Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2024-516392-33-00 | EU Trial (CTIS) Number | ||
| 2020-005858-21 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Anturec Pharmaceuticals GmbH | UNKNOWN |
Not provided
Not provided
Not provided
Not provided
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.
Rationale: tTF-NGR targets CD13 present in tumor-associated vasculature and on tumor cells of the majority of STS tissue samples examined; preclinical data on combination of tTF-NGR with anthracyclines and trabectedin; low competition of targeted or immune therapy in soft tissue sarcoma (STS)
Investigational Medicinal Product: Patients will receive a dose of the Investigational Medicinal Product (IMP) tTF-NGR determined to be safe within the safety run-in cohort of the study as 1-hour rate-controlled infusion (port central venous access, 0.9 % NaCl ad 100 mL) per day for 2 consecutive days 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 latest 9 am and on the following day, q d 22 x until disease progression or contraindications against further application.
Indication: Unresectable or metastatic STS after failure of anthracycline-containing first line treatment or with contraindications to these drugs; CD13 positivity in central histology (grade >/= 1+)
Primary objective and endpoints: 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.
Secondary objectives and endpoints: The secondary objective of the trial is to evaluate the efficacy of tTF-NGR in combination with standard trabectedin chemotherapy given for unresectable or metastatic STS after failure of anthracycline-containing first line therapy or with contraindications to these drugs with respect to the response rate and overall survival as well as to assess the safety profile of tTF-NGR combined with trabectedin.
To assess the efficacy, the following measurements will be considered:
To assess the safety profile of tTF-NGR combined with trabectedin (for the phase II and the phase III parts), the following safety endpoints will be considered:
Study design: Open label, randomized, controlled study in subjects with metastatic or refractory soft tissue sarcoma. Approx. 150 patients will be screened, 126 evaluable patients are enrolled and parallel assigned in a 1:1 fashion to one of two different arms, as outlined below. Randomization will be stratified into CD13+ grades 1 and 2 versus CD13+ grade 3 and number of chemotherapy regimen before entry on trial: 1 versus >1.
Safety run-in part:
Before the randomized phase III part of the study, there was a safety cohort of a minimum of 6 patients obtaining at least 2 cycles each of the combination outlined in arm 2 (see below) to confirm safety of this combination (1.5 mg/m2 trabectedin plus a starting dose of 3 mg/m2 tTF-NGR). The patients were treated in-house and in sequence. In case of dose-limiting toxicity (DLT) in one patient of this cohort, a dosemodification protocol for tTF-NGR to 2 mg/m2 was planned, and in case of further tolerability problems in one patient further deescalations in 0.5 mg/m2 steps of tTF-NGR and/or by a reduction of application days were planned. The safety part of the study is completed and the safe dose of tTF-NGR for the randomized phase III part of the study is 0.5 mg/m2 given on days 2 and 3. Since 6 patients tolerated >/= 2 cycles of this dose without DLT, DLT should occur in \
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of the efficacy of tTF-NGR in combination with standard trabectedin chemotherapy (OOR) | To assess the efficacy, the following measurement will be considered: Overall response rate (ORR, consisting of CR and PR) | 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 |
Not provided
Inclusion Criteria:
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:
Tumor types not listed above may be included upon communication with Coordinating Investigator.
The following tumor types will not be included:
CD13 positivity with a score of ≥ 1 (20) by central pathology (GDI Münster)
Patients must have at least one unidimensionally measurable lesion by computed tomography as defined by RECIST criteria 1.1. Other adequate imaging procedures such as MRI are allowed. This lesion should not have been irradiated during previous treatments
Life expectancy of at least 3 months
Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
No contraindications for trabectedin (see attachment)
Negative serum pregnancy test for females of childbearing potential* within 14 days of starting treatment
Informed consent signed and dated to participate in the study
Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures
Exclusion Criteria:
NOTE: Outliers of laboratory values can be disregarded and set aside as exclusion criteria by a Coordinating Investigator´s decision. The conditions for the use of trabectedin as specified in the Summary of Product Characteristics are to be followed according to institutional guidelines for standard of care.
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| 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 |
| Name | Affiliation | Role |
|---|---|---|
| Christoph Schliemann, Prof. Dr. | University Hospital Muenster (Department of Medicine A), Germany | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| HELIOS Klinikum Bad Saarow | Recruiting | Bad Saarow | 15529 | Germany |
De-identified participant data for all primary and secondary outcome measurements will be made available within 6 months of study completion
within 6 months of study completion
Not provided
Not provided
| ID | Term |
|---|---|
| D012509 | Sarcoma |
| ID | Term |
|---|---|
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077606 | Trabectedin |
| ID | Term |
|---|---|
| D004149 | Dioxoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D044005 | Tetrahydroisoquinolines |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| 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. |
|
| Evaluation of the efficacy of tTF-NGR in combination with standard trabectedin chemotherapy (DCR) | To assess the efficacy, the following measurement will be considered: - Disease control rate (DCR, consisting of CR, PR, and stable disease (SD) for >18 weeks) | 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) | To assess the efficacy, the following measurement will be considered: - Median progression-free survival (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) | To assess the efficacy, the following measurement will be considered: - Median overall survival (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) | To assess the efficacy, the following measurement will be considered: - Overall survival (OS) rate at 12 and 18 months | 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 safety profile of tTF-NGR combined with standard trabectedin chemotherapy (AE) | To assess the safety profile of tTF-NGR combined with trabectedin the following safety endpoint will be considered: - Adverse Events (AEs) assessment based on CTCAE v.5.0. | 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 safety profile of tTF-NGR combined with standard trabectedin chemotherapy (Standard laboratory parameters) | To assess the safety profile of tTF-NGR combined with trabectedin the following safety endpoint will be considered: - laboratory parameter: Troponin T hs [ng/l] | 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 safety profile of tTF-NGR combined with standard trabectedin chemotherapy (Physical examination: Height) | To assess the safety profile of tTF-NGR combined with trabectedin the following safety endpoint will be considered: - Physical examination: Height [m] | 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 safety profile of tTF-NGR combined with standard trabectedin chemotherapy (Physical examination: Weight) | To assess the safety profile of tTF-NGR combined with trabectedin the following safety endpoint will be considered: - Physical examination: Weight [kg] | 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 safety profile of tTF-NGR combined with standard trabectedin chemotherapy (Physical examination: Body surface) | To assess the safety profile of tTF-NGR combined with trabectedin the following safety endpoint will be considered: - Physical examination: Body surface area [m2] | 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 safety profile of tTF-NGR combined with standard trabectedin chemotherapy (Vital sign: breathing) | To assess the safety profile of tTF-NGR combined with trabectedin the following safety endpoint will be considered: - Physical examination: Vital sign: breathing rate by watching and counting [breaths per minute] | 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 safety profile of tTF-NGR combined with standard trabectedin chemotherapy (Vital sign: consciousness) | To assess the safety profile of tTF-NGR combined with trabectedin the following safety endpoint will be considered: - Physical examination: Vital sign: consciousness by talking to the patient | 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 safety profile of tTF-NGR combined with standard trabectedin chemotherapy (Vital sign: heart rate) | To assess the safety profile of tTF-NGR combined with trabectedin the following safety endpoint will be considered: - Physical examination: Vital sign: heart rate by pulse [beats per minute] | 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 safety profile of tTF-NGR combined with standard trabectedin chemotherapy (Physical examination: ECOG perfomance status) | To assess the safety profile of tTF-NGR combined with trabectedin the following safety endpoint will be considered: - Physical examination: ECOG perfomance status | 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 safety profile of tTF-NGR combined with standard trabectedin chemotherapy (ECG) | To assess the safety profile of tTF-NGR combined with trabectedin the following safety endpoint will be considered: - ECG (rythm, puls rate, Vector, P Wave, PQ time, QRS Complex, R progression from V1 to V6, QT Interval, PQ time, QRS time, T wave) | 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 safety profile of tTF-NGR combined with standard trabectedin chemotherapy (Echocardiography) | To assess the safety profile of tTF-NGR combined with trabectedin the following safety endpoint will be considered: - Echocardiography (diameters of both atria and left and right cardiac chambers at end-diastolic and end-systolic times [mm], ejection fraction [%], wall diameters [mm]) | 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 safety profile of tTF-NGR combined with standard trabectedin chemotherapy (PRO) | To assess the safety profile of tTF-NGR combined with trabectedin the following safety endpoint will be considered: - Patient reported outcomes (PRO) by EORTC QLQ C30 questionnaire | 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 safety profile of tTF-NGR combined with standard trabectedin chemotherapy (PK) | To assess the safety profile of tTF-NGR combined with trabectedin the following safety endpoint will be considered: - pharmacokinetics: AUC [ng*h/ml] | 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 |
| HELIOS Klinikum Berlin-Buch | Recruiting | Berlin | 13125 | Germany |
|
| TU Dresden Medizinische Fakultät Carl Gustav Carus | Recruiting | Dresden | 01307 | Germany |
|
| Medizinische Hochschule Hannover | Recruiting | Hanover | 30625 | Germany |
|
| Universitätsklinikum Heidelberg | Recruiting | Heidelberg | 69120 | Germany |
|
| Universitätsmedizin Mainz | Recruiting | Mainz | 55131 | Germany |
|
| Klinikum rechts der Isar der technischen Universität München | Recruiting | München | 81675 | Germany |
|
| LMU Klinikum | Recruiting | Münich | 81377 | Germany |
|
| University Hospital Muenster, Germany | Recruiting | Münster | 48149 | Germany |
|
| D007546 |
| Isoquinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |