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.
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
  Purpose

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

Condition Intervention Phase
Soft Tissue Sarcoma
Uterine Sarcoma
Drug: Trabectedin
Other: Drug: holiday
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Centre Oscar Lambret:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 50
Study Start Date: February 2011
Estimated Study Completion Date: February 2017
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Continuation of Trabectedin 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.
"Intermittent/holiday" therapy 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.

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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01303094

Contacts
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

Locations
France
Saint-Jacques Hospital Active, not recruiting
Besancon, France, 25 000
Institut Bergonié Active, not recruiting
Bordeaux, France, 33076
Centre François Baclesse Active, not recruiting
Caen, France, 14076
Centre Jean Perrin Active, not recruiting
Clermont Ferrand, France, 63011
Centre Georges François Leclerc Active, not recruiting
Dijon, France, 21079
Centre Oscar Lambret Active, not recruiting
Lille, France, 59020
Centre Léon Bérard Active, not recruiting
Lyon, France, 69008
Léon Bérard Center Recruiting
Lyon, France, 69 008
Contact: Isabelle RAY COQUART, MD    +33 (0)4.78.78.28.88    blay@lyon.fnclcc.fr   
Principal Investigator: Isabelle RAY COQUART, MD PhD         
Sub-Investigator: Jean Yves BLAY, MD PhD         
Sub-Investigator: Pierre BIRON, MD         
Sub-Investigator: Marie GHELGHOUM, MD         
Sub-Investigator: Pierre HEUDEL, MD         
Sub-Investigator: Philippe CASSIER, MD         
Sub-Investigator: Olfa DERBEL, MD         
CHU Timone Adultes Active, not recruiting
Marseille, France, 13385
Paoli Calmette Institute Active, not recruiting
Marseille, France, 13 273
Centre Antoine Lacassagne Active, not recruiting
Nice, France, 06189
Institut Curie Active, not recruiting
Paris, France, 75005
Tenon Hospital Withdrawn
Paris, France, 75 020
Centre Henri Becquerel Active, not recruiting
Rouen, France, 76038
Centre René Huguenin Active, not recruiting
St Cloud, France, 92210
Centre René Gauducheau Withdrawn
St Herblain, France, 77805
Institut Claudius Regaud Active, not recruiting
Toulouse, France, 31052
Institut Gustave Roussy Active, not recruiting
Villejuif, France, 94805
Sponsors and Collaborators
Centre Oscar Lambret
Groupe Sarcome Français
Groupe d’études des Tumeurs Osseuses
Investigators
Principal Investigator: Nicolas PENEL, MD, PhD Centre Oscar Lambret
  More Information

No publications provided

Responsible Party: Centre Oscar Lambret
ClinicalTrials.gov Identifier: NCT01303094     History of Changes
Other Study ID Numbers: T-DIS-1001
Study First Received: February 23, 2011
Last Updated: March 6, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Trabectedin
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 21, 2014