HyperTET: Hyper-Thermia Enhanced Anti-tumor Efficacy of Trabectedin

Sponsor
Ludwig-Maximilians - University of Munich (Other)
Overall Status
Unknown status
CT.gov ID
NCT02359474
Collaborator
(none)
120
5
2
90
24
0.3

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Trabectedin Combined With Regional Hyperthermia as Second Line Treatment for Adult Patients With Advanced Soft-tissue Sarcoma
Study Start Date :
Jan 1, 2015
Anticipated Primary Completion Date :
Jul 1, 2022
Anticipated Study Completion Date :
Jul 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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).

Drug: Trabectedin
Other Names:
  • Yondelis
  • 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).

    Active Comparator: Trabectedin

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

    Drug: Trabectedin
    Other Names:
  • Yondelis
  • 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).

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free Survival (PFS) [planned after 46 events after start of recruitment which are expected to occur after 27 month]

    Secondary Outcome Measures

    1. Radiological response according to RECIST [planned after 46 events after start of recruitment which are expected to occur after 27 month]

    2. Overall Survival (OS) [planned after 46 events after start of recruitment which are expected to occur after 27 month]

    3. Treatment related toxicity (hematological, renal, hepatic, others) [planned after 46 events after start of recruitment which are expected to occur after 27 month]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ludwig-Maximilians University of Munich, Klinikum Großhadern Munich Bavaria Germany 81377
    2 Helios Klinikum Bad Saarow Bad Saarow Germany
    3 Charité - Universitätsmedizin Berlin Berlin Germany
    4 Helios Klinikum Berlin-Buch Berlin Germany
    5 Universitätsklinikum Erlangen Erlangen Germany

    Sponsors and Collaborators

    • Ludwig-Maximilians - University of Munich

    Investigators

    • Principal Investigator: Rolf Issels, MD, Ludwig-Maximilians - University of Munich

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Eric Kampmann, Dr. med., Ludwig-Maximilians - University of Munich
    ClinicalTrials.gov Identifier:
    NCT02359474
    Other Study ID Numbers:
    • HyperTET
    First Posted:
    Feb 10, 2015
    Last Update Posted:
    Jul 15, 2019
    Last Verified:
    Jul 1, 2019
    Keywords provided by Eric Kampmann, Dr. med., Ludwig-Maximilians - University of Munich
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 15, 2019