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

April 5, 2024 updated by: Philogen S.p.A.

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
102

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • France
      • Bordeaux, France
        • Recruiting
        • Institut Bergonie
        • Contact:
          • Antoine Italiano
      • Dijon, France
        • Recruiting
        • Centre Georges Francois Leclerc
        • Contact:
          • Alice HERVIEU
      • Lyon, France
        • Recruiting
        • Centre Leon Berard
        • Contact:
          • Jean-Yves Blay
      • Nice, France
        • Recruiting
        • Centre Antoine Lacassagne
        • Contact:
          • Agnès Ducolombier
      • Toulouse, France
        • Not yet recruiting
        • Institut Claudius Regaud
        • Contact:
          • Thibaud Valentin
      • Villejuif, France
        • Not yet recruiting
        • Institut Gustave Roussy
        • Contact:
          • Axel Le Cesne
  • Germany
      • Bad Saarow, Germany, 15526
        • Recruiting
        • Helios Klinikum Bad Saarow
        • Contact:
          • Daniel Pink, Dr
      • Berlin, Germany
        • Recruiting
        • Charité- Universitätsmedizin Berlin
        • Contact:
          • Anne Floercken, PD Dr. med.
      • Düsseldorf, Germany
        • Not yet recruiting
        • Universitätsklinikum Düsseldorf
        • Contact:
          • Judith Strapatsas, PD Dr. med.
      • Frankfurt, Germany, 60590
        • Recruiting
        • Universitätsklinikum Frankfurt
        • Contact:
          • Marit Ahrens, MD
      • Hamburg, Germany
        • Recruiting
        • Universitätsklinik Hamburg-Eppendorf
        • Contact:
          • Jana Kaethe Striefler, PD Dr. med.
      • Heidelberg, Germany, D-69120
        • Recruiting
        • Heidelberg University Hospital
        • Contact:
          • Gerlinde Egerer, MD
      • Köln, Germany, 50937
        • Recruiting
        • Uniklinik Koln
        • Contact:
          • Roland Ulrich
      • Mainz, Germany
        • Recruiting
        • Universitätsmedizin der J.-G. Universität Mainz
        • Contact:
          • Marius Fried, PD Dr.
      • München,, Germany
        • Recruiting
        • Klinik rechts der Isar
        • Contact:
          • Judith Hecker, PD Dr. med
      • Münster, Germany, 48149
        • Recruiting
        • Universitaetsklinikum Muenster
        • Contact:
          • Christoph Schliemann, Prof. MD
  • Italy
      • Bologna, Italy
        • Recruiting
        • Bologna University, Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, Department of DIMES
        • Contact:
          • Emanuela Palmerini, MD
      • Orbassano, Italy, 10043
        • Not yet recruiting
        • AOU San Luigi Gonzaga
        • Contact:
          • Lorenzo D'Ambrosio, Dr.
      • Roma, Italy, 00168
        • Not yet recruiting
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
        • Contact:
          • Michela Quirino, Dr.
    • Torino
      • Candiolo, Torino, Italy
        • Recruiting
        • IRCCS Fondazione del Piemonte per l'Oncologia Istituto per la Ricerca e la Cura del Cancro di Candiolo
        • Contact:
          • Sandra Aliberti, Dr.
  • Poland
      • Gdynia, Poland
        • Not yet recruiting
        • Szpital Pomorski Im. PCK
        • Contact:
          • Joanna Pikiel
      • Warsaw, Poland, 02-781
        • Recruiting
        • Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie Warszawa
        • Contact:
          • Piotr Rutkowski, MD
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Hospital Universitari Vall d'Hebron
        • Contact:
          • Claudia Valverde Morales, Dr.
      • Granada, Spain
        • Recruiting
        • Hospital Universitario Virgen de Las Nieves
        • Contact:
          • Lucía Castillo Portellano
      • Madrid, Spain
        • Recruiting
        • Hospital General Universitario Gregorio Marañon
        • Contact:
          • Rosa María Álvarez, Dr.
      • Madrid, Spain, 28003
        • Recruiting
        • Fundación Jiménez Díaz
        • Contact:
          • Javier M Broto, MD
      • Zaragoza, Spain
        • Recruiting
        • Hospital Miguel Servet
        • Contact:
          • Javier Martinez Trufero, Dr.
    • Murcia
      • El Palmar, Murcia, Spain
        • Recruiting
        • Hospital Universitario Virgen de la Arrixaca
        • Contact:
          • Jeronimo Martinez Garcia, Dr.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Arm 1
Patients will receive 75 mg/m2 doxorubicin once every 3 weeks (reference treatment).
Drug: Doxorubicin
Patients will receive a fixed dose doxorubicin, administered as a 15 ± 5 minutes i.v. infusion.
Experimental: 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).
Drug: Doxorubicin
Patients will receive a fixed dose doxorubicin, administered as a 15 ± 5 minutes i.v. infusion.
Drug: Onfekafusp alfa
Patients will receive a fixed dose of L19TNF in combination with a fixed dose of doxorubicin.
Other Names:
  • L19TNF

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Median Progression free survival (mPFS)
Time Frame: From randomization up to week 72
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).
From randomization up to week 72

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
PFS rate
Time Frame: At 3, 6, 9, 12, 18 months after randomization
Progression Free Survival
At 3, 6, 9, 12, 18 months after randomization
Overall Response Rate (ORR)
Time Frame: At 3, 6, 9, 12, 18 months after randomization
Rate of Complete Response and Partial Response of L19TNF plus Doxorubicin treatment group (Arm 2) versus Doxorubicin alone (Arm 1).
At 3, 6, 9, 12, 18 months after randomization
Overall survival (OS)
Time Frame: At 12 months and 18 months after randomization
OS in the L19TNF plus Doxorubicin treatment group (Arm 2) versus Doxorubicin alone (Arm 1)
At 12 months and 18 months after randomization
Median Overall survival (mOS)
Time Frame: At 12 months and 18 months after randomization
mOS in the L19TNF plus Doxorubicin treatment group (Arm 2) versus Doxorubicin alone (Arm 1).
At 12 months and 18 months after randomization
Adverse Events
Time Frame: From week 1 up to week 72
Number of patients with adverse events (AEs) assessed on CTCAE v.4.03
From week 1 up to week 72
HAFA assessment
Time Frame: 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)
Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19TNF (Arm 2).
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Philogen S.p.A.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 29, 2017

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 25, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 25, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 3, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 8, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 5, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PH-L19TNFDOX2-03/16

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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