Hyper-Thermia Enhanced Anti-tumor Efficacy of Trabectedin

Trabectedin Combined With Regional Hyperthermia as Second Line Treatment for Adult Patients With Advanced Soft-tissue Sarcoma

This trial compares trabectedin alone to trabectedin in combination with regional hyperthermia in patients with high-risk soft tissue sarcoma. The study is designed to demonstrate a significant benefit for sarcoma-therapy by adding regional hyperthermia.

Inclusion Criteria:

• Age > 18 years
• Histologically confirmed STS (primary or recurrent), except: Ewing sarcoma, osteosarcoma, skeletal chondrosarcoma (extraskeletal chondrosacomas are included), GIST, dermatofibrosarcoma protuberans, malignant mesothelioma, rhabdomyosarcoma
• Patients after failure of first-line chemotherapy (anthracyclines with/without ifosfamide) with or without RHT
• Progressive or recurrent tumor which is unresectable or only resectable with adverse functional outcome
• After macroscopic incomplete resection or marginal resection (tumor-free margins < 1 cm)
• Prior chemotherapy, including anthracyclines with/without ifosfamide (with or without RHT) or patients who cannot be given these medicines
• At least one tumor manifestation which is eligible for hyperthermia
• Performance status (ECOG) 0,1 or 2
• More than 3 weeks from last treatment
• Neutrophil count ≥ 1,5 G/l, hemoglobin ≥ 9 g/dl, platelets ≥ 100 G/l
• Albumin ≥ 25 g/l, total bilirubin ≤ 1 x ULN, ALT/AST ≤ 2.5 x ULN, AP ≤ 2.5 x ULN, Cockroft and Gault's calculated creatinine clearance ≥ 30 ml/min, CPK ≤ 2.5 x ULN
• Patients with the ability to follow study instructions and likely to attend and complete all required visits
• Written informed consent of the subject

Exclusion Criteria:

• Uncontrolled infection (e.g. active viral hepatitis)
• Unstable cardiac status
• Peripheral neuropathy > grade 2
• Known or persistent abuse of medications, drugs or alcohol
• Other malignancy during the last 5 years (exclusion of basal cell carcinoma or adequately treated cervical carcinoma in situ)
• Prior therapy with Tr or known history of hypersensitivity to drugs with a similar chemical structure
• Pregnancy or breast-feeding
• Females of childbearing potential, who are not using and not willing to use medically reliable methods of contraception for the entire study duration
• Uncontrolled CNS-metastases
• Medical or technical impossibility for hyperthermia to heat the major target lesion