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Trabectedin First Line Therapy In Unfit Sarcoma Study

Phase 2
Completed
Conditions
Metastatic and Locally Advanced Soft Tissue Tumor Patients Unfit to Receive
Standard Chemotherapy
Interventions
Registration Number
NCT02066675
Lead Sponsor
Italian Sarcoma Group
Brief Summary

Phase II, non-randomized, two-stage study according to Bryant \& Day The study enroll patients with Metastatic and locally advanced soft tissue sarcoma unfit to receive standard chemotherapy (doxorubicin/epirubicin and/or ifosfamide)

Detailed Description

Soft tissue sarcomas are a group of rare and aggressive disease, comprising more than a hundred different histological subtypes and mainly originating from the embryonic mesoderm. Today, they represent less than 1% of all adult cancers, with an incidence of 3/100000/year and a median age at diagnosis of 65 years. Despite the progress done in the last decade, approximately 50% of STS patients still develop distant metastases within 3 years from the diagnosis and die from their disease. Doxorubicin (or epirubicin) and ifosfamide have been proved to be active in the treatment of STS and they are widely used, alone or in combination, as a first line therapy for locally advanced and metastatic patients. However, the response rate to the combination regimen in non-pretreated patients does not exceed 30-40%, and large randomized clinical trials failed to demonstrate any advantage in survival for the combination compared to single-agent treatment. Trabectedin (Yondelis®) is a marine-derived anticancer agent that has been approved in the European Union as a single agent for the treatment of STS patients after failure of standard chemotherapy (doxorubicin and/or ifosfamide) or for those unsuited to receive these agents. Even if the response rate in soft tissue sarcoma does not exceed 10%, trabectedin can provide a significant clinical benefit, by arresting disease progression in almost 50% of treated patients, with a progression-free survival rate of 20% at 6 months. Trabectedin was found to be particularly active in the treatment of myxoid liposarcoma and uterine leiomyosarcoma, for which better results have been obtained in terms of response rate and survival, suggesting an histotype driven activity. The toxicity profile of trabectedin given as second line therapy has been widely assessed in clinical studies and was largely manageable, with the majority of adverse events being grade 1 or 2 toxicities, generally reversible, dose or time dependent and noncumulative. The good tolerability profile observed in the trials seems to be confirmed also in everyday clinical practice. Conversely, few data are available at the moment about tolerability profile for those patients treated with trabectedin as first line because of medical conditions contraindicating the use of standard agents. The aim of this phase II study is to assess and describe trabectedin toxicity profile in this subset of negatively selected advanced inoperable STS patients.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
24
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TrabectedinTrabectedinTrabectedin administered at the dose of 1.5 mg/mq-1.3 mg/mq a 24-hour continuous infusion via a central venous access, every 3 weeks
Primary Outcome Measures
NameTimeMethod
Progression Free Survival Rate3 Months

The primary end point of this trial is the Progression Free Survival Rate at 3 months Non progression, is defined as Complete Response, Partial Response or Stable Disease according to Response Evaluation Criteria In Solid Tumours v.1.1 criteria.

Secondary Outcome Measures
NameTimeMethod
Objective response rate5 years

Proportion of patients whose best response is either partial response or complete response

Tolerability and intolerable adverse reaction rate.Day21

Intolerable toxicity is defined as every Adverse Events leading to treatment discontinuation or dose-reduction; furthermore, any Adverse Events of at least grade 3 not resolved within 3 weeks of appropriate management should be regarded as an intolerable toxicity event. For haematological toxicity, given that the use of growth factors will be allowed, an intolerable toxicity is defined either as any grade 4 event, or a grade 3 event not resolved with adequate treatment.

Progression free survivalAverage of 5 Months

It's the length of time during and after the treatment of a disease, that a patient lives with the disease but it does not progress

Overall survival18 Months (average)

it's the length of time after the treatment's end that the patient survives

Trial Locations

Locations (16)

Ospedali Riuniti di Bergamo

🇮🇹

Bergamo, BG, Italy

Ospedale Galliera

🇮🇹

Genova, Genovs, Italy

I.R.C.C. - Unit of Medical Oncology

🇮🇹

Candiolo, Torino, Italy

Policlinico Federico II Napoli

🇮🇹

Napoli, Italy

IRCCS Azienda Ospedaliera Universitaria San Martino IST

🇮🇹

Genova, GE, Italy

Ospedale Villa Scassi

🇮🇹

Genova, GE, Italy

Ospedale Misericordia e Dolce" Istituto Toscano Tumori, Azienda USL4

🇮🇹

Prato, PO, Italy

Presidio Sanitario Gradenigo

🇮🇹

Torino, TO, Italy

Istituti Ortopedici Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors

🇮🇹

Bologna, Italy

IST

🇮🇹

Genova, Italy

Ospedale Giaccone

🇮🇹

Palermo, Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST

🇮🇹

Meldola, FC, Italy

Campus Biomedico

🇮🇹

Roma, Italy

A.S.O. "SS Antonio e Biagio e Cesare Arrigo"

🇮🇹

Alessandria, Italy

Ospedale SS. Trinità di Sora

🇮🇹

Frosinone, Italy

Istituto Oncologico Veneto

🇮🇹

Padova, Italy

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