continuing vs intermittent trabectedin in patients with advanced soft tissue sarcoma

Conditions: Soft Tissue Sarcoma; Uterine Sarcoma

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

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 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