A study to investigate the efficacy and safety of L19TNF in previously treated patients with advanced stage or metastatic soft-tissue sarcoma

Phase 1

• Conditions: nresectable and/or metastatic soft-tissue sarcoma after failure of at least two prior systemic therapy regimens; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-004104-19-IT
• Lead Sponsor: PHILOGEN S.P.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-30
• Last Update Posted: 6 December 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 98

Inclusion Criteria

- Male or female, 18 to 80 years of age
- Histologically or cytologically confirmed advanced unresectable or metastatic soft tissue sarcoma, grade 2 - 3 according to the FNCLCC 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 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
- ECOG = 2
- Documented negative test for HIV-HBV-HCV.
- 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 drug administration, 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). Male patients: Male subjects able to father children must agree to use two acceptable methods of contraception throughout the study (e.g. condom with spermicidal gel).
- 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 74
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24

Exclusion Criteria

- 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.
- 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
- Concurrent therapy with anticoagulants at full therapeutic dose
- Concurrent use of other anti-cancer treatments or agents other than study medication

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified