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
Inclusion 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