tTF-NGR Randomized Study - STS

NCT05597917 | Recruiting Phase 3 DMC

• 3 other identifiers: WWU19_00072024-516392-33-002020-005858-21
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 9

Brief Summary

In this phase III open label, controlled clinical trial patients with unresectable or metastatic soft-tissue sarcoma after failure of anthracycline-containing first line therapy or with contraindications to these drugs and CD13 positivity in central histology (grade \>/= 1+) are treated to evaluate whether tTF-NGR in combination with standard trabectedin chemotherapy prolongs progression-free survival (according to iRECIST), as compared with trabectedin alone. Further objectives are to evaluate the efficacy of tTF-NGR in combination with standard trabectedin chemotherapy with respect to the response rate and overall survival as well as to assess the safety profile of tTF-NGR combined with trabectedin. Before the randomized phase III part of the study, there was a safety run-in part. The final dose of tTF-NGR established as safe in this safety run-in part is 0.5 mg/m2 per day for 2 consecutive days following each trabectedin infusion and is used for the randomized (parallel 1:1; Arm 1: standard trabectedin, Arm 2: standard trabectedin plus tTF-NGR) phase III part of this trail. . Further dose modification for tTF-NGR is possible.

Conditions

Soft Tissue Sarcoma

Keywords

tTF-NGR; vascular targeting; CD13; aminopeptidase N; Trabectedin

Outcome Measures

Primary Outcomes (1)

• Efficacy: Prolongation of progression-free survival (PFS) according to iRECIST as judged by central radiology in a blinded fashion after end of trial.

  The primary objective of the trial is to evaluate whether tTF-NGR in combination with standard trabectedin chemotherapy given for unresectable or metastatic soft tissue sarcoma after failure of anthracycline-containing first line therapy or with contraindications to these drugs prolongs progression-free survival, as compared with trabectedin alone. The following efficacy endpoint (for the randomized phase III part) will be considered: \- Progression-free survival (PFS) according to iRECIST (Seymour L, Lancet Oncol. 2017) as judged by central radiology in a blinded fashion after end of trial.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcomes (18)

• Evaluation of the efficacy of tTF-NGR in combination with standard trabectedin chemotherapy (OOR)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Evaluation of the efficacy of tTF-NGR in combination with standard trabectedin chemotherapy (DCR)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Evaluation of the efficacy of tTF-NGR in combination with standard trabectedin chemotherapy (mPFS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Evaluation of the efficacy of tTF-NGR in combination with standard trabectedin chemotherapy (mOS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Evaluation of the efficacy of tTF-NGR in combination with standard trabectedin chemotherapy (OS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Study Arms (2)

Arm 1: Standard chemotherapy with trabectidin (in-label)

ACTIVE COMPARATOR

Patients will receive standard trabectedin 1.5 mg/m2 as a 24-hour central intravenous (IV) infusion on day 1, q d 22 x until disease progression or contraindications against further application.

Drug: Trabectedin

Arm 2: tTF-NGR added to standard trabectedin

EXPERIMENTAL

Patients will receive standard trabectedin according to arm 1 plus 0.5 mg/m2 tTF-NGR (1-hour ratecontrolled infusion, port central venous access, 0.9 % NaCl ad 100 mL) on days 2 and 3 following each trabectedin cycle (within 1 hour interval between end of trabectedin infusion and tTF-NGR: e.g.: trabectedin on monday 8 am to tuesday 8 am followed by tTF-NGR on tuesday 9 am and on the following day, q d 22 x until disease progression or contraindications against further application.

Drug: Trabectedin; Biological: tTF-NGR

Interventions

Trabectedin DRUG

Patients will receive standard trabectedin 1.5 mg/m2 as a 24-hour central intravenous (IV) infusion on day 1, q d 22 x until disease progression or contraindications against further application.

Also known as: Yondelis

Arm 1: Standard chemotherapy with trabectidin (in-label); Arm 2: tTF-NGR added to standard trabectedin

tTF-NGR BIOLOGICAL

Patients will receive standard trabectedin according to arm 1 plus 0.5 mg/m2 of tTF-NGR (1-hour ratecontrolled infusion, port central venous access, 0.9 % NaCl ad 100 mL) on days 2 and 3 following each trabectedin cycle (within 1 hour interval between end of trabectedin infusion and tTF-NGR: e.g.: trabectedin on monday 8 am to tuesday 8 am followed by tTF-NGR on tuesday 9 am and on the following day, q d 22 x until disease progression or contraindications against further application.

Arm 2: tTF-NGR added to standard trabectedin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients of all genders (female, male, diverse), with no restriction regarding ethnic or religious background age 18 - 75 years.
• Patients with advanced or metastatic soft-tissue sarcoma after failure of anthracycline-containing first line therapy (or anthracycline-containing adjuvant therapy within 12 months before entry on study) or with contraindications to these drugs
• Patients must have histological evidence of high-grade advanced unresectable or metastatic soft tissue sarcoma (grade 2 - 3) according to the FNCLCC grading system. The following tumor types are included:
• Dedifferentiated liposarcoma
• Myxoid liposarcoma (high grade)
• Pleomorphic liposarcoma
• Adult fibrosarcoma
• Myxofibrosarcoma (high-grade)
• Leiomyosarcoma
• Rhabdomyosarcoma (alveolar, pleomorphic)
• Angiosarcoma
• Synovial sarcoma
• Undifferentiated sarcoma
• Tumor types not listed above may be included upon communication with Coordinating Investigator.
• The following tumor types will not be included:

You may not qualify if:

• curative therapy available
• clinically significant unrelated illness, which in the judgement of the investigators could compromise the patient's ability to tolerate the IMP or be likely to interfere with the study procedures or results
• immobilized tumor patients (wheel chair etc.) with increased risk for DVT
• known hypersensitivity reactions to prior application of E. coli-derived material
• known hereditary syndromes with elevated thromboembolic risk (FV Leiden and prothrombin mutations (G20210A), hereditary antithrombin, protein C and S deficiency, and antiphospholipid syndrome) after one or more clinical thromboembolic events
• patients with hereditary vascular disorders (such as Klippel-Trenauny-Weber syndrome) with increased thromboembolic risk.
• patients with a Khorana score of (Khorana AA, et al. J.Clin. Oncol. 2009, 27, 4839-4847, attached to this protocol) of \> 3
• elevated Troponin T hs (\> 50 ng/L) or elevated Troponin I hs before entry on study
• presence of active central nervous system (CNS) disease and/or CNS vascular abnormalities detected by MRI or CT
• no adequate bone marrow function, absolute neutrophil count (ANC) \< 1.0 x 109/L, platelets \< 50 x 109/L (for trabectedin actually \< 100 x 109/L - to be decided by the investigator on an individual patient basis) and haemoglobin (Hb) \< 8.0 g/dl.
• chronically impaired renal function or creatinine ≥ 2.0 x upper limit of normal (ULN).
• inadequate liver function (alanine aminotranserase (ALT), aspartate aminotranserase (AST), alkaline phosphatase (ALP) or total bilirubin ≥ 2.5 x ULN) unless due to liver metastasis (decision by the investigator)
• fibrinogen \< 150 mg/dL, and/or International Normalized Ratio (INR) \> 1,5 (global coagulation parameters can be discussed with the Coordinating Investigator prior to entry on study)
• females of childbearing potential as well as fertile males who do not agree to use a highly effective form of contraception (Pearl Index \< 1) during the study and for 3 months (females) following the last trabectedin (Arm 1) or last study drug (Arm 2) administration and 5 months (males) following the last dose of trabectedin (Arm 1) or study drug (Arm 2)
• women with breast-feeding activity

Sponsors & Collaborators

• Universität Münster: lead
• Anturec Pharmaceuticals GmbH: collaborator

Study Sites (9)

HELIOS Klinikum Bad Saarow

Bad Saarow, 15529, Germany

RECRUITING

HELIOS Klinikum Berlin-Buch

Berlin, 13125, Germany

RECRUITING

TU Dresden Medizinische Fakultät Carl Gustav Carus

Dresden, 01307, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, 30625, Germany

RECRUITING

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

RECRUITING

Universitätsmedizin Mainz

Mainz, 55131, Germany

RECRUITING

Klinikum rechts der Isar der technischen Universität München

München, 81675, Germany

RECRUITING

LMU Klinikum

Münich, 81377, Germany

RECRUITING

University Hospital Muenster, Germany

Münster, 48149, Germany

RECRUITING

MeSH Terms

Conditions

Sarcoma

Interventions

Trabectedin

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

Study Officials

• Christoph Schliemann, Prof. Dr.

  University Hospital Muenster (Department of Medicine A), Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christoph Schliemann, Prof. Dr.

CONTACT

+49 251 83 45363; Christoph.Schliemann@ukmuenster.de

Torsten Kessler, PD Dr.

CONTACT

+49 251 83 45363; Torsten.Kessler@ukmuenster.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2021
• First Posted: October 28, 2022
• Study Start: October 26, 2021
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: within 6 months of study completion

Locations

DE (9)