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

NCT04650984 | Recruiting Phase 3 DMC

• 1 other identifier: PH-L19TNFDOX2-03/16
• Study Type: interventional
• Target: 102
• Locations: 5 countries
• Sites: 28

Brief 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. 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).

Conditions

Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (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).

  From randomization up to week 72

Secondary Outcomes (6)

• PFS rate

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

• Overall Response Rate (ORR)

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

• Overall survival (OS)

  At 12 months and 18 months after randomization

• Median Overall survival (mOS)

  At 12 months and 18 months after randomization

• Adverse Events

  From week 1 up to week 72

Study Arms (2)

Arm 1

ACTIVE COMPARATOR

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

Drug: Doxorubicin

Arm 2

EXPERIMENTAL

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: Onfekafusp alfa; Drug: Doxorubicin

Interventions

Onfekafusp alfa DRUG

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

Also known as: L19TNF

Arm 2

Doxorubicin DRUG

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

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (28)

Institut Bergonié

Bordeaux, France

RECRUITING

Centre Georges François Leclerc

Dijon, France

RECRUITING

Centre Léon Bérard

Lyon, France

RECRUITING

Centre Antoine Lacassagne

Nice, France

RECRUITING

Institut Claudius Regaud

Toulouse, France

NOT YET RECRUITING

Institut Gustave Roussy

Villejuif, France

NOT YET RECRUITING

Helios Klinikum Bad Saarow

Bad Saarow, 15526, Germany

RECRUITING

Charité- Universitätsmedizin Berlin

Berlin, Germany

RECRUITING

Uniklinik Köln

Cologne, 50937, Germany

RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, Germany

NOT YET RECRUITING

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

RECRUITING

Universitätsklinik Hamburg-Eppendorf

Hamburg, Germany

RECRUITING

Heidelberg University Hospital

Heidelberg, D-69120, Germany

RECRUITING

Universitätsmedizin der J.-G. Universität Mainz

Mainz, Germany

RECRUITING

Klinik rechts der Isar

München, Germany

RECRUITING

Universitaetsklinikum Muenster

Münster, 48149, Germany

RECRUITING

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

Candiolo, Torino, Italy

RECRUITING

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

Bologna, Italy

RECRUITING

AOU San Luigi Gonzaga

Orbassano, 10043, Italy

NOT YET RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

NOT YET RECRUITING

Szpital Pomorski Im. PCK

Gdynia, Poland

NOT YET RECRUITING

Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie Warszawa

Warsaw, 02-781, Poland

RECRUITING

Hospital Universitario Virgen de la Arrixaca

El Palmar, Murcia, Spain

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, Spain

RECRUITING

Hospital Universitario Virgen de las Nieves

Granada, Spain

RECRUITING

Fundación Jiménez Díaz

Madrid, 28003, Spain

RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, Spain

RECRUITING

Hospital Miguel Servet

Zaragoza, Spain

RECRUITING

MeSH Terms

Conditions

Sarcoma

Interventions

Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Central Study Contacts

Teresa Hemmerle, PhD

CONTACT

+39 0577 17816; regulatory@philogen.com

Marco Taras, Biologist

CONTACT

regulatory@philogen.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2020
• First Posted: December 3, 2020
• Study Start: November 29, 2017
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: April 8, 2024

Record last verified: 2024-04

Locations

DE (10); PL (2); FR (6); ES (6); IT (4)