Patient case: 38-year-old male with Liposarcoma. Genetic variant: CDK4 Amplification. Other conditions: GERD.

Clinical trial: Continuing vs Intermittent Trabectedin in Patients With Advanced Soft Tissue 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

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: 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

Relevance to patient case: not relevant