Hyper-Thermia Enhanced Anti-tumor Efficacy of Trabectedin

NCT ID: NCT02359474

Last Updated: 2023-02-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-19
• Study Completion Date: 2023-08-31

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.

Conditions

Sarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Trabectedin with regional hyperthermia

Trabectedin 1.5 mg/m², 24 hrs continuous i.v. infusion, repetition after 21 days, until progress of disease.

Additional treatment with regional hyperthermia (RHT): RHT treatment of the tumor area and the surrounding tissue (41-44°C for 60 min treatment time) is applied at the end of Trabectedin infusion (+/- 4 hrs).

Group Type: EXPERIMENTAL

Trabectedin

Intervention Type: DRUG

DNA double-strand breaks

Intervention Type: GENETIC

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).

Trabectedin

Trabectedin 1.5 mg/m², 24 hrs continuous i.v. infusion, repetition after 21 days, until progress of disease.

Group Type: ACTIVE_COMPARATOR

Trabectedin

Intervention Type: DRUG

DNA double-strand breaks

Intervention Type: GENETIC

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).

Interventions

Trabectedin

Intervention Type: DRUG

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).

Intervention Type: GENETIC

Other Intervention Names

Yondelis

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role: lead

Responsible Party

Eric Kampmann

Dr. med.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rolf Issels, MD

Role: PRINCIPAL_INVESTIGATOR

Ludwig-Maximilians - University of Munich

Locations

Ludwig-Maximilians University of Munich, Klinikum Großhadern

Munich, Bavaria, Germany

Helios Klinikum Bad Saarow

Bad Saarow, , Germany

Charité - Universitätsmedizin Berlin

Berlin, , Germany

Helios Klinikum Berlin-Buch

Berlin, , Germany

Universitätsklinikum Erlangen

Erlangen, , Germany

Countries

Germany

Other Identifiers

HyperTET

Identifier Type: -

Identifier Source: org_study_id