Continuing vs Intermittent Trabectedin in Patients With Advanced Soft Tissue Sarcoma

Soft Tissue Sarcoma Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01303094
• Other study ID #: T-DIS-1001
• Status: Completed
• Phase: Phase 2
• Start date: February 2011
• Est. completion date: August 9, 2018

Study information

• Verified date: May 2019
• Source: Centre Oscar Lambret
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: August 9, 2018
• Est. primary completion date: May 16, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Sarcoma
• Soft Tissue Sarcoma
• Uterine Sarcoma

Intervention

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.

Locations

Country	Name	City	State
France	Saint-Jacques Hospital	Besancon
France	Institut Bergonié	Bordeaux
France	Centre François Baclesse	Caen
France	Centre Jean Perrin	Clermont Ferrand
France	Centre Georges François Leclerc	Dijon
France	Centre Oscar Lambret	Lille
France	Centre Léon Bérard	Lyon
France	Léon Bérard Center	Lyon
France	CHU Timone Adultes	Marseille
France	Paoli Calmette Institute	Marseille
France	Centre Antoine Lacassagne	Nice
France	Institut Curie	Paris
France	Centre Henri Becquerel	Rouen
France	Centre René Huguenin	St Cloud
France	Institut Claudius Regaud	Toulouse
France	Institut Gustave Roussy	Villejuif

Sponsors (3)

Lead Sponsor	Collaborator
Centre Oscar Lambret	French Sarcoma Group, Study Group of Bone Tumors

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Response rate	stabilisation, complete and partial responses according to RECIST 1.1	6, 12 and 18 weeks after randomization
Secondary	Progression free survival rates	According to RECIST 1.1	12 and 54 weeks after randomization
Secondary	Survival rates		12 and 24 months after randomization
Secondary	Median progression-free and median overall survivals		Up to 5 years after randomization
Secondary	Tolerability - safety	According to NCI-CTC V4.0 scale	Up to 30 days after the last study drg administration
Secondary	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
Secondary	Post-randomization cost of care	Cost of care will be evaluated by macro-costing approach	For one year after randomization
Secondary	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