Clinical trial • Phase III • Oncology|Rare Disease
ONFEKAFUSP ALFA for Soft tissue sarcoma|Advanced soft tissue sarcoma|Metastatic soft tissue sarcoma
Phase III trial of ONFEKAFUSP ALFA for Soft tissue sarcoma|Advanced soft tissue sarcoma|Metastatic soft tissue sarcoma.
Overview
- Trial Therapeutic Area
- Oncology|Rare Disease
- Trial Disease
- Soft tissue sarcoma|Advanced soft tissue sarcoma|Metastatic soft tissue sarcoma
- Trial Stage
- Phase III
- Drug Modality
- Other antibody|Small molecule
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 29-03-2024
- First CTIS Authorization Date
- 03-05-2024
Trial design
Randomised, open-label, arm 1: doxorubicin alone (doxorubicin administered on day 1 every 3 weeks; doxorubicin product detailed as 2 mg/ml solution for injection; dosing units mg/m2, max daily dose 75 mg/m2, max total dose 450 mg/m2). arm 2: doxorubicin (day 1 every 3 weeks) plus l19tnf (fibromun) given on days 1, 3 and 5 every 3 weeks; maintenance (investigator discretion) consisting of l19tnf on day 1 of every 21-day maintenance cycle until 18 months after study treatment start.-controlled Phase III trial in Germany, Spain, France and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Arm 1: Doxorubicin alone (Doxorubicin administered on Day 1 every 3 weeks; Doxorubicin product detailed as 2 mg/ml Solution for Injection; dosing units mg/m2, max daily dose 75 mg/m2, max total dose 450 mg/m2). Arm 2: Doxorubicin (Day 1 every 3 weeks) plus L19TNF (Fibromun) given on Days 1, 3 and 5 every 3 weeks; maintenance (investigator discretion) consisting of L19TNF on Day 1 of every 21-day maintenance cycle until 18 months after study treatment start.
- Target Sample Size
- 118
- Trial Duration For Participant
- 540
Eligibility
Recruits 118 No vulnerable populations selected. Participants are adults (18-75 years) and must provide signed and dated informed consent. Adult information and consent forms are provided; there are no assent procedures for minors (minors are excluded by age criteria)..
- Pregnancy Exclusion
- 17. Pregnancy or breast-feeding.
- Vulnerable Population
- No vulnerable populations selected. Participants are adults (18-75 years) and must provide signed and dated informed consent. Adult information and consent forms are provided; there are no assent procedures for minors (minors are excluded by age criteria).
Inclusion criteria
- {"criterion_text":"- 1. Age 18 - 75 years.\n- 2. Patients must have histological evidence of advanced unresectable and/or metastatic high-grade soft tissue sarcoma (grade 2 – 3 according to the FNCLCC grading system) not amenable to curative treatment with surgery or radiotherapy and for which doxorubicin treatment is considered appropriate. Participants with Osteosarcoma, Chondrosarcoma, Ewing Sarcoma/ Primitive Neuroectodermal Tumor (PNET), Kaposi’s Sarcoma, Dermatofibrosarcoma protuberans, and Gastrointestinal Stromal Tumors (GIST) will be excluded\n- 3. 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.\n- 4. Life expectancy of at least 3 months.\n- 5. ECOG ≤ 2.\n- 6. Documented negative test for HIV-HBV-HCV. For HBV serology: the determination of HBsAg and anti-HBcAg-Ab is required. In patients with serology documenting previous exposure to HBV, negative serum HBV-DNA is required. For HCV: HCV-RNA or HCV antibody test. Subjects with a positive test for HCV antibody but no detection of HCV-RNA indicating no current infection are eligible.\n- 7. Female patients: negative serum pregnancy test at screening for women of childbearing potential (WOCBP)*. WOCBP must agree to use, from the screening to six months following the last administration of L19TNF and/or Doxorubicin, highly effective contraception methods, as defined by the \"Recommendations for contraception and pregnancy testing in clinical trials\" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group (www.hma.eu/ctfg.html) and which include, for instance, progesterone-only or combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion, vasectomized partner or sexual abstinence. Male patients: Male subjects able to father children must agree to use two acceptable methods of contraception from the screening to four months following the last administration of L19TNF and/or Doxorubicin (e.g. condom with spermicidal gel). Double-barrier contraception is required.\n- 8. Informed consent signed and dated to participate in the study\n- 9. Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures. * Women of childbearing potential are defined as females who have experienced menarche, are not postmenopausal (12 months with no menses without an alternative medical cause) and are not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy)"}
Exclusion criteria
- {"criterion_text":"- 1. Prior therapy (except surgery and radiation) for unresectable or metastatic malignant soft tissue sarcoma.\n- 10. History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.\n- 11. Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).\n- 12. Clinically significant cardiac arrhythmias or requiring permanent medication.\n- 13. Uncontrolled hypertension, despite optimal therapy.\n- 14. Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine classification).\n- 15. Severe diabetic retinopathy such as severe non-proliferative retinopathy and proliferative retinopathy.\n- 16. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery) within 4 weeks of administration of study treatment.\n- 17. Pregnancy or breast-feeding.\n- 18. 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.\n- 19. 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.\n- 2. Previous treatment with anthracycline-containing chemotherapy.\n- 20. Known active or latent tuberculosis (TB).\n- 21. Concurrent malignancies other than Soft Tissue Sarcoma, unless the patient has been disease-free for at least 2 years.\n- 22. Growth factors or immunomodulatory agents within 7 days prior to the administration of study treatment.\n- 23. Serious, non-healing wound, ulcer or bone fracture.\n- 24. Allergy to study medication or excipients in study medication.\n- 25. Deep vein thrombosis, pulmonary embolism or other acute vascular events within 6 months.\n- 26. Anticoagulation therapy with P2Y12 antagonists (e.g., clopidogrel, ticagrelor) and vitamin K antagonists (e.g., phenprocoumon, warfarin)\n- 27. Concurrent use of other anti-cancer treatments or agents other than study medication.\n- 3. Radiotherapy within 4 weeks prior to therapy\n- 4. Known history of allergy to TNFα, anthracyclines or other intravenously administered human proteins/peptides/antibodies.\n- 5. Previous therapy with recombinant TNF.\n- 6. Absolute neutrophil count (ANC) < 1.5 x 109/L, platelets < 100 x 109/L and haemoglobin (Hb) < 9.0 g/dl.\n- 7. Chronically impaired renal function as expressed by creatinine ≥ 2.0 x ULN.\n- 8. Inadequate liver function (ALT, AST, ALP or total bilirubin ≥ 2.5 x ULN).\n- 9. Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol."}
Endpoints
Primary endpoints
- {"endpoint_text":"- The following efficacy endpoint will be considered: − Progression-free survival (PFS)","definition_or_measurement_approach":"Progression-free survival (PFS) assessed using radiologic tumour assessments per RECIST 1.1 (CT imaging as required by inclusion criterion 3)."}
Secondary endpoints
- {"endpoint_text":"- 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)","definition_or_measurement_approach":"Efficacy measured by survival endpoints (OS, mOS) and time-to-event analysis for PFS; tumour response endpoints (ORR, BORR) assessed by RECIST 1.1 via CT imaging."}
- {"endpoint_text":"- 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.","definition_or_measurement_approach":"Safety assessed by AE reporting graded per CTCAE v4.03, routine laboratory testing (haematology, biochemistry, urinalysis), and physical examinations/vital signs."}
Recruitment
- Planned Sample Size
- 118
- Recruitment Window Months
- 98
- Consent Approach
- Participants must provide signed and dated informed consent prior to participation. Only adult consent forms are provided (L1_ICF documents for adults). Informed consent materials are available in multiple languages (English, German, French, Italian, Spanish and Polish translations of protocol/ICF documents are present). No assent for minors is provided as inclusion is age 18-75.
Geography
- Total Number Of Sites
- 27
- Total Number Of Participants
- 118
Germany
- Earliest CTIS Part Ii Submission Date
- 10-04-2024
- Latest Decision Or Authorization Date
- 03-02-2026
- Processing Time Days
- 664
- Number Of Sites
- 10
- Number Of Participants
- 59
Sites
- Site Name
- University Medical Center Hamburg-Eppendorf
- Department Name
- Oncology, Hematology and Bone Marrow Transplantation & Laboratory of Radiology
- Principal Investigator Name
- Jana Käthe Striefler
- Principal Investigator Email
- j.striefler@uke.de
- Contact Person Name
- Jana Käthe Striefler
- Contact Person Email
- j.striefler@uke.de
- Site Name
- Universitaetsklinikum Frankfurt AöR
- Department Name
- Hamatologie, Onkologie
- Principal Investigator Name
- Marit Ahrens
- Principal Investigator Email
- m.ahrens@med.uni-frankfurt.de
- Contact Person Name
- Marit Ahrens
- Contact Person Email
- m.ahrens@med.uni-frankfurt.de
- Site Name
- Universitaetsklinikum Muenster AöR
- Department Name
- Medicine A
- Principal Investigator Name
- Christoph Schliemann
- Principal Investigator Email
- Christoph.Schliemann@ukmuenster.de
- Contact Person Name
- Christoph Schliemann
- Contact Person Email
- Christoph.Schliemann@ukmuenster.de
- Site Name
- HELIOS Klinikum Bad Saarow GmbH
- Department Name
- nternal Medicine and Hematology and Oncology
- Principal Investigator Name
- Daniel Pink
- Principal Investigator Email
- daniel.pink@helios-gesundheit.de
- Contact Person Name
- Daniel Pink
- Contact Person Email
- daniel.pink@helios-gesundheit.de
- Site Name
- Max Planck Institut Fuer Neurologische Forschung Mit Klaus Joachim Zuelch Laboratorien Der Max Planck Gesellschaft Und Der Medizinischen Fakultaet Der Universitaet Zu Koeln
- Department Name
- Oncology
- Principal Investigator Name
- Roland Ulrich
- Principal Investigator Email
- roland.ullrich@uk-koeln.de
- Contact Person Name
- Roland Ulrich
- Contact Person Email
- roland.ullrich@uk-koeln.de
- Site Name
- Klinikum rechts der Isar der TU Muenchen AöR
- Department Name
- Oncology
- Principal Investigator Name
- Krischan Braitsch
- Principal Investigator Email
- Krischan.Braitsch@mri.tum.de
- Contact Person Name
- Krischan Braitsch
- Contact Person Email
- Krischan.Braitsch@mri.tum.de
- Site Name
- Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
- Department Name
- Hämatologie und Medizinische Onkologie
- Principal Investigator Name
- Marius Fried
- Principal Investigator Email
- Marius.Fried@unimedizin-mainz.de
- Contact Person Name
- Marius Fried
- Contact Person Email
- Marius.Fried@unimedizin-mainz.de
- Site Name
- Charite Universitaetsmedizin Berlin KöR
- Department Name
- Hamatologie, Oncology, Tumor Immunology
- Principal Investigator Name
- Anne Floercken
- Principal Investigator Email
- anne.floercken@charite.de
- Contact Person Name
- Anne Floercken
- Contact Person Email
- anne.floercken@charite.de
- Site Name
- Universitaetsklinikum Duesseldorf AöR
- Department Name
- Medicine A
- Principal Investigator Name
- Judith Strapatsas
- Principal Investigator Email
- Judith.Strapatsas@med.uni-duesseldorf.de
- Contact Person Name
- Judith Strapatsas
- Contact Person Email
- Judith.Strapatsas@med.uni-duesseldorf.de
- Site Name
- Universitaetsklinikum Heidelberg AöR
- Department Name
- KLINIK FÜR HÄMATOLOGIE, ONKOLOGIE, RHEUMATOLOGIE
- Principal Investigator Name
- Gerlinde Egerer
- Principal Investigator Email
- Gerlinde.Egerer@med.uni-heidelberg.de
- Contact Person Name
- Gerlinde Egerer
- Contact Person Email
- Gerlinde.Egerer@med.uni-heidelberg.de
Spain
- Earliest CTIS Part Ii Submission Date
- 10-04-2024
- Latest Decision Or Authorization Date
- 09-02-2026
- Processing Time Days
- 670
- Number Of Sites
- 7
- Number Of Participants
- 34
Sites
- Site Name
- Hospital Universitario Fundacion Jimenez Diaz
- Department Name
- Medical Oncology
- Principal Investigator Name
- Javier Martin Broto
- Principal Investigator Email
- jmartin@atbsarc.org
- Contact Person Name
- Javier Martin Broto
- Contact Person Email
- jmartin@atbsarc.org
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Medical Oncology
- Principal Investigator Name
- Claudia Maria Valverde Morales
- Principal Investigator Email
- cvalverde@vhio.net
- Contact Person Name
- Claudia Maria Valverde Morales
- Contact Person Email
- cvalverde@vhio.net
- Site Name
- Hospital Universitario Virgen De Las Nieves
- Department Name
- Oncologia Medica
- Principal Investigator Name
- Lucía Castillo Portellano
- Principal Investigator Email
- luportellano@gmail.com
- Contact Person Name
- Lucía Castillo Portellano
- Contact Person Email
- luportellano@gmail.com
- Site Name
- Hospital Unviersitario Miguel Servet
- Department Name
- Oncologia Medica
- Principal Investigator Name
- Javier Martinez Trufero
- Principal Investigator Email
- jmtrufero@seom.org
- Contact Person Name
- Javier Martinez Trufero
- Contact Person Email
- jmtrufero@seom.org
- Site Name
- University Clinical Hospital Virgen De La Arrixaca
- Department Name
- Oncologia
- Principal Investigator Name
- Jerónimo Martínez García
- Principal Investigator Email
- jeronimo@seom.org
- Contact Person Name
- Jerónimo Martínez García
- Contact Person Email
- jeronimo@seom.org
- Site Name
- Hospital General Universitario Gregorio Maranon
- Department Name
- Medical Oncology
- Principal Investigator Name
- Rosa Maria Alvarez
- Principal Investigator Email
- rosa.alvarez.al@gmail.com
- Contact Person Name
- Rosa Maria Alvarez
- Contact Person Email
- rosa.alvarez.al@gmail.com
- Site Name
- Hospital Universitario Fundacion Jimenez Diaz (duplicate entry in listing?)
- Department Name
- Medical Oncology
- Principal Investigator Name
- Javier Martin Broto
- Principal Investigator Email
- jmartin@atbsarc.org
- Contact Person Name
- Javier Martin Broto
- Contact Person Email
- jmartin@atbsarc.org
France
- Earliest CTIS Part Ii Submission Date
- 10-04-2024
- Latest Decision Or Authorization Date
- 02-02-2026
- Processing Time Days
- 663
- Number Of Sites
- 5
- Number Of Participants
- 12
Sites
- Site Name
- Centre Leon Berard
- Department Name
- Medical Oncology
- Principal Investigator Name
- Jean-Yves Blay
- Principal Investigator Email
- Jean-Yves.Blay@lyon.unicancer.fr
- Contact Person Name
- Jean-Yves Blay
- Contact Person Email
- Jean-Yves.Blay@lyon.unicancer.fr
- Site Name
- Institut Gustave Roussy
- Department Name
- Medical Oncology
- Principal Investigator Name
- Axel Le Cesne
- Principal Investigator Email
- Axel.LECESNE@gustaveroussy.fr
- Contact Person Name
- Axel Le Cesne
- Contact Person Email
- Axel.LECESNE@gustaveroussy.fr
- Site Name
- Centre Antoine Lacassagne
- Department Name
- CLCC Unicancer
- Principal Investigator Name
- Agnès Ducoulombier
- Principal Investigator Email
- Agnes.DUCOULOMBIER@nice.unicancer.fr
- Contact Person Name
- Agnès Ducoulombier
- Contact Person Email
- Agnes.DUCOULOMBIER@nice.unicancer.fr
- Site Name
- Centr Georges Francois Leclerc
- Department Name
- Medical Oncology
- Principal Investigator Name
- Alice Hervieu
- Principal Investigator Email
- ahervieu@cgfl.fr
- Contact Person Name
- Alice Hervieu
- Contact Person Email
- ahervieu@cgfl.fr
- Site Name
- Institut Bergonie
- Department Name
- Medical Oncology
- Principal Investigator Name
- Antoine Italiano
- Principal Investigator Email
- A.Italiano@bordeaux.unicancer.fr
- Contact Person Name
- Antoine Italiano
- Contact Person Email
- A.Italiano@bordeaux.unicancer.fr
Poland
- Earliest CTIS Part Ii Submission Date
- 10-04-2024
- Latest Decision Or Authorization Date
- 08-02-2026
- Processing Time Days
- 669
- Number Of Sites
- 1
- Number Of Participants
- 6
Sites
- Site Name
- Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
- Department Name
- Oncology
- Principal Investigator Name
- Piotr Rutkowski
- Principal Investigator Email
- Piotr.Rutkowski@pib-nio.pl
- Contact Person Name
- Piotr Rutkowski
- Contact Person Email
- Piotr.Rutkowski@pib-nio.pl
Italy
- Earliest CTIS Part Ii Submission Date
- 10-04-2024
- Latest Decision Or Authorization Date
- 04-02-2026
- Processing Time Days
- 665
- Number Of Sites
- 4
- Number Of Participants
- 7
Sites
- Site Name
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Department Name
- Medical Oncology
- Principal Investigator Name
- Michela Quirino
- Principal Investigator Email
- michela.quirino@policlinicogemelli.it
- Contact Person Name
- Michela Quirino
- Contact Person Email
- michela.quirino@policlinicogemelli.it
- Site Name
- Azienda Ospedaliero-Universitaria San Luigi Gonzaga
- Department Name
- Medical Oncology
- Principal Investigator Name
- Lorenzo D'Ambrosio
- Principal Investigator Email
- lorenzo.dambrosio@unito.it
- Contact Person Name
- Lorenzo D'Ambrosio
- Contact Person Email
- lorenzo.dambrosio@unito.it
- Site Name
- Istituto Ortopedico Rizzoli
- Department Name
- Medical Oncology
- Principal Investigator Name
- Toni Ibrahim
- Principal Investigator Email
- toni.ibrahim@ior.it
- Contact Person Name
- Toni Ibrahim
- Contact Person Email
- toni.ibrahim@ior.it
- Site Name
- Istituto Di Candiolo Fondazione Del Piemonte Per Loncologia IRCCS
- Department Name
- Medical Oncology
- Principal Investigator Name
- Sandra Aliberti
- Principal Investigator Email
- sandra.aliberti@ircc.it
- Contact Person Name
- Sandra Aliberti
- Contact Person Email
- sandra.aliberti@ircc.it
Sponsor
Primary sponsor
- Full Name
- Philogen S.p.A.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- Italy
Third parties
- {"country":"Italy","full_name":"Opis S.r.l.","duties_or_roles":"Sponsor duties (code: 1)","organisation_type":"Pharmaceutical company"}
- {"country":"Spain","full_name":"Sofpromed Investigacion Clinica S.L.","duties_or_roles":"Sponsor duties (code: 1)","organisation_type":"Hospital/Clinic/Other health care facility"}
Investigational products
- Investigational Product Name
- Fibromun
- Active Substance
- ONFEKAFUSP ALFA
- Modality
- Other antibody
- Routes Of Administration
- INTRAVENOUS INFUSION
- Route
- INTRAVENOUS INFUSION
- Authorisation Status
- MIA number: aM 132/2019
- Orphan Designation
- Yes
- Frequency
- L19TNF (Fibromun) on Days 1, 3 and 5 every 3 weeks; maintenance (investigator discretion) L19TNF on Day 1 of every 21-day maintenance cycle until 18 months after study treatment start
- Maximum Dose
- 13 µg/Kg (max daily); max total 468 µg/Kg
- Investigational Product Name
- Doxorubicin 2 mg/ml Solution for Injection.
- Active Substance
- DOXORUBICIN HYDROCHLORIDE
- Modality
- Small molecule
- Routes Of Administration
- SOLUTION FOR INFUSION
- Route
- SOLUTION FOR INFUSION
- Authorisation Status
- Marketing authorisation: PL 00057/ 0970
- Frequency
- Doxorubicin on Day 1 every 3 weeks
- Maximum Dose
- 75 mg/m2 per administration (max daily); max total 450 mg/m2
- Combination Treatment
- Yes
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