Clinical Trial: Efficacy Study on Trabectedin in Retroperitoneal Leiomyosarcoma and Well Differentiated/Dedifferentiated Liposarcoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase II Study on Trabectedin in Advanced Retroperitoneal Leiomyosarcoma and Well Differentiated/Dedifferentiated Liposarcoma

Brief Summary:

This is an Italian, multicentre, single arm, phase II study, with an intra-patient comparison end point. This study aims at confirming the activity of the drug trabectedin as second/further line treatment in retroperitoneal leiomyosarcoma and well differentiated/dedifferentiated liposarcoma expressed in terms of slowing down tumour growth.

Another objective is to investigate this peculiar benefit of trabectedin in typical retroperitoneal sarcomas may be exploited to help multidisciplinary clinical decision-making in the management of retroperitoneal sarcomas


Detailed Summary:

Retroperitoneal soft-tissue sarcomas (R-STSs) are rare neoplasms, accounting for 10% to 15% of Soft Tissue Sarcomas (STSs), which represent 1-3% of all cancers. They may show different histological types, but the predominant ones in the retroperitoneal region are: leiomyosarcoma, liposarcoma. The most commonly encountered in the retroperitoneum is the well differentiated/dedifferentiated liposarcoma.

First-line chemotherapy usually consists of doxorubicin and/or ifosfamide. These two drugs are the most active agents in adult STSs, with a dose-response relationship and response rates between 20% and 50%. However, the sarcoma community is currently doubtful as to the activity of ifosfamide in the subgroup of leiomyosarcomas.

Trabectedin has been found to be mainly active in leiomyosarcoma and liposarcoma and is approved by European Medicines Agency (EMA) as second-line chemotherapy for STSs. Although the response rate observed in pre-registration studies did not exceed 10%, trabectedin provided disease control, with progression arrest rates exceeding 50% and Progression Free Survival (PFS) rates exceeding 20% at 6 months.

Since so far no phase II studies tested the activity of trabectedin in retroperitoneal sarcomas, this is the specific aim of this study.

Target population: Patients with previously treated, histologically confirmed, retroperitoneal leiomyosarcoma and well differentiated/dedifferentiated liposarcoma. Patients may be either unamenable to surgery or amenable but in whom the addition of medical treatment is considered clinically advisable.

Translational studies will be performed, with the aim of characterising the tumour biological features associated with differe
Sponsor: Italian Sarcoma Group

Current Primary Outcome: Growth Modulation Rate [ Time Frame: From date of randomization until progressive disease, assessed up to 48 months ]

The primary end point of the study will be the proportion of responders to trabectedin, based on the ratio, in each single patient, between PFS under trabectedin (PFS) and time to progression after previous chemotherapy treatment (TTP1).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Objective response (OR) in the overall sample [ Time Frame: From date of randomization until progressive disease, assessed up to 48 months ]
  • Pathological tumour response in the two eligible histological types, in patients undergoing surgery after treatment [ Time Frame: From date of randomization until the best tumour dimensional response, assessed up to 48 months ]
  • PFS and OR in the two eligible histological types [ Time Frame: From date of randomization until progressive disease, assessed up to 48 months ]
  • PFS in patients who undergo surgery after, or during, medical therapy and those who do not [ Time Frame: From date of randomization until progressive disease, assessed up to 48 months ]
  • Number of patients with grade>=3 adverse drug reactions, number of serious adverse events related to study drug and number of patients who will experience at least one serious adverse event [ Time Frame: From date of randomization until progressive disease, assessed up to 48 months ]
  • Efficacy of trabectedin in reducing cancer related pain [ Time Frame: From date of randomization until progressive disease, assessed up to 48 months ]
    All patients will be administered a standardized questionnaire evaluating cancer related pain and use of antalgic medication.


Original Secondary Outcome: Same as current

Information By: Italian Sarcoma Group

Dates:
Date Received: September 5, 2014
Date Started: March 2014
Date Completion: October 2020
Last Updated: March 17, 2017
Last Verified: March 2017