor groove of DNA, causing a bending of the minor groove towards the major groove. In the randomised clinical trials in metastatic leiomyosarcoma or liposarcoma and in recurrent platinum-sensitive ovarian cancer, trabectedin is infused at 1.5 mg/m2 as a 24-hour infusion or 1.3 mg/m2 as a 3 hour infusion every 3 weeks (see citations). Balancing efficacy with safety the short infusion is preferable in clinical practice. In soft tissue sarcoma the response rate did not exceed 10%, however, trabectedin has been shown to provide disease control, with progression arrest rates exceeding 50% and progression-free survival rates exceeding 20% at 6 months. In pre-treated ovarian cancer the objective response rate was 30% with a median time to disease progression of 5.7 months. Trabectedin has not been extensively employed in MPM, however in phase I studies, some objective response in heavily pre-treated mesothelioma patients was seen. The present study is aimed at evaluating the activity of trabectedin in MPM patients not candidate for radical surgery. This option is of particular interest due to lack of valid therapeutic options. Translational studies will be performed to identify factors predictive of the activity of trabectedin in MPM.

Conditions

• Malignant Pleural Mesothelioma

Interventions

Type	Name	Description
DRUG	Trabectedin	Patients will receive 1.1 mg/m2 intravenous trabectedin infusion in 5% glucose via central venous catheter over 3 hours every 21 days. Trabectedin infusion will be preceded by 20 mg of intravenous dexamethasone

Timeline

• Start date: 2013-07-01
• Primary completion: 2019-12-12
• Completion: 2019-12-12
• First posted: 2014-07-18
• Last updated: 2020-01-23

Locations

8 sites across 1 country: Italy