Hyper-Thermia Enhanced Anti-tumor Efficacy of Trabectedin

Sarcoma Clinical Trial

— HyperTET  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02359474
• Other study ID #: HyperTET
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 19, 2014
• Est. completion date: August 2023

Study information

• Verified date: February 2023
• Source: Ludwig-Maximilians - University of Munich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: August 2023
• Est. primary completion date: August 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Sarcoma

Intervention

Drug:
• Trabectedin

Genetic:
• DNA 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).

Locations

Country	Name	City	State
Germany	Helios Klinikum Bad Saarow	Bad Saarow
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Helios Klinikum Berlin-Buch	Berlin
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	Ludwig-Maximilians University of Munich, Klinikum Großhadern	Munich	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
Ludwig-Maximilians - University of Munich

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)		planned after 46 events after start of recruitment which are expected to occur after 27 month
Secondary	Radiological response according to RECIST		planned after 46 events after start of recruitment which are expected to occur after 27 month
Secondary	Overall Survival (OS)		planned after 46 events after start of recruitment which are expected to occur after 27 month
Secondary	Treatment related toxicity (hematological, renal, hepatic, others)		planned after 46 events after start of recruitment which are expected to occur after 27 month