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

NCT ID: NCT04650984

Last Updated: 2024-04-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

102 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-11-29

Study Completion Date

2025-12-31

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Soft Tissue Sarcoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1

Patients will receive 75 mg/m2 doxorubicin once every 3 weeks (reference treatment).

Group Type ACTIVE_COMPARATOR

Doxorubicin

Intervention Type DRUG

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

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).

Group Type EXPERIMENTAL

Onfekafusp alfa

Intervention Type DRUG

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

Doxorubicin

Intervention Type DRUG

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

Interventions

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Onfekafusp alfa

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

Intervention Type DRUG

Doxorubicin

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

Intervention Type DRUG

Other Intervention Names

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L19TNF

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Philogen S.p.A.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Institut Bergonié

Bordeaux, , France

Site Status RECRUITING

Centre Georges François Leclerc

Dijon, , France

Site Status RECRUITING

Centre Léon Bérard

Lyon, , France

Site Status RECRUITING

Centre Antoine Lacassagne

Nice, , France

Site Status RECRUITING

Institut Claudius Regaud

Toulouse, , France

Site Status NOT_YET_RECRUITING

Institut Gustave Roussy

Villejuif, , France

Site Status NOT_YET_RECRUITING

Helios Klinikum Bad Saarow

Bad Saarow, , Germany

Site Status RECRUITING

Charité- Universitätsmedizin Berlin

Berlin, , Germany

Site Status RECRUITING

Uniklinik Köln

Cologne, , Germany

Site Status RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Frankfurt

Frankfurt, , Germany

Site Status RECRUITING

Universitätsklinik Hamburg-Eppendorf

Hamburg, , Germany

Site Status RECRUITING

Heidelberg University Hospital

Heidelberg, , Germany

Site Status RECRUITING

Universitätsmedizin der J.-G. Universität Mainz

Mainz, , Germany

Site Status RECRUITING

Klinik rechts der Isar

München, , Germany

Site Status RECRUITING

Universitaetsklinikum Muenster

Münster, , Germany

Site Status RECRUITING

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

Candiolo, Torino, Italy

Site Status RECRUITING

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

Bologna, , Italy

Site Status RECRUITING

AOU San Luigi Gonzaga

Orbassano, , Italy

Site Status NOT_YET_RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, , Italy

Site Status NOT_YET_RECRUITING

Szpital Pomorski Im. PCK

Gdynia, , Poland

Site Status NOT_YET_RECRUITING

Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie Warszawa

Warsaw, , Poland

Site Status RECRUITING

Hospital Universitario Virgen de la Arrixaca

El Palmar, Murcia, Spain

Site Status RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario Virgen de las Nieves

Granada, , Spain

Site Status RECRUITING

Fundación Jiménez Díaz

Madrid, , Spain

Site Status RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Site Status RECRUITING

Hospital Miguel Servet

Zaragoza, , Spain

Site Status RECRUITING

Countries

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France Germany Italy Poland Spain

Central Contacts

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Teresa Hemmerle, PhD

Role: CONTACT

+39 0577 17816

Marco Taras, Biologist

Role: CONTACT

Facility Contacts

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Antoine Italiano

Role: primary

Alice Hervieu

Role: primary

Jean-Yves Blay

Role: primary

Agnès Ducolombier

Role: primary

Thibaud Valentin

Role: primary

Axel Le Cesne

Role: primary

Daniel Pink, Dr

Role: primary

Anne Floercken, PD Dr. med.

Role: primary

Roland Ulrich

Role: primary

Judith Strapatsas, PD Dr. med.

Role: primary

Marit Ahrens, MD

Role: primary

Jana Kaethe Striefler, PD Dr. med.

Role: primary

Gerlinde Egerer, MD

Role: primary

Marius Fried, PD Dr.

Role: primary

Judith Hecker, PD Dr. med

Role: primary

Christoph Schliemann, Prof. MD

Role: primary

Sandra Aliberti, Dr.

Role: primary

Emanuela Palmerini, MD

Role: primary

Lorenzo D'Ambrosio, Dr.

Role: primary

Michela Quirino, Dr.

Role: primary

Joanna Pikiel

Role: primary

Piotr Rutkowski, MD

Role: primary

Jeronimo Martinez Garcia, Dr.

Role: primary

Claudia Valverde Morales, Dr.

Role: primary

Lucía Castillo Portellano

Role: primary

Javier M Broto, MD

Role: primary

Rosa María Álvarez, Dr.

Role: primary

Javier Martinez Trufero, Dr.

Role: primary

Other Identifiers

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PH-L19TNFDOX2-03/16

Identifier Type: -

Identifier Source: org_study_id

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