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

Primary Purpose

Soft Tissue Sarcoma, Uterine Sarcoma

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Trabectedin
Drug: holiday
Sponsored by
Centre Oscar Lambret
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Soft Tissue Sarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Saint-Jacques Hospital
  • Institut Bergonié
  • Centre François Baclesse
  • Centre Jean Perrin
  • Centre Georges François Leclerc
  • Centre Oscar Lambret
  • Léon Bérard Center
  • Centre Léon Bérard
  • Paoli Calmette Institute
  • CHU Timone Adultes
  • Centre Antoine Lacassagne
  • Institut Curie
  • Centre Henri Becquerel
  • Centre René Huguenin
  • Institut Claudius Regaud
  • Institut Gustave Roussy

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Continuation of Trabectedin

"Drug holiday" therapy

Arm Description

patient receives 6 cycles of trabectedin, then one dose 15 days after the 6th cycle, every 3 weeks until progression/ toxicity

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Response rate
stabilisation, complete and partial responses according to RECIST 1.1
Progression free survival rates
According to RECIST 1.1
Survival rates
Median progression-free and median overall survivals
Tolerability - safety
According to NCI-CTC V4.0 scale
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
Post-randomization cost of care
Cost of care will be evaluated by macro-costing approach
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

Full Information

First Posted
February 23, 2011
Last Updated
May 29, 2019
Sponsor
Centre Oscar Lambret
Collaborators
French Sarcoma Group, Study Group of Bone Tumors
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1. Study Identification

Unique Protocol Identification Number
NCT01303094
Brief Title
Continuing vs Intermittent Trabectedin in Patients With Advanced Soft Tissue Sarcoma
Acronym
T-DIS
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
February 2011 (Actual)
Primary Completion Date
May 16, 2018 (Actual)
Study Completion Date
August 9, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Oscar Lambret
Collaborators
French Sarcoma Group, Study Group of Bone Tumors

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Soft Tissue Sarcoma, Uterine Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
53 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Continuation of Trabectedin
Arm Type
Other
Arm Description
patient receives 6 cycles of trabectedin, then one dose 15 days after the 6th cycle, every 3 weeks until progression/ toxicity
Arm Title
"Drug holiday" therapy
Arm Type
Other
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Trabectedin
Other Intervention Name(s)
Yondelis
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Drug: holiday
Other Intervention Name(s)
No drug
Intervention Description
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.
Primary Outcome Measure Information:
Title
PFS rate 24 weeks after randomization
Description
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.
Time Frame
24 weeks after randomization
Secondary Outcome Measure Information:
Title
Response rate
Description
stabilisation, complete and partial responses according to RECIST 1.1
Time Frame
6, 12 and 18 weeks after randomization
Title
Progression free survival rates
Description
According to RECIST 1.1
Time Frame
12 and 54 weeks after randomization
Title
Survival rates
Time Frame
12 and 24 months after randomization
Title
Median progression-free and median overall survivals
Time Frame
Up to 5 years after randomization
Title
Tolerability - safety
Description
According to NCI-CTC V4.0 scale
Time Frame
Up to 30 days after the last study drg administration
Title
Clinical and biological predictive factors for non progression at the 6th cycle
Description
Collected data at baseline : age, gender, comorbidity, disease history, previous treatment, tumor description, biological parameters
Time Frame
At baseline
Title
Post-randomization cost of care
Description
Cost of care will be evaluated by macro-costing approach
Time Frame
For one year after randomization
Title
Self estimation of general health status
Description
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
Time Frame
For 1 year after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicolas PENEL, MD, PhD
Organizational Affiliation
Centre Oscar Lambret
Official's Role
Principal Investigator
Facility Information:
Facility Name
Saint-Jacques Hospital
City
Besancon
ZIP/Postal Code
25 000
Country
France
Facility Name
Institut Bergonié
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Centre François Baclesse
City
Caen
ZIP/Postal Code
14076
Country
France
Facility Name
Centre Jean Perrin
City
Clermont Ferrand
ZIP/Postal Code
63011
Country
France
Facility Name
Centre Georges François Leclerc
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59020
Country
France
Facility Name
Léon Bérard Center
City
Lyon
ZIP/Postal Code
69 008
Country
France
Facility Name
Centre Léon Bérard
City
Lyon
ZIP/Postal Code
69008
Country
France
Facility Name
Paoli Calmette Institute
City
Marseille
ZIP/Postal Code
13 273
Country
France
Facility Name
CHU Timone Adultes
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Centre Antoine Lacassagne
City
Nice
ZIP/Postal Code
06189
Country
France
Facility Name
Institut Curie
City
Paris
ZIP/Postal Code
75005
Country
France
Facility Name
Centre Henri Becquerel
City
Rouen
ZIP/Postal Code
76038
Country
France
Facility Name
Centre René Huguenin
City
St Cloud
ZIP/Postal Code
92210
Country
France
Facility Name
Institut Claudius Regaud
City
Toulouse
ZIP/Postal Code
31052
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
25680558
Citation
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.
Results Reference
derived

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Continuing vs Intermittent Trabectedin in Patients With Advanced Soft Tissue Sarcoma

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