Trabectedin First Line Therapy In Unfit Sarcoma Study (TR1US)

April 9, 2018 updated by: Italian Sarcoma Group

SAFETY AND ACTIVITY OF TRABECTEDIN AS FIRST LINE IN ADVANCED SOFT TISSUE SARCOMA (STS) PATIENTS UNFIT TO RECEIVE STANDARD CHEMOTHERAPY: A PROSPECTIVE PHASE II STUDY WITH CLINICAL AND MOLECULAR CORRELATES

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)

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Alessandria, Italy
        • A.S.O. "SS Antonio e Biagio e Cesare Arrigo"
      • Bologna, Italy, 40136
        • Istituti Ortopedici Rizzoli - Unit of chemotherapy of Muscoloskeletal Tumors
      • Frosinone, Italy
        • Ospedale SS. Trinità di Sora
      • Genova, Italy
        • IST
      • Napoli, Italy
        • Policlinico Federico II Napoli
      • Padova, Italy
        • Istituto Oncologico Veneto
      • Palermo, Italy
        • Ospedale Giaccone
      • Roma, Italy
        • Campus Biomedico
    • BG
      • Bergamo, BG, Italy
        • Ospedali Riuniti di Bergamo
    • FC
      • Meldola, FC, Italy
        • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST
    • GE
      • Genova, GE, Italy
        • IRCCS Azienda Ospedaliera Universitaria San Martino IST
      • Genova, GE, Italy
        • Ospedale Villa Scassi
    • Genovs
      • Genova, Genovs, Italy
        • Ospedale Galliera
    • PO
      • Prato, PO, Italy
        • Ospedale Misericordia e Dolce" Istituto Toscano Tumori, Azienda USL4
    • TO
      • Torino, TO, Italy, 10153
        • Presidio Sanitario Gradenigo
    • Torino
      • Candiolo, Torino, Italy, 10060
        • I.R.C.C. - Unit of Medical Oncology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria

  • Adult patients (≥18 years), who, in the judgment of the clinician, is deemed not suitable to receive an anthracycline and/or ifosfamide based chemotherapy;
  • Pathological diagnosis of soft tissue sarcoma
  • Inoperable, locally advanced or metastatic tumor;
  • Unsuited to receive doxorubicine and ifosfamide: ie stable arrhythmia, previous myocardial infarction; age≥80 years
  • Eastern Cooperative Oncology Group Performance Status 0-2
  • Glomerular filtration rate ≥30 mL per min
  • Adequate hematologic function: Hemoglobin ≥9 g/dL; Absolute neutrophil count ≥1,500/μL, and Platelet count ≥100,000/microliter
  • Creatinine phosphokinase < 2.5 Upper Normal Limit
  • Adequate hepatic function: total bilirubin < Upper Normal Limit, total alkaline phosphatase < 2.5 Upper Normal Limit, or if > 2.5 Upper Normal Limit consider alkaline phosphatase liver fraction or gamma-glutamyltransferase or 5' nucleotidase must be < Transminase <2.5 x Upper Normal Limit, Albumin > 20 g/L.
  • Patient´s written informed consent

Exclusion criteria

  • Prior exposure to Trabectedin
  • Performance status ≥2.
  • Prior treatment with anthracyclines and or ifosfamide.
  • History of other malignancies (except basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission for 5 or more years and judged of negligible potential of relapse.
  • Active viral hepatitis or chronic liver diseases, which in the judgement of the primary investigator represents a clinical contraindication to the therapy.
  • Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within 6 months before enrolment, uncontrolled arterial hypertension or arrhythmias, left ventricular ejection fraction <40%
  • Active major infection.
  • Other serious concomitant illnesses
  • Pregnant subjects or breast feeding, or planning to become pregnant within 6 months after the end of treatment All sexually active female patients with reproductive potential must have a negative pregnancy test (serum or urine) within the 7 days prior to enrollment and must agree to use highly effective contraception during treatment and for 6 months after the end of treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Trabectedin
Trabectedin 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
Each patients will receive intravenous trabectedin (1.5 mg/mq-1.3 mg/mq) over 24 hours every 3 weeks
Other Names:
  • Yondelis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival Rate
Time Frame: 3 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.
3 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tolerability and intolerable adverse reaction rate.
Time Frame: 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.
Day21
Objective response rate
Time Frame: 5 years
Proportion of patients whose best response is either partial response or complete response
5 years
Progression free survival
Time Frame: Average 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
Average of 5 Months
Overall survival
Time Frame: 18 Months (average)
it's the length of time after the treatment's end that the patient survives
18 Months (average)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Federica Grosso, MD, ASO SS Antonio e Biagio e C Arrigo Alessandria, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Actual)

December 31, 2016

Study Completion (Actual)

December 31, 2016

Study Registration Dates

First Submitted

February 13, 2014

First Submitted That Met QC Criteria

February 17, 2014

First Posted (Estimate)

February 19, 2014

Study Record Updates

Last Update Posted (Actual)

April 11, 2018

Last Update Submitted That Met QC Criteria

April 9, 2018

Last Verified

April 1, 2018

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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