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Soft Tissue SarcomaPhase 2FLASHNCT04733183

Efficacy and Safety of L19TNF in Previously Treated Patients with Advanced Stage or Metastatic Soft-tissue Sarcoma

A Phase 2 study testing Dacarbazine and onfekafusp alfa in people with Soft Tissue Sarcoma, run by Philogen S.p.A. at 23 sites in 5 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

Open label, randomized, controlled phase II study preceded by a safety run-in part in subjects with advanced or metastatic soft-tissue sarcoma. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Soft Tissue Sarcoma
What is being tested?
Dacarbazine and onfekafusp alfa
Could I receive a placebo?
No, everyone receives an active treatment
How many people
98 participants
Where
23 sitesin 5 countries
Study dates
28 Aug 2020to Dec 2025
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female, 18 to 80 years of age.
  • Histologically or cytologically confirmed advanced unresectable or metastatic soft tissue sarcoma (STS), Grade 2 - 3 according to the FNLCC grading system. Participants with bone sarcomas including Ewing sarcoma, Kaposi's sarcoma and gastrointestinal stromal tumors (GIST) will be excluded.
  • Subjects who received at least two prior systemic therapies (e.g., anthracyclines, taxanes, ifosfamide, gemcitabine, trabectedin, pazopanib, eribulin) for advanced or metastatic disease including at least one prior therapy based on anthracyclines as monotherapy or in combination. Neoadjuvant and adjuvant therapies can be considered as a prior line of treatment if the time to recurrence from completion of treatment was ≤ 12 months. Previous therapy with anthracyclines is not compulsory in situations of contraindications to this class of drugs. All previous therapies must have completed ≥ 3 weeks (21 days) prior to study treatment start.
  • Evidence of disease progression after prior line of therapy for advanced or metastatic disease.
  • Patients must have at least one unidimensionally measurable lesion by computed tomography as defined by RECIST criteria v.1.1. If only one lesion is present at screening this lesion should not have been irradiated during previous treatments.
  • Life expectancy of at least 3 months in the judgment of the investigator.
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  • ECOG ≤ 2.
  • 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 (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.
  • 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 study administration of L19TNF and/or DTIC, 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 throughout the study from the screening to six months following the last administration of L19TNF and/or DTIC (e.g. condom with spermicidal gel). Double-barrier contraception is required.
  • Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
  • 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).

Who cannot join

  • Anti-cancer treatment with radiation therapy (with the exception of radiation of single lesions for palliative reasons, e.g. pain management which then are not taken as indicator lesions for iRECIST response), chemotherapy, targeted therapies, immunotherapy, hormones or other antitumor therapies within 3 weeks prior to study treatment start.
  • Subjects who participated in an investigational drug or device study within 3 weeks prior to study treatment start.
  • Previous treatment with TNF or L19TNF or DTIC.
  • Known history of allergy to intravenously administered human proteins/peptides/antibodies and any other constituent of the product.
  • Absolute neutrophil count (ANC) < 1.5 x 109/L, platelets < 100 x 109/L and hemoglobin (Hb) < 9.0 g/dl, with the exception of values lower than these due to cytologically or histologically proven marrow metastasis, which will not constitute exclusion criteria.
  • Chronically impaired renal function as expressed by creatinine clearance < 60 mL/min or serum creatinine > 1.5 ULN.
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  • Inadequate liver function (ALT or AST ≥ 3 x ULN or ALP or GGT ≥ 2.5 x ULN, or total bilirubin ≥ 1.5 x ULN). For patients with metastatic lesions in the liver ALT, AST, GGT or ALP ≥ 5 x ULN.
  • Any severe concomitant condition which in the opinion of investigators 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 cerebrovascular disease and/or 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.
  • Abnormalities observed during baseline ECG and echocardiogram investigations that are considered as clinically significant by the investigator.
  • Uncontrolled hypertension.
  • 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.
  • 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.
  • Protected adults (i.e., persons referred to as adults who are under legal protection measure or unable to express their consent) or persons under the protection of justice.

Trial locations and contacts

23 sites in 5 countries.

23 sites in 5 countries

France8 sites
  • Hopital Jean Minjoz

    Besançon, 25000

  • Institut Bergonié

    Bordeaux

  • Centre Jean Perrin

    Clermont-Ferrand, 63011

  • Centre Léon Bérard

    Lyon

  • Institut Paoli-Calmettes

    Marseille, 13009

  • Institut régional du Cancer de Montepellier - ICM Val d'Aurelle

    Montpellier, 34298

  • Institut Claudius Regaud

    Toulouse, 31059

  • Institut Gustave Roussy

    Villejuif

Other trials in France

Spain5 sites
  • Hospital Universitario Fundación Jiménez Díaz

    Madrid

  • Hospital Universitario Virgen de La Victoria

    Málaga

  • Hospital Universitario de Canarias

    San Cristóbal de La Laguna

  • Hospital Universitario Donostia

    San Sebastián

  • Hospital Clínico Universitario de Valencia

    Valencia

Other trials in Spain

Germany4 sites
  • Helios Klinikum Bad Saarow

    Bad Saarow

  • Helios Klinikum Berlin- Buch

    Berlin

  • Klinik rechts der Isar, TU München

    München

  • Münster University Hospital

    Münster, Münster, 48149

Other trials in Germany

Italy4 sites
  • IRCCS - Istituto Ortopedico Rizzoli

    Bologna

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

    Candiolo

  • AOU San Luigi Gonzaga

    Orbassano, 10043

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

    Roma, 00168

Other trials in Italy

Poland2 sites
  • Szpital Pomorski Im. PCK

    Gdynia

  • Maria Sklodowska Curie National Research Institute of Oncology

    Warsaw

Other trials in Poland

About this study

Official title: A Randomized Study to Investigate the Efficacy and Safety of the Tumor-targeting Human Antibody-cytokine Fusion Protein L19TNF in Previously Treated Patients with Advanced Stage or Metastatic Soft-tissue Sarcoma

Open label, randomized, controlled phase II study preceded by a safety run-in part in subjects with advanced or metastatic soft-tissue sarcoma.

Read the detailed description

Open label, randomized, controlled phase II study preceded by a safety run-in part in subjects with advanced or metastatic soft-tissue sarcoma.

  • Safety Run-in Part: Six (6) patients will be treated with 1000 mg/m2 dacarbazine (DTIC) on Day 1 every 3 weeks plus 13 µg/kg L19TNF on Days 1, 3 and 5 every 3 weeks to test for safety of the combination. Should unacceptable toxicities occur in ≥ 2 patients during an observation period from Day 1 to Day 21 (first cycle), enrollment will be stopped at this dose level and 6 patients will be treated sequentially with DTIC at 850 mg/m2 on Day 1 every 3 weeks plus 13 µg/kg L19TNF on Days 1, 3 and 5 every 3 weeks.
  • Tumor Activity Evaluation Part

Approximately 86 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 DTIC on Day 1 every 3 weeks plus L19TNF on Days 1, 3 and 5 every 3 weeks.
  • Arm 2: Patients will receive DTIC on Day 1 every 3 weeks. During the conduct of the study, detailed safety parameters will be routinely reviewed by the DSMB.
Being tested
Dacarbazine, onfekafusp alfa
Medical subject headings
Sarcoma

What participants receive

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

  • DacarbazineDrug

    Also called DTIC

    Dacarbazine (DTIC), 1000 mg/m2 or 850 mg/m2 on Day 1 of every 21-day cycle (based on results and DSMB evaluation in the safety run-in part of the study)

  • onfekafusp alfaDrug

    Also called L19TNF

    L19TNF, 13 μg/kg, on Day 1, 3, and 5 of every 21-day cycle for a maximum of 6 induction cycles. Patients experiencing apparent or real benefit with minimal or acceptable toxicity from the first 6 cycles of treatment, can receive, at investigator's discretion, maintenance treatment of 13 μg/kg, on Day 1 every 21-day

Study groups in NCT04733183
Study groupRoleWhat they receive
Arm1: DTIC + L19TNFExperimentalPatients will receive Dacarbazine (DTIC) on Day 1 and L19TNF on Days 1, 3 and 5 every 21 days.
Receives: Drug: Dacarbazine; Drug: onfekafusp alfa
Arm 2: DTICActive comparatorPatients will receive Dacarbazine (DTIC) on Day 1 every 21-day cycle .
Receives: Drug: Dacarbazine

What is being measured

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

  1. Progression-free survival (PFS)

    Progression-free survival (PFS) in according to RECIST v.1.1. The duration is defined beginning from randomization to progression or death from any cause.

    Measured: The PFS rate will be assessed at 3 months.

  2. Progression-free survival (PFS)

    Progression-free survival (PFS) in according to RECIST v.1.1. The duration is defined beginning from randomization to progression or death from any cause.

    Measured: The PFS rate will be assessed at 6 months.

  3. Progression-free survival (PFS)

    Progression-free survival (PFS) in according to RECIST v.1.1. The duration is defined beginning from randomization to progression or death from any cause.

    Measured: The PFS rate will be assessed at 9 months.

  4. Progression-free survival (PFS)

    Progression-free survival (PFS) in according to RECIST v.1.1. The duration is defined beginning from randomization to progression or death from any cause.

    Measured: The PFS rate will be assessed at 12 months.

Secondary outcomes (6)
  1. Overall Survival (OS)

    Overall Survival (OS) will be assessed for all randomized patients. The duration is defined beginning from randomization to death from any cause.

    Measured: The OS will be calculated at 12, 18, 24 and 36 months.

  2. Objective response rate (ORR)

    Objective response rate (ORR, consisting of CR plus PR; only the non-irradiated lesions are measured) according to RECIST v.1.1 between arms.

    Measured: The ORR rate will be assessed at 3, 6, 9, 12 months.

  3. Objective Response Rate (ORR)

    Objective Response Rate (ORR, consisting of iCR plus iPR; only the non-irradiated lesions are measured) according to iRECIST in Arm1.

    Measured: The ORR rate will be assessed at 3, 6, 9, 12 months.

  4. Adverse Events

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

    Measured: Time Frame: From week 1 up to week 52

  5. HAFA assessment

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

    Measured: At day 1 of week 1 and week 2; at day 1 from week 4 up to week 18; at week 22 (EoT)

  6. Quality of life (HRQol)

    Quality of life of L19TNF in combination with DTIC compared to DTIC alone as Health-related Quality of life (HRQol)

    Measured: EORTC Quality of Life Questionnaire C30 will be assessed baseline at 3, 6, 9 and 12 months and EOT visit (if not done already within 4 weeks prior)

Timeline

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

  1. First posted1 Feb 2021
  2. Study start28 Aug 2020
  3. Primary completionDec 2025 (estimated)
  4. Study completionDec 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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Safety Run in: Six (6) Patients will be treated with 1000 or 850 mg/m2 dacarbazine (DTIC) on Day 1 every three weeks plus 13 µg/kg L19TNF on Days 1, 3 and 5 every three weeks to test for safety of the combination as evaluated by an independent Data Safety Monitoring Board (DSMB). Tumor Activity Evaluation Part Arm 1: Patients will receive DTIC on Day 1 and L19TNF on Days 1, 3 and 5 every 3 weeks. Arm 2: Patients will receive DTIC on Day 1 every 3 weeks.
Masking
None (open label)
Enrolment
98 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04733183
Sponsor's protocol ID
PH-L19TNFSARC-03/18
Acronym
FLASH
Status last verified
Jan 2025
First submitted
22 Jan 2021
Last updated
27 Jan 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dacarbazine and onfekafusp alfa in people with Soft Tissue Sarcoma, run by Philogen S.p.A. at 23 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 12 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: under way, not looking for participants, as of the sponsor's last update on 27 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in France, Spain, Germany, 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: The PFS rate will be assessed at 3 months.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 27 Jan 2025.

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