Continuing vs Intermittent Trabectedin in Patients With Advanced Soft Tissue Sarcoma

• Status: Completed
• Trial end date: 2018-08-09
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre Oscar Lambret
• Collaborators: French Sarcoma Group; Groupe d’études des Tumeurs Osseuses; Groupe Sarcome Français; Study Group of Bone Tumors
• Treatments: Trabectedin

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