Unresectable or metastatic soft tissue sarcoma MedDRA version: 15.1 Level: HLGT Classification code 10041299 Term: Soft tissue sarcomas System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10075333 Term: Soft tissue sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Onfekafusp alfa
Product Code: L19TNF
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Onfekafusp alfa
CAS Number: 1957239-88-1
Other descriptive name: L19TNF
Concentratio
Sponsors
Philogen S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients must have histological evidence of advanced unresectable and/or metastatic high-grade soft tissue sarcoma (grade 2 – 3 according to the FNLCC grading system) not amenable to curative treatment with surgery or radiotherapy. The following tumor types are included: – Malignant fibrous histiocytoma – Myxoid and round cell liposarcoma, pleomorphic liposarcoma or dedifferentiated – Liposarcoma – Pleomorphic rhabdomyosarcoma – Myxofibrosarcoma intermediate and high-grade – Fibrosarcoma – Leiomyosarcoma – Angiosarcoma – Alveolar rhabdomyosarcoma – Unclassified sarcoma NOS The following tumor types will not be included: – GIST – Mixed mesodermal tumor – Chondrosarcoma – Synovial sarcoma – Malignant peripheral nerve sheath tumor – Epithelioid sarcoma – Embryonal rhabdomyosarcoma – Malignant mesothelioma – Neuroblastoma – Osteosarcoma – Ewing's sarcoma / primitive neuroectodermal tumor – Desmoplastic small round cell tumor – Alveolar soft part sarcoma • Patients aged 18-75 years. • No prior therapy (except surgery and radiation) for the advanced or metastatic stage of soft tissue sarcoma. • Patients who had received prior anthracyclines will not be eligible. • Patients must have at least one unidimensionally measurable lesion by computed tomography as defined by RECIST criteria 1.1. This lesion should not have been irradiated during previous treatments. • Eastern Cooperative Oncology Group (ECOG) performance status of = 2. • Life expectancy of at least 3 months. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 28
Exclusion criteria
Exclusion criteria: 1. Prior therapy (except surgery and radiation) for unresectable or metastatic malignant soft tissue sarcoma. 2. Previous treatment with anthracycline-containing chemotherapy. 3. Radiotherapy within 4 weeks prior therapy. 4. Known history of allergy to TNFa, anthracyclines or other intravenously administered human proteins/peptides/antibodies. 5. Absolute neutrophil count (ANC) Grade II, New York Heart Association (NYHA) criteria). 11. Clinically significant cardiac arrhythmias or requiring permanent medication. 12. Uncontrolled hypertension, despite optimal therapy. 13. Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine classification). 14. Severe diabetic retinopathy such as severe non-proliferative retinopathy and proliferative retinopathy. 15. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery) within 4 weeks of administration of study treatment. 16. Pregnancy or breast-feeding. 17. Requirement of chronic administration of corticosteroids or other immunosuppressant drugs. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterion. 18. Presence of active and uncontrolled infections or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study. 19. Known active or latent tuberculosis (TB). 20. Concurrent malignancies other than Soft Tissue Sarcoma, unless the patient has been disease-free for at least 2 years. 21. Growth factors or immunomodulatory agents within 7 days prior to the administration of study treatment. 22. Serious, non-healing wound, ulcer or bone fracture. 23. Allergy to study medication or excipients in study medication. 24. Concurrent therapy with oral anticoagulants . 25. Concurrent use of other anti-cancer treatments or agents other than study medication
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the trial is to evaluate whether L19TNF in combination with doxorubicin given for advanced or metastatic soft tissue sarcoma prolongs progression free survival, as compared to doxorubicin alone. The following efficacy endpoint will be considered: - Progression-free survival (PFS);Secondary Objective: To assess the efficacy, the following measurements will be considered: - Overall survival (OS) - Median Progression Free Survival (mPFS) - Median Overall Survival (mOS). - Overall Response Rate (ORR, consisting of CR and PR) and Best Overall Response Rate (BORR) To assess the safety profile of L19TNF combined with doxorubicin. The following safety endpoints will be considered: - Adverse Events (AEs) assessment based on CTCAE v.4.03. - Standard laboratory (haematology, biochemistry and urinalysis) parameters. - Physical examination findings including assessment of vital signs and physical measurements.;Primary end point(s): The primary objective of the trial is to evaluate whether L19TNF in combination with doxorubicin given for advanced or metastatic soft tissue sarcoma prolongs progression free survival, as compared to doxorubicin alone. The following efficacy endpoint will be considered: - Progression-free survival (PFS);Timepoint(s) of evaluation of this end point: End of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To assess the efficacy, the following measurements will be considered: - Overall survival (OS) - Median Progression Free Survival (mPFS) - Median Overall Survival (mOS). - Overall Response Rate (ORR, consisting of CR and PR) and Best Overall Response Rate (BORR) To assess the safety profile of L19TNF combined with doxorubicin. The following safety endpoints will be considered: - Adverse Events (AEs) assessment based on CTCAE v.4.03. - Standard laboratory (haematology, biochemistry and urinalysis) parameters. - Physical examination findings including assessment of vital signs and physical measurements.;Timepoint(s) of evaluation of this end point: - Median Overall survival (mOS). - Overall response rate (ORR, consisting of CR and PR). - Progression-free survival (PFS) rate at 3, 6, 9, 12 and 18 months. - Overall survival (OS) rate at 12 and 18 months. Safety profile of L19TNF combined with doxorubicin: throughout the study | — |
Countries
Germany, Spain
Contacts
Public ContactHead of Clinical Operations
Sofpromed Investigación Clínica, SLU
Outcome results
None listed