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Continuing vs Intermittent Trabectedin-regimen in Patients With Advanced Soft Tissue Sarcoma Experiencing Response or Stable Disease After the 6th Cycle (T-DIS)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified August 2012 by Centre Oscar Lambret
Sponsor:
Collaborators:
Groupe Sarcome Français
Groupe d’études des Tumeurs Osseuses
Information provided by (Responsible Party):
Centre Oscar Lambret
ClinicalTrials.gov Identifier:
NCT01303094
First received: February 23, 2011
Last updated: March 6, 2014
Last verified: August 2012

February 23, 2011
March 6, 2014
February 2011
December 2013   (final data collection date for primary outcome measure)
PFS rate 24 weeks after randomization [ Time Frame: 24 weeks after randomization ] [ Designated as safety issue: No ]
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.
Same as current
Complete list of historical versions of study NCT01303094 on ClinicalTrials.gov Archive Site
  • Response rate [ Time Frame: 6, 12 and 18 weeks after randomization ] [ Designated as safety issue: No ]
    stabilisation, complete and partial responses according to RECIST 1.1
  • Progression free survival rates [ Time Frame: 12 and 54 weeks after randomization ] [ Designated as safety issue: No ]
    According to RECIST 1.1
  • Survival rates [ Time Frame: 12 and 24 months after randomization ] [ Designated as safety issue: No ]
  • Median progression-free and median overall survivals [ Time Frame: Up to 5 years after randomization ] [ Designated as safety issue: No ]
  • Tolerability [ Time Frame: Up to 30 days after the last study drg administration ] [ Designated as safety issue: Yes ]
    According to NCI-CTC V4.0 scale
  • Clinical and biological predictive factors for non progression at the 6th cycle [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    Collected data at baseline : age, gender, comorbidity, disease history, previous treatment, tumor description, biological parameters
  • Post-randomization cost of care [ Time Frame: For one year after randomization ] [ Designated as safety issue: No ]
    Cost of care will be evaluated by macro-costing approach
  • Self estimation of general health status [ Time Frame: For 1 year after randomization ] [ Designated as safety issue: No ]
    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
  • Response rate [ Time Frame: 6, 12 and 18 weeks after randomization ] [ Designated as safety issue: No ]
    stabilisation, complete and partial responses according to RECIST 1.1
  • Progression free survival rates [ Time Frame: 12 and 54 weeks after randomization ] [ Designated as safety issue: No ]
    According to RECIST 1.1
  • Survival rates [ Time Frame: 12 and 24 months after randomization ] [ Designated as safety issue: No ]
  • Median progression-free and median overall survivals [ Time Frame: from the randomization date and from the first cycle date ] [ Designated as safety issue: No ]
  • Tolerability [ Time Frame: Throughout the randomized part ] [ Designated as safety issue: Yes ]
    According to NCI-CTC V4.0 scale
  • Clinical and biological predictive factors for non progression at the 6th cycle [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    Collected data at baseline : age, gender, comorbidity, disease history, previous treatment, tumor description, biological parameters
  • Post-randomization cost of care [ Time Frame: For one year after randomization ] [ Designated as safety issue: No ]
    Cost of care will be evaluated by macro-costing approach
  • Self estimation of general health status [ Time Frame: For 1 year after randomization ] [ Designated as safety issue: No ]
    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
Not Provided
Not Provided
 
Continuing vs Intermittent Trabectedin-regimen in Patients With Advanced Soft Tissue Sarcoma Experiencing Response or Stable Disease After the 6th Cycle
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

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
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Soft Tissue Sarcoma
  • Uterine Sarcoma
  • 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: 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.
  • Continuation of Trabectedin
    Intervention: Drug: Trabectedin
  • "Intermittent/holiday" therapy
    Intervention: Other: Drug: holiday
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
50
February 2017
December 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Nicolas PENEL, MD, PhD 03.20.29.59.20 n-penel@o-lambret.fr
Contact: Yvette VENDEL, CRA 03.20.29.59.40 y-vendel@o-lambret.fr
France
 
NCT01303094
T-DIS-1001
Yes
Centre Oscar Lambret
Centre Oscar Lambret
  • Groupe Sarcome Français
  • Groupe d’études des Tumeurs Osseuses
Principal Investigator: Nicolas PENEL, MD, PhD Centre Oscar Lambret
Centre Oscar Lambret
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP