NCT01876043

Efficacy and Safety of Plitidepsin in Patients With Advanced Unresectable or Metastatic, Relapsed/Refractory, Dedifferentiated Liposarcoma (DLPS): an Exploratory Phase II Multicenter Trial

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Institut Bergonié · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Liposarcomas are soft tissue sarcomas most frequent. We distinguish three subtypes on the basis of their histological and cytogenetic characteristics: well-differentiated liposarcoma / dedifferentiated, myxoid liposarcoma and / or round cell liposarcoma and pleomorphic. Dedifferentiated liposarcomas (LDD) represent 20% of liposarcomas and are characterized by well-differentiated component associated with a contingent sarcomatous differentiation and fat-usually high grade. The LDD are most often rétropértionéal seat. Thus, their development is very long asymptomatic. At diagnosis, tumor volume is often very important making surgical removal impossible in a high proportion of cases. Operable tumors have also a risk of local recurrence by about 50% and about 20% metastatic. Chemotherapy is the only treatment of these advanced forms. However, the currently available drugs (adriamycin, ifosfamide) have only very limited effectiveness. Progression-free survival of patients does not exceed 2 months. The LDD is characterized cytogenetically by the constant presence of two amplicons (1p32 and 6q23) respectively targeting genes MAP3K5 and JUN. These two genes encode proteins involved in the signaling pathway Jun N-terminal kinase (JNK). Activation of JNK is involved in the loss of adipose differentiation and tumor aggressiveness of LDD. The plitidepsin is a drug capable of inducing apoptosis of tumor cells carrying a functional activation of the JNK pathway. This drug has such a pro-apoptotic and anti-proliferative in vitro models of LDD. plitidepsin could represent the treatment of choice for patients with advanced LDD. The objective of this study is to evaluate the anti-tumor activity of plitidepsin patients with locally advanced dedifferentiated liposarcomas and / or metastatic.

Conditions

• Adult Patients With Unresectable Locally Advanced or Metastatic, Relapsed/Refractory Dedifferentiated Liposarcoma

Interventions

Type	Name	Description
DRUG	plitidepsin	Patients received plitidepsin as an i.v. 3-h infusion of 5 mg/m2/day on days 1 and 15 every 4 weeks. Patients discontinued plitidepsin if one of the following occurred: consent withdrawal, unacceptable toxicity, disease progression (RECIST v1.1), intercurrent illness or investigator's decision. Single-arm phase II clinical trial based on a two-stage optimal Simon's design with 37 evaluable patients (first stage: 17 patients) used to distinguish a favorable true non-progression rate of 40% from a null rate of 20% (90% power and 10% type I error). * Stage 1(17 participants): if \<=3 non-progressions at 3 months, the study was stopped early. Otherwise, the second group of 20 participants was recruited. * Stage 2 (37 participants): if \>= 11 non-progressions, Aplidin was considered promising.

Timeline

• Start date: 2012-02-01
• Primary completion: 2015-04-01
• Completion: 2015-04-01
• First posted: 2013-06-12
• Last updated: 2021-01-25
• Results posted: 2019-11-12

Locations

6 sites across 1 country: France