Sarcoma
Conditions
Keywords
high-risk soft tissue sarcoma, trabectedin
Brief summary
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.
Interventions
DRUGTrabectedin
GENETICDNA double-strand breaks
The rationale for combining Tr and RHT is based on immune mechanisms induced by local heating of which are independent of the anti-tumor effects of Tr. Recent results demonstrate that an acute inflammation at the site of the heated tumor area and danger signals are responsible for immune reactions against tumor and metastases (Frey 2012). Abscopal effects after local radiation of tumors with response of distant metastases are induced by similar mechanisms like heat stress (Formenti 2013, Golden 2015). The long-term results for soft-tissue sarcoma are consistent with abscopal effects induced by RHT in a randomized trial compared to chemotherapy alone (Issels 2018).
Sponsors
Ludwig-Maximilians - University of Munich
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free Survival (PFS) | planned after 46 events after start of recruitment which are expected to occur after 27 month |
Secondary
| Measure | Time frame |
|---|---|
| Treatment related toxicity (hematological, renal, hepatic, others) | planned after 46 events after start of recruitment which are expected to occur after 27 month |
| Radiological response according to RECIST | planned after 46 events after start of recruitment which are expected to occur after 27 month |
| Overall Survival (OS) | planned after 46 events after start of recruitment which are expected to occur after 27 month |
Countries
Germany
Outcome results
None listed