An Open Label Phase 2 Study on Propranolol and Pembrolizumab in Advanced Angiosarcoma and Undifferentiated Pleomorphic Sarcoma - a Scandinavian Sarcoma Group Collaboration
The goal of this phase 2 clinical trial is to test efficacy and tolerability of combining propranolol and pembrolizumab in patients with advanced angiosarcoma or undifferentiated pleomorphic sarcoma. The main questions aims to answer: * Primary: determine the progression-free survival rate (PFSR) at 3 months Secondary: determine the objective response rate (ORR), duration of Response (DOR), Progression Free Survival (PFS), Overall Survival (OS). Ensure the safety and tolerability, Determine Quality of Life (QoL) • Exploratory: Characterize the TME Participants will be asked to ensure * Baseline biopsy and further optional biopsies * Treatment propranolol 40 mg BID and pembrolizumab 2 mg/kg Q3 weeks * Evaluation, blood counts, QoL and blood samples for biomarkers according to schedule
• 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 biomarker related 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:
• Absolute neutrophil count (ANC) ≥ 1 x 10⁹/L
• Platelet count ≥ 75 x 10⁹/L
• Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin ≤ 50 mmol/L)
• Aspartate transaminase (AST)/Alanine transaminase (ALT) ≤ 5 x ULN
• 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 \< 1 % per year during the treatment period and for at least 120 days after the treatment. Safe contraceptive methods for women are birth control pills, intrauterine device, contraceptive injection, contraceptive implant,contraceptive patch or contraceptive vaginal ring.
• Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year during the treatment period and for at least 120 days after the treatment.
• Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception