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Hyper-Thermia Enhanced Anti-tumor Efficacy of Trabectedin (HyperTET)

Primary Purpose

Sarcoma

Status

Active

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

Trabectedin

DNA double-strand breaks

About this trial

This is an interventional treatment trial for Sarcoma focused on measuring high-risk soft tissue sarcoma, trabectedin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Ludwig-Maximilians University of Munich, Klinikum Großhadern
Helios Klinikum Bad Saarow
Charité - Universitätsmedizin Berlin
Helios Klinikum Berlin-Buch
Universitätsklinikum Erlangen

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Trabectedin with regional hyperthermia

Trabectedin

Arm Description

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).

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

Outcomes

Primary Outcome Measures

Progression-free Survival (PFS)

Secondary Outcome Measures

Radiological response according to RECIST

Overall Survival (OS)

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

Full Information

NCT ID

NCT02359474

First Posted

November 10, 2014

Last Updated

February 27, 2023

Sponsor

Ludwig-Maximilians - University of Munich

1. Study Identification

Unique Protocol Identification Number

NCT02359474

Brief Title

Hyper-Thermia Enhanced Anti-tumor Efficacy of Trabectedin

Acronym

HyperTET

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

December 19, 2014 (Actual)

Primary Completion Date

August 2023 (Anticipated)

Study Completion Date

August 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Ludwig-Maximilians - University of Munich

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sarcoma

Keywords

high-risk soft tissue sarcoma, trabectedin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

120 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Trabectedin with regional hyperthermia

Arm Type

Experimental

Arm Description

Arm Title

Trabectedin

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Trabectedin

Other Intervention Name(s)

Yondelis

Intervention Type

Genetic

Intervention Name(s)

DNA double-strand breaks

Intervention Description

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).

Primary Outcome Measure Information:

Title

Progression-free Survival (PFS)

Time Frame

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

Secondary Outcome Measure Information:

Title

Radiological response according to RECIST

Time Frame

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

Title

Overall Survival (OS)

Time Frame

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

Title

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

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rolf Issels, MD

Organizational Affiliation

Ludwig-Maximilians - University of Munich

Official's Role

Principal Investigator

Facility Information:

Facility Name

Ludwig-Maximilians University of Munich, Klinikum Großhadern

City

Munich

State/Province

Bavaria

ZIP/Postal Code

81377

Country

Germany

Facility Name

Helios Klinikum Bad Saarow

City

Bad Saarow

Country

Germany

Facility Name

Charité - Universitätsmedizin Berlin

City

Berlin

Country

Germany

Facility Name

Helios Klinikum Berlin-Buch

City

Berlin

Country

Germany

Facility Name

Universitätsklinikum Erlangen

City

Erlangen

Country

Germany

12. IPD Sharing Statement

Learn more about this trial

Hyper-Thermia Enhanced Anti-tumor Efficacy of Trabectedin

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