Hyper-Thermia Enhanced Anti-tumor Efficacy of Trabectedin

NCT02359474 | Unknown Phase 2

• 1 other identifier: HyperTET
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 5

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

Keywords

high-risk soft tissue sarcoma; trabectedin

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  planned after 46 events after start of recruitment which are expected to occur after 27 month

Secondary Outcomes (3)

• 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

• Treatment related toxicity (hematological, renal, hepatic, others)

  planned after 46 events after start of recruitment which are expected to occur after 27 month

Study Arms (2)

Trabectedin with regional hyperthermia

EXPERIMENTAL

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).

Drug: Trabectedin; Genetic: DNA double-strand breaks

Trabectedin

ACTIVE COMPARATOR

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

Drug: Trabectedin; Genetic: DNA double-strand breaks

Interventions

Trabectedin DRUG

Also known as: Yondelis

Trabectedin; Trabectedin with regional hyperthermia

DNA double-strand breaks 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 with regional hyperthermia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Uncontrolled infection (e.g. active viral hepatitis)
• Unstable cardiac status
• Peripheral neuropathy \> grade 2
• Known or persistent abuse of medications, drugs or alcohol
• 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

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead

Study Sites (5)

Ludwig-Maximilians University of Munich, Klinikum Großhadern

Munich, Bavaria, 81377, Germany

Location

Helios Klinikum Bad Saarow

Bad Saarow, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, Germany

Location

Helios Klinikum Berlin-Buch

Berlin, Germany

Location

Universitätsklinikum Erlangen

Erlangen, Germany

Location

MeSH Terms

Conditions

Sarcoma

Interventions

Trabectedin; DNA Breaks, Double-Stranded

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; DNA Breaks; DNA Damage; Genetic Phenomena

Study Officials

• Rolf Issels, MD

  Ludwig-Maximilians - University of Munich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. med.

Study Record Dates

• First Submitted: November 10, 2014
• First Posted: February 10, 2015
• Study Start: December 19, 2014
• Primary Completion: August 1, 2023
• Study Completion: August 1, 2023
• Last Updated: February 28, 2023

Record last verified: 2023-02

Locations

DE (5)