Advanced Angiosarcoma and Undifferentiated Pleomorphic Sarcoma MedDRA version: 21.1 Level: PT Classification code 10002476 Term: Angiosarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10025552 Term: Malignant fibrous histiocytoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Department of Oncology, Herlev & Gentofte Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care • Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study • Histologically confirmed diagnosis of unresectable locally advanced or metastatic Angiosarcoma or Undifferentiated Pleomorphic Sarcoma, who has progressed/failed to provide clinical benefit on first line standard chemotherapy. • Age =18 years • Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of =2 at the time of enrollment. • Evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). • Available material from archived formalin-fixed paraffin-embedded tumor tissue obtained within 3 months of study enrollment for biomarkerrelated studies. If not sufficient or available, a newly obtained core or excisional biopsy of a tumor lesion may be performed. • Patients must have normal organ and marrow function as defined below: o Absolute neutrophil count (ANC) = 1 x 10?/L o Platelet count = 75 x 10?/L o Serum bilirubin = 1.5 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin = 50 mmol/L) o Aspartate transaminase (AST)/Alanine transaminase (ALT) = 5 x ULN o Serum creatinine = 1.5 x ULN or creatinine clearance (CrCl) = 40 mL/min (using the Cockcroft-Gault formula) • Women of childbearing potential (WOCBP): Agreement to use contraceptive methods with a failure rate of =65 years) no F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: • Have an anticipated life expectancy of 10 mg daily prednisone equivalents) or other immunosuppressive medications. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. • Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) • Allergies and Adverse Drug Reaction o History of allergy to study drug components o History of severe hypersensitivity reaction to any monoclonal antibody • WOCBP who are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the progression-free survival rate at 3 months ;Secondary Objective: 1.Determine the objective response rate (ORR) and duration of Response (DOR) 2. Determine Progression Free Survival 3. Determine Overall Survival, 4. Determine safety 5. Determine Quality of Life Exploratory: To explore the association between anti-tumor activity and specific biomarker measures in the tumor tissue and in peripheral blood ;Primary end point(s): PFS rate (Percentage of patients alive with CR, PR and SD according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)) at 3 months;Timepoint(s) of evaluation of this end point: Due to Simon Two-stage design the primary endpoint will be evaluated at the interim analyse after stage 1 (18 patients ) for each cohort and after conclusion of stage 2 (40 patients in total) for each cohort | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. ORR (Percentage of patients with CR and PR), including duration hereof using RECIST v 1.1 2. median PFS, using RECIST v 1.1 3. median OS 4. Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 5. The 30 item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ C30) questionnaire Exploratory: Characterize tumor cells, immune cell infiltrates, immune markers, vasculature, and markers of angiogenesis and hypoxia in the tumor microenvironment and blood in response to treatment. Measure change in immune cells and markers in TME and blood comparing baseline samples with on treatment samples.;Timepoint(s) of evaluation of this end point: Secondary endpoints are evaluated after conclusion of stage 2 (40 patients in total) for each cohort | — |
Countries
Denmark, Norway
Contacts
Public ContactCoordinating PI Niels Junker
Department of Oncology, Herlev & Gentofte Hospital
Outcome results
None listed