Bintrafusp alfa and Doxorubicin Hydrochloride in Treating Patients With Advanced Sarcoma.

Phase 1

Conditions: soft-tissue sarcoma
MedDRA version: 20.0Level: LLTClassification code 10039494Term: Sarcoma NOSSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2020-005703-39-FR

Lead Sponsor: Institut Bergonié

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 80

Inclusion Criteria

1.Histologically confirmed soft-tissue sarcoma with unknown translocation (including the following histologies but not limited to undifferentiated pleomorphic sarcomas, dedifferentiated liposaromas or leiomyosarcomas).
2.Metastatic or unresectable locally advanced disease,
3.No previous systemic treatment for advanced/metastatic disease,
4.For TLS status: available archived FFPE tumor tissue sample or tumor material newly obtained by biopsy.
5.Age = 18 years,
6.ECOG = 1,
7.Life expectancy > 3 months,
8.Patients must have measurable disease defined as per RECIST v1.1,
9.Patient must comply with the collection of tumor biopsies and biomarkers study. Tumors must be accessible for biopsy,
10.Adequate hematological, renal, metabolic and hepatic function:
a)Hemoglobin = 9 g/dl (patients may not have received prior red blood cell transfusion in the last 30 days); absolute neutrophil count = 1.5 G/l, and platelet count = 100 G/l.
b)Alanine aminotransferase, aspartate aminotransferase = 1.5 x ULN (= 5 in case of extensive liver involvement) and alkaline phosphatase = 2.5 x ULN
c)Total bilirubin = ULN (= 3 in case of liver involvement)
d)Albumin = 30 g/l
e)Creatinine level = 1.5 x ULN or calculated creatinine clearance = 40 ml/min (according to Cockroft Gault formula)
f)INR, PT = 1.5 x ULN and aPTT = 1.5 x ULN.
11.Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization.
12.Both women and men must agree to use a highly effective method of contraception throughout the treatment period and for at least two months after discontinuation of treatment for women and four months for men.
13.No prior or concurrent malignant disease diagnosed or treated in the last 3 years except for a. Superficial/non-invasive bladder cancer, or basal or squamous cell carcinoma in situ treated with curative intent; b. endoscopically resected GI cancers limited to the mucosal layer without recurrence in > 1 year,
14.Recovery to grade = 1 from any adverse event derived from previous treatment (excluding alopecia and vitiligo of any grade and non-painful peripheral neuropathy grade = 2) according to the NCI-CTCAE, version 5.0,
15.Voluntarily signed and dated written informed consent prior to any study specific procedure,
16.Patients with a social security in compliance with the French law.
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 56
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24

Exclusion Criteria

1.Previous treatment with doxorubicin, daunorubicin, epirubicin, idarubicin and/or any other anthracyclines or anthracediones at the maximum cumulative dose or any approved or investigational treatment targeting PD1, PD-L1 or TGFB1,
2.Known central nervous system malignancy,
3.Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding,
4.Participation to a study involving a medical or therapeutic intervention in the last 30 days,
5.Previous enrolment in the present study,
6.Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons,
7.Known hypersensitivity to any involved study drug or any of its formulation components,
8. Any history of anaphylaxis, or recent, within 5 months, history of uncontrollable asthma,
9.Individuals deprived of liberty or placed under legal guardianship,
10.Any of the following cardiac criteria:
a)Mean QTcF = 470 msec, obtained from three consecutive ECGs,
b)Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG,
c)LVEF = 50% per CTCAE v5
d)Any factors increasing the risk of QTc prolongation or arrhythmic events ,
e)Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable angina pectoris, uncontrolled hypertension, congestive heart failure NYHA Grade =2, ventricular arrhythmias requiring continuous therapy, supraventricular arrhythmias including atrial fibrillation, which are uncontrolled, haemorrhagic or thrombotic stroke, including transient ischaemic attacks, cerebral vascular accident/stroke or any other central nervous system bleeding
11.Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
12.History of bleeding diathesis or recent major bleeding event (i.e. Grade = 2 bleeding events within 30 days prior to treatment,
13.Prior organ transplantation including allogenic stem-cell transplantation, except transplants that do not require immunosuppression,
14.Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection requiring systemic therapy, drug-induced interstitial lung disease (ILD) or subject has had a history of drug-induced pneumonitis that has required oral or IV steroids, and/or other diseases, which in the opinion of the investigator might impair the subject’s tolerance for the study or ability to consistently participate in study procedures,
15.Active infection including tuberculosis,
16.Has known active hepatitis B or hepatitis C,
17.Has a known history of HIV infection,
18.Receipt of live attenuated vaccine within 30 days prior to the first dose of treatment. ,
19.Patients with current or history of deep vein thrombosis within 6 months prior to randomization,
20.Any contraindication to biopsy for the research,
21.Any other contraindication to Doxorubicin administration,
22.Patients with oral anticoagulation therapy based on Vitamin K antagonist.
23.Prior mediastinal radiation.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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