Bintrafusp Alfa and Doxorubicin Hydrochloride in Treating Patients With Advanced Sarcoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorInstitut Bergonié
About this trial
This study encompasses two multicenter, prospective, open-labeled, 2-arm, non-comparative randomized phase II trials to assess the antitumor activity of bintrafusp alfa in association with doxorubicin
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically confirmed soft-tissue sarcoma with unknown translocation (including the following histologies but not limited to undifferentiated pleomorphic sarcomas, dedifferentiated liposaromas or leiomyosarcomas). Diagnosis must be reviewed or confirmed by the RRePS Network (Réseau de référence en pathologie des sarcomes et des viscères) as recommended by the French NCI (Institut National du Cancer, Inca).
Metastatic or unresectable locally advanced disease,
No previous systemic treatment for advanced/metastatic disease,
For TLS status: available archived FFPE (Formalin-Fixed Paraffin-Embedded) tumor tissue sample or tumor material newly obtained by biopsy. Except if TLS analysis have been already performed by Biopathological platform at Bergonié Institute, presence or absence of TLS should be confirmed by central review based on FFPE tumor tissue sample (archived or newly obtained by biopsy for research purpose),
Disqualifiers
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,
Known central nervous system malignancy (CNS),
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,
Participation to a study involving a medical or therapeutic intervention in the last 30 days,
Trial design
Design model
Parallel
Treatments tested in this trial
Bintrafusp alfa
DrugBintrafusp alfa will be administered by intravenous infusion on day 1 every 3 weeks at a fixed dose of 2400 mg.
Doxorubicin
DrugDoxorubicin will be administered by intravenous infusion on day 1 every 3 weeks at a fixed dose of 75 mg/m² for a maximum of 6 cycles
Treatment groups
80 Participants
are divided into 4 treatment groupsGroup A: Experimental Arm A: treatment by bintrafusp alfa combined with doxorubicinExperimental treatment 2 interventions
Group B: Standard Arm B: treatment by doxorubicinOther 1 intervention
Group C: Experimental Arm C: treatment by bintrafusp alfa combined with doxorubicinExperimental treatment 2 interventions
Group D: Standard Arm D: treatment by doxorubicinOther 1 intervention
Trial outcomes
Primary outcomes
1
Assessment of the antitumor activity of combined administration of standard doxorubicin and double immune modulation with Bintrafusp alfa in terms of 6-month progression-free rate, in STS patients with an inflammed tumor
Antitumor activity will be assessed in terms of 6-month progression-free rate and is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST v1.1.
Time frame
6 months2
Assessment of the antitumor activity of combined administration of standard doxorubicin and double immune modulation with Bintrafusp alfa in terms of 6-month progression-free rate, in STS patients with a cold tumor
Antitumor activity will be assessed in terms of 6-month progression-free rate and is defined as the rate of complete or partial response (CR, PR) or stable disease (SD), as per RECIST v1.1.
Time frame
6 monthsSecondary outcomes
1
6-month objective response rate (ORR) independently for patients with an inflammed tumor
Objective response is defined as complete response (CR) or partial response (PR) as per adapted RECIST v1.1.
Time frame
6 months2
6-month objective response rate (ORR) independently for patients with a cold tumor
Objective response is defined as complete response (CR) or partial response (PR) as per adapted RECIST v1.1.
Time frame
6 months3
Best overall response for patients with an inflammed tumor
Best overall response is defined as the best reponse across all time points (RECIST v1.1). The best overall response rate is determined once all the data for the patient is known
Time frame
throughout the treatment period, an expected average of 6 months4
Best overall response for patients with a cold tumor
Best overall response is defined as the best reponse across all time points (RECIST v1.1). The best overall response rate is determined once all the data for the patient is known
Time frame
throughout the treatment period, an expected average of 6 monthsOther outcomes
1
Tumor immune cells levels independently for each population
Levels of immune cells (CD4, CD8, PDL1)in tumor will be measured by immunohistochemistry
Time frame
baseline, cycle 2 day 1, and progression (each cycle is 21 days)2
Blood cytokines levels independently for each population
Levels of cytokines (tryptophane, interleukine) in blood will be measured by ELISA
Time frame
baseline, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days)3
Blood lymphocytes levels independently for each population
Levels of fixed PBMC (peripheral blood mononucear cells) in blood will be measured by flow cytometry
Time frame
baseline, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days)4
Blood kynurenine levels independently for each population
Levels of kynurenine in blood will be measured by ELISA
Time frame
baseline, cycle 2 day 1, cycle 3 day 1 and progression (each cycle is 21 days)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Institut Bergonié
Lead sponsor
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Collaborator
Source ClinicalTrials.gov