Informations générales (source: ClinicalTrials.gov)
A Phase III Study Comparing the Efficacy of the Combination of Doxorubicin and the Tumor-targeting Human Antibody-cytokine Fusion Protein L19TNF to Doxorubicin Alone as First-line Therapy in Patients With Advanced or Metastatic Soft Tissue Sarcoma
Interventional
Phase 3
Philogen S.p.A. (Voir sur ClinicalTrials)
novembre 2017
décembre 2025
13 août 2025
The present study is an open-label, randomized, controlled, two-arm multi-center study of
the efficacy of L19TNF treatment in combination with doxorubicin versus doxorubicin alone
in advanced or metastatic soft-tissue sarcoma patients.
In the study, 102 patients will be randomized in a 1:1 ratio to receive doxorubicin
treatment (Arm 1) or L19TNF treatment in combination with doxorubicin (Arm 2).
The primary objective of the trial is to evaluate if L19TNF in combination with
doxorubicin (Arm 2) given for unresectable or metastatic soft tissue sarcoma improves
efficacy measured as progression free survival, as compared to doxorubicin alone (Arm 1).
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Axel LE CESNE | 26/04/2024 06:46:12 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Antoine Lacassagne - Nice - France | Agnès Ducolombier | Contact (sur clinicalTrials) | |||
| Centre Georges François Leclerc - Dijon - France | Alice Hervieu | Contact (sur clinicalTrials) | |||
| Centre Léon Bérard - Lyon - France | Jean-Yves Blay | Contact (sur clinicalTrials) | |||
| Institut Bergonié - Bordeaux - France | Antoine Italiano | Contact (sur clinicalTrials) | |||
| Institut Claudius Regaud - Toulouse - France | Thibaud Valentin | Contact (sur clinicalTrials) | |||
| Institut Gustave Roussy - Villejuif - France | Axel Le Cesne | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
1. Patients aged 18-75 years.
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
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.
4. Life expectancy of at least 3 months.
5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
6. Documented negative test for HIV-HBV-HCV. For HBV serology: the determination of
HBsAg, anti-HBsAg-Ab and anti-HBCAg-Ab is required. In patients with serology
documenting previous exposure to HBV (i.e., anti-HBs Ab with no history of
vaccination and/or anti-HBc Ab), 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.
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.
8. Informed consent signed and dated to participate in the study.
9. Willingness and ability to comply with the scheduled visits, treatment plan,
laboratory tests and other study procedures.
1. Patients aged 18-75 years.
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
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.
4. Life expectancy of at least 3 months.
5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
6. Documented negative test for HIV-HBV-HCV. For HBV serology: the determination of
HBsAg, anti-HBsAg-Ab and anti-HBCAg-Ab is required. In patients with serology
documenting previous exposure to HBV (i.e., anti-HBs Ab with no history of
vaccination and/or anti-HBc Ab), 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.
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.
8. Informed consent signed and dated to participate in the study.
9. Willingness and ability to comply with the scheduled visits, treatment plan,
laboratory tests and other study procedures.
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 to therapy.
4. Known history of allergy to TNFα, anthracyclines or other intravenously administered
human proteins/peptides/antibodies.
5. Previous therapy with recombinant TNF.
6. Absolute neutrophil count (ANC) < 1.5 x 109/L, platelets < 100 x 109/L and
haemoglobin (Hb) < 9.0 g/dl.
7. Chronically impaired renal function or creatinine ≥ 2.0 x ULN.
8. Inadequate liver function (ALT, AST, ALP or total bilirubin ≥ 2.5 x ULN.
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.
10. History within the last year of acute or subacute coronary syndromes including
myocardial infarction, unstable or severe stable angina pectoris.
11. Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).
12. Clinically significant cardiac arrhythmias or requiring permanent medication.
13. Uncontrolled hypertension, despite optimal therapy.
14. Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine
classification).
15. Severe diabetic retinopathy such as severe non-proliferative retinopathy and
proliferative retinopathy.
16. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery)
within 4 weeks of administration of study treatment.
17. Pregnancy or breast-feeding.
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.
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.
20. Known active or latent tuberculosis (TB).
21. Concurrent malignancies other than Soft Tissue Sarcoma, unless the patient has been
disease-free for at least 2 years.
22. Growth factors or immunomodulatory agents within 7 days prior to the administration
of study treatment.
23. Serious, non-healing wound, ulcer or bone fracture.
24. Allergy to study medication or excipients in study medication.
25. Deep vein thrombosis, pulmonary embolism or other acute vascular events within 6
months.
26. Anticoagulation therapy with P2Y12 antagonists (e.g., clopidogrel, ticagrelor) and
vitamin K antagonists (e.g., phenprocoumon, warfarin).
27. Concurrent use of other anti-cancer treatments or agents other than study
medication.