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Comparing L19TNF with Doxorubicin to Doxorubicin Alone for Advanced Soft Tissue Sarcoma

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

Phase 3 Interventional Philogen S.p.A. · NCT04650984

This study is testing if adding a new treatment called L19TNF to the standard drug doxorubicin can help people with advanced soft tissue sarcoma live longer without their cancer getting worse.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment102 (estimated)
Ages18 Years to 75 Years
SexAll
SponsorPhilogen S.p.A. Industry-sponsored
Drugs / interventionschemotherapy, radiation, doxorubicin
Locations28 sites (Bordeaux and 27 other locations)
Trial IDNCT04650984 on ClinicalTrials.gov

What this trial studies

This clinical trial is an open-label, randomized, controlled study designed to evaluate the efficacy of L19TNF in combination with doxorubicin compared to doxorubicin alone in patients with advanced or metastatic soft tissue sarcoma. A total of 102 patients will be randomly assigned to receive either standard doxorubicin treatment or the combination therapy. The primary goal is to assess progression-free survival rates between the two treatment arms. Safety assessments will also be conducted throughout the study to monitor adverse events.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with advanced unresectable or metastatic high-grade soft tissue sarcoma not suitable for curative surgery or radiotherapy.

Not a fit: Patients with specific types of sarcoma such as osteosarcoma, chondrosarcoma, or gastrointestinal stromal tumors will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve progression-free survival for patients with advanced soft tissue sarcoma.

How similar studies have performed: Other studies have shown promise in combining targeted therapies with traditional chemotherapy, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

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 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.

Where this trial is running

Bordeaux and 27 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Soft Tissue Sarcoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.