Continuing vs Intermittent Trabectedin in Patients With Advanced Soft Tissue Sarcoma (T-DIS)

Phase II Randomized Trial to Evaluate Two Strategies: Continuing Versus Intermittent (Drug-holiday) Trabectedin-regimen in Patients With Advanced Soft Tissue Sarcoma Experiencing Response or Stable Disease After the Sixth Cycle

This randomization discontinuation trial will allow for concomitant evaluation of the following:

• Side effects and benefits of immediate continuation of Trabectedin after the sixth cycle
• Side effects and benefits of a drug holiday

Study Overview

• Status: Completed
• Conditions: Soft Tissue Sarcoma; Uterine Sarcoma
• Intervention / Treatment: Drug: Trabectedin; Other: Drug: holiday

Detailed Description

Selection part (220 patients):

Trabectedin (depending on dose reductions : between 1.5 and 1 mg/m²/3 weeks; over 24 hour administration) until progression, intolerance or 6 cycles (according to the SPC of Trabectedin)

Randomized part (50 patients):

After the 6 first cycles, if there is not progression or unacceptable toxicity, the patients will be randomly assigned to continuous or "intermittent/holiday" therapy with CT-scan evaluation every 6 weeks in both arms

• Arm A Continuation of Trabectedin (between 1.5 and 1 mg/m²/3 weeks; over 24 hour administration) until progression or intolerance
• Arm B "Intermittent/holiday" therapy. Rechallenge of Trabectedin will be implemented in the event of progression; in this case administration of Trabectedin will occur until the second progression or intolerance

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Besançon, France, 25 000
    • Saint-Jacques Hospital
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Caen, France, 14076
    • Centre Francois Baclesse
  • Clermont-Ferrand, France, 63011
    • Centre Jean Perrin
  • Dijon, France, 21079
    • Centre Georges François Leclerc
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lyon, France, 69008
    • Centre Leon Berard
  • Lyon, France, 69 008
    • Léon Bérard Center
  • Marseille, France, 13385
    • CHU Timone Adultes
  • Marseille, France, 13 273
    • Paoli Calmette Institute
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Paris, France, 75005
    • Institut Curie
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Saint-Cloud, France, 92210
    • Centre Rene Huguenin
  • Toulouse, France, 31052
    • Institut Claudius Regaud
  • Villejuif, France, 94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (for the selection part):

• Inoperable or metastatic soft tissue sarcoma and/or uterine sarcoma
• Measurable lesions (RECIST 1.1)
• Performance status ≤ 2
• Age ≥ 18
• Normal hematological parameters (polynuclear neutrophils ≥ 1500, hemoglobin level ≥ 9 g/dl, platelets counts ≥ 100,000)
• Adequate biological parameters :
• Adequate hepatic function (bilirubin ≤ ULN , SGPT/ALT and SGOT/AST ≤ 2.5 x ULN)
• Alkaline phosphatases ≤ 2.5 x ULN, If Alkaline phosphatases ≥ 2.5 ULN, hepatic isoenzymes 5-nucleotidases or GGT tests must be performed; hepatic isoenzymes 5- nucleotidases and/or GGT must be within the normal range
• Albumin ≥ 25 g/L
• Adequate renal function : Serum creatinine ≤ 1.5 x ULN
• Creatine phosphokinase ≤ 2.5 x ULN
• Adequate central venous access
• Pregnant or lactating women or men of reproductive potential must use effective contraceptive methods
• Patient covered by government health insurance
• Information sheet given to the patient (Patient information sheet 1)

Exclusion Criteria (for the selection part):

• Patients that have received more than one regimen of chemotherapy for metastatic or inoperable soft tissue or uterine sarcoma, after the failure/intolerance of doxorubicin and ifosfamide. Maintenance treatment does not count as treatment line
• The following histological subtypes : GIST, rhabdomyosarcoma, aggressive fibromatosis, desmoïd tumour, PNET, carcinosarcoma, and all bone sarcomas
• Single tumour in an irradiated region
• Other malignant tumour over the past five years (except basal cell carcinoma or cervical carcinoma in situ adequately treated)
• Currently active bacterial or fungus infection (> grade 2 CTC [CTCAE] Version 4.02). Known HIV1, HIV2, hepatitis B or hepatitis C infections
• Presence of known leptomeningeal or brain metastasis
• Patients unable to receive corticotherapy
• Any circumstance that could jeopardise compliance or proper follow-up during the trial
• Pregnant or nursing women

Inclusion Criteria (for the randomized part):

• Patient registered in the selection part
• Stable tumour or objective response (CR + PR) after 6 Trabectedin (Yondelis®) cycles, according to local assessment
• Available copies of thoraco-abdominal and pelvic scan performed prior to the first cycle and after the sixth cycle
• Performance status ≤ 2
• Patients receiving at least 1 mg/m²/3 weeks of Trabectedin at the time of the sixth cycle
• Normal hematological parameters (polynuclear neutrophils ≥ 1500, hemoglobin level ≥ 9 g/dl, platelets counts ≥ 100,000)
• Adequate biological parameters :
• Adequate hepatic function (bilirubin ≤ ULN , SGPT/ALT and SGOT/AST ≤ 2.5 x ULN)
• Alkaline phosphatases ≤ 2.5 x ULN, If Alkaline phosphatases ≥ 2.5 ULN, hepatic isoenzymes 5-nucleotidases or GGT tests must be performed; hepatic isoenzymes 5- nucleotidases and/or GGT must be within the normal range
• Albumin ≥ 25 g/L
• Adequate renal function : Serum creatinine ≤ 1.5 x ULN
• Creatine phosphokinase (CPK) ≤ 2.5 x ULN
• Adequate central venous access
• Pregnant or lactating women or men of reproductive potential must use effective contraceptive methods
• Informed consent form signed by the patient or the patient's legal representative (patient information sheet 2 and informed consent)

Exclusion Criteria (for the randomized part):

• Tumour progression (according to RECIST 1.1) during the first six Yondelis cycles
• Non-availability of baseline scans prior to the first cycle and following the sixth cycle
• Currently active bacterial or fungus infection (> grade 2 CTC [CTCAE] Version 4.02). Known HIV1, HIV2, hepatitis B or hepatitis C infections
• Presence of known leptomeningeal or brain metastasis
• Creatinine clearance less than 30 ml/min
• Patients unable to receive corticotherapy
• Any circumstance that could jeopardise compliance or proper follow-up during the trial
• Pregnant or nursing women
• Hypersensitivity to Trabectedin or any excipient in prior cycles

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Continuation of Trabectedin; patient receives 6 cycles of trabectedin, then one dose 15 days after the 6th cycle, every 3 weeks until progression/ toxicity	Drug: Trabectedin; Trabectedin will be administered without drug holiday in Arm A until unacceptable toxicity, progressive disease or patient decision. The treatment beyond disease progression and in case of intolerance will be decided according to investigator discretion. In case of progression after drug discontinuation by patient decision, a re-challenge of Trabectedin is possible.; Other Names: Yondelis
Other: "Drug holiday" therapy; patient receives 6 cycles of trabectedin, then one dose 15 days after the 6th cycle and he stops the drug until progression and re-challenge	Other: Drug: holiday; A drug-holiday will start after the 6th cycle until disease progression, and then Trabectedin will be re-challenged. Trabectedin will be administered until unacceptable toxicity, second evidence of progressive disease or patient decision.; Other Names: No drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS rate 24 weeks after randomization	In each arms among non progressive patients after the 6 first cycles of Trabectedin : occurrence of progression or death 24 weeks after the date of randomization. Intention to treat analysis. Centralised radiological review.	24 weeks after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	stabilisation, complete and partial responses according to RECIST 1.1	6, 12 and 18 weeks after randomization
Progression free survival rates	According to RECIST 1.1	12 and 54 weeks after randomization
Survival rates		12 and 24 months after randomization
Median progression-free and median overall survivals		Up to 5 years after randomization
Tolerability - safety	According to NCI-CTC V4.0 scale	Up to 30 days after the last study drg administration
Clinical and biological predictive factors for non progression at the 6th cycle	Collected data at baseline : age, gender, comorbidity, disease history, previous treatment, tumor description, biological parameters	At baseline
Post-randomization cost of care	Cost of care will be evaluated by macro-costing approach	For one year after randomization
Self estimation of general health status	Evaluation every 6 weeks by 100-mm-long horizontal visual analog scale (VAS) that ranged from worst imaginable health (as bad as death, 0) to perfect health	For 1 year after randomization

Collaborators and Investigators

• Sponsor: Centre Oscar Lambret
• Collaborators: French Sarcoma Group; Study Group of Bone Tumors
• Investigators: Principal Investigator: Nicolas PENEL, MD, PhD, Centre Oscar Lambret

Publications and helpful links

General Publications

• Le Cesne A, Blay JY, Domont J, Tresch-Bruneel E, Chevreau C, Bertucci F, Delcambre C, Saada-Bouzid E, Piperno-Neumann S, Bay JO, Mir O, Ray-Coquard I, Ryckewaert T, Valentin T, Isambert N, Italiano A, Clisant S, Penel N. Interruption versus continuation of trabectedin in patients with soft-tissue sarcoma (T-DIS): a randomised phase 2 trial. Lancet Oncol. 2015 Mar;16(3):312-9. doi: 10.1016/S1470-2045(15)70031-8. Epub 2015 Feb 11.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2011
• Primary Completion (Actual): May 16, 2018
• Study Completion (Actual): August 9, 2018

Study Registration Dates

• First Submitted: February 23, 2011
• First Submitted That Met QC Criteria: February 23, 2011
• First Posted (Estimated): February 24, 2011

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Sarcoma; Delivery of Health Care; Health Care Quality, Access, and Evaluation; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dioxoles; Tetrahydroisoquinolines; Isoquinolines; Attitude to Health; Treatment Adherence and Compliance; Trabectedin; Treatment Interruption
• Other Study ID Numbers: T-DIS-1001; 2010-022613-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO