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

Centre Oscar Lambret

Status and phase

Completed

Phase 2

Conditions

Soft Tissue Sarcoma

Uterine Sarcoma

Treatments

Other: Drug: holiday

Drug: Trabectedin

Study type

Interventional

Funder types

Other

Identifiers

NCT01303094

T-DIS-1001

Details and patient eligibility

About

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

Full 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

Enrollment

53 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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