AzTrials
AzTrials

Soft Tissue SarcomaPhase 3FIBROSARCNCT04650984

A Study Comparing the Efficacy of L19TNF+Doxorubicin vs Doxorubicin Alone as First-line Therapy in Patients With Advanced or Metastatic Soft Tissue Sarcoma

A Phase 3 study testing Onfekafusp alfa and Doxorubicin in people with Soft Tissue Sarcoma, run by Philogen S.p.A. at 28 sites in 5 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Soft Tissue Sarcoma
What is being tested?
Onfekafusp alfa and Doxorubicin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
102 participants
Where
28 sitesin 5 countries
Study dates
29 Nov 2017to 31 Dec 2025
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients aged 18-75 years.
  • 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
  • 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.
  • Life expectancy of at least 3 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
  • 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.
Show all 9Show fewer
  • 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.
  • 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.

Who cannot join

  • Prior therapy (except surgery and radiation) for unresectable or metastatic malignant soft tissue sarcoma.
  • Previous treatment with anthracycline-containing chemotherapy.
  • Radiotherapy within 4 weeks prior to therapy.
  • Known history of allergy to TNFα, anthracyclines or other intravenously administered human proteins/peptides/antibodies.
  • Previous therapy with recombinant TNF.
  • Absolute neutrophil count (ANC) < 1.5 x 109/L, platelets < 100 x 109/L and haemoglobin (Hb) < 9.0 g/dl.
Show all 27Show fewer
  • Chronically impaired renal function or creatinine ≥ 2.0 x ULN.
  • Inadequate liver function (ALT, AST, ALP or total bilirubin ≥ 2.5 x ULN.
  • Any severe concomitant condition which makes it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol.
  • History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
  • Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).
  • Clinically significant cardiac arrhythmias or requiring permanent medication.
  • Uncontrolled hypertension, despite optimal therapy.
  • Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine classification).
  • Severe diabetic retinopathy such as severe non-proliferative retinopathy and proliferative retinopathy.
  • Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery) within 4 weeks of administration of study treatment.
  • Pregnancy or breast-feeding.
  • 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.
  • 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.
  • Known active or latent tuberculosis (TB).
  • Concurrent malignancies other than Soft Tissue Sarcoma, unless the patient has been disease-free for at least 2 years.
  • Growth factors or immunomodulatory agents within 7 days prior to the administration of study treatment.
  • Serious, non-healing wound, ulcer or bone fracture.
  • Allergy to study medication or excipients in study medication.
  • Deep vein thrombosis, pulmonary embolism or other acute vascular events within 6 months.
  • Anticoagulation therapy with P2Y12 antagonists (e.g., clopidogrel, ticagrelor) and vitamin K antagonists (e.g., phenprocoumon, warfarin).
  • Concurrent use of other anti-cancer treatments or agents other than study medication.

Trial locations and contacts

28 sites in 5 countries.

Teresa Hemmerle, PhD contact

+39 0577 17816

regulatory@philogen.com

Marco Taras, Biologist contact

regulatory@philogen.com

28 sites in 5 countries

Germany10 sites, 10 recruiting

  • Helios Klinikum Bad Saarow

    Bad Saarow, 15526

    Daniel Pink, Dr

    Recruiting

  • Charité- Universitätsmedizin Berlin

    Berlin

    Anne Floercken, PD Dr. med.

    Recruiting

  • Uniklinik Köln

    Cologne, 50937

    Roland Ulrich

    Recruiting

  • Universitätsklinikum Düsseldorf

    Düsseldorf

    Judith Strapatsas, PD Dr. med.

    Not yet recruiting

  • Universitätsklinikum Frankfurt

    Frankfurt, 60590

    Marit Ahrens, MD

    Recruiting

  • Universitätsklinik Hamburg-Eppendorf

    Hamburg

    Jana Kaethe Striefler, PD Dr. med.

    Recruiting

  • Heidelberg University Hospital

    Heidelberg, D-69120

    Gerlinde Egerer, MD

    Recruiting

  • Universitätsmedizin der J.-G. Universität Mainz

    Mainz

    Marius Fried, PD Dr.

    Recruiting

  • Klinik rechts der Isar

    München

    Judith Hecker, PD Dr. med

    Recruiting

  • Universitaetsklinikum Muenster

    Münster, 48149

    Christoph Schliemann, Prof. MD

    Recruiting

Other trials in Germany

France6 sites, 6 recruiting

  • Institut Bergonié

    Bordeaux

    Antoine Italiano

    Recruiting

  • Centre Georges François Leclerc

    Dijon

    Alice Hervieu

    Recruiting

  • Centre Léon Bérard

    Lyon

    Jean-Yves Blay

    Recruiting

  • Centre Antoine Lacassagne

    Nice

    Agnès Ducolombier

    Recruiting

  • Institut Claudius Regaud

    Toulouse

    Thibaud Valentin

    Not yet recruiting

  • Institut Gustave Roussy

    Villejuif

    Axel Le Cesne

    Not yet recruiting

Other trials in France

Spain6 sites, 6 recruiting

  • Hospital Universitari Vall d'Hebron

    Barcelona

    Claudia Valverde Morales, Dr.

    Recruiting

  • Hospital Universitario Virgen de la Arrixaca

    El Palmar, Murcia

    Jeronimo Martinez Garcia, Dr.

    Recruiting

  • Hospital Universitario Virgen de las Nieves

    Granada

    Lucía Castillo Portellano

    Recruiting

  • Fundación Jiménez Díaz

    Madrid, 28003

    Javier M Broto, MD

    Recruiting

  • Hospital General Universitario Gregorio Marañón

    Madrid

    Rosa María Álvarez, Dr.

    Recruiting

  • Hospital Miguel Servet

    Zaragoza

    Javier Martinez Trufero, Dr.

    Recruiting

Other trials in Spain

Italy4 sites, 4 recruiting

  • Bologna University, Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, Department of DIMES

    Bologna

    Emanuela Palmerini, MD

    Recruiting

  • IRCCS Fondazione del Piemonte per l'Oncologia Istituto per la Ricerca e la Cura del Cancro di Candiolo

    Candiolo, Torino

    Sandra Aliberti, Dr.

    Recruiting

  • AOU San Luigi Gonzaga

    Orbassano, 10043

    Lorenzo D'Ambrosio, Dr.

    Not yet recruiting

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

    Roma, 00168

    Michela Quirino, Dr.

    Not yet recruiting

Other trials in Italy

Poland2 sites, 2 recruiting

  • Szpital Pomorski Im. PCK

    Gdynia

    Joanna Pikiel

    Not yet recruiting

  • Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie Warszawa

    Warsaw, 02-781

    Piotr Rutkowski, MD

    Recruiting

Other trials in Poland

About this study

Official title: 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

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).

Read the detailed description

Phase III, open label, randomized, controlled study in subjects with advanced or metastatic soft tissue sarcoma. In the study, 102 patients will be enrolled and parallel assigned in a 1:1 fashion to one of two different arms, as follows:

  • ARM 1: Patients will receive 75 mg/m2 doxorubicin once every 3 weeks (reference treatment).
  • ARM 2: Patients will receive 13 µg/kg L19TNF on days 1, 3 and 5 every 3 weeks in combination with 60 mg/m2 doxorubicin (once every 3 weeks).

Anti-cancer activity will be assessed every 6 weeks during therapy and every 12 weeks thereafter. Median PFS, PFS rates at 3, 6, 9, 12 and 18 months, mOS, OS rate at 12 and 18 months and ORR will be calculated.

Safety assessment will be performed on an ongoing basis during study participation, including standard laboratory assessments. The incidence of AEs will be summarized by severity in all patients with at least one study drug intake.

Being tested
Onfekafusp alfa, Doxorubicin
Medical subject headings
Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Onfekafusp alfaDrug

    Also called L19TNF

    Patients will receive a fixed dose of L19TNF in combination with a fixed dose of doxorubicin.

  • DoxorubicinDrug

    Patients will receive a fixed dose doxorubicin, administered as a 15 ± 5 minutes i.v. infusion.

Study groups in NCT04650984
Study groupRoleWhat they receive
Arm 1Active comparatorPatients will receive 75 mg/m2 doxorubicin once every 3 weeks (reference treatment).
Receives: Drug: Doxorubicin
Arm 2ExperimentalPatients will receive 13 µg/kg L19TNF on days 1, 3 and 5 every 3 weeks in combination with 60 mg/m2 doxorubicin (once every 3 weeks).
Receives: Drug: Onfekafusp alfa; Drug: Doxorubicin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Median Progression free survival (mPFS)

    Progression-free survival PFS in a time-to-event analysis in the L19TNF plus Doxorubicin control group (Arm 2) versus the Doxorubicin alone treatment group (Arm 1).

    Measured: From randomization up to week 72

Secondary outcomes (6)

  1. PFS rate

    Progression Free Survival

    Measured: At 3, 6, 9, 12, 18 months after randomization

  2. Overall Response Rate (ORR)

    Rate of Complete Response and Partial Response of L19TNF plus Doxorubicin treatment group (Arm 2) versus Doxorubicin alone (Arm 1).

    Measured: At 3, 6, 9, 12, 18 months after randomization

  3. Overall survival (OS)

    OS in the L19TNF plus Doxorubicin treatment group (Arm 2) versus Doxorubicin alone (Arm 1)

    Measured: At 12 months and 18 months after randomization

  4. Median Overall survival (mOS)

    mOS in the L19TNF plus Doxorubicin treatment group (Arm 2) versus Doxorubicin alone (Arm 1).

    Measured: At 12 months and 18 months after randomization

  5. Adverse Events

    Number of patients with adverse events (AEs) assessed on CTCAE v.4.03

    Measured: From week 1 up to week 72

  6. HAFA assessment

    Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19TNF (Arm 2).

    Measured: At day 1 of week 1 and week 2; at day 1 from week 4 up to week 18, every 3 weeks; at week 22-23 (EoT); at week 23-24 (first follow-up visit)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Dec 2020
  2. Study start29 Nov 2017
  3. Primary completion31 Dec 2025 (estimated)
  4. Study completion31 Dec 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
102 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04650984
Sponsor's protocol ID
PH-L19TNFDOX2-03/16
Acronym
FIBROSARC
Status last verified
Apr 2024
First submitted
25 Nov 2020
Last updated
8 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Onfekafusp alfa and Doxorubicin in people with Soft Tissue Sarcoma, run by Philogen S.p.A. at 28 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 8 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in Germany, France, Spain, Italy, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Teresa Hemmerle, PhD (+39 0577 17816, regulatory@philogen.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Median Progression free survival (mPFS) (time frame: From randomization up to week 72). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04650984.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2024; AzTrials last refreshed its copy on 8 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in