Propranolol hydrochloride for Angiosarcoma | Undifferentiated pleomorphic sarcoma

Inclusion criteria

• {"criterion_text":"- 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\n- Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin ≤ 50 mmol/L)\n- Aspartate transaminase (AST)/Alanine transaminase (ALT) ≤ 5 x ULN\n- Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (using the Cockcroft-Gault formula)\n- 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.\n- 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.\n- Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception\n- Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study\n- 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.\n- Age ≥18 years\n- Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of ≤2 at the time of enrollment.\n- Evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).\n- 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.\n- Absolute neutrophil count (ANC) ≥ 1 x 10⁹/L\n- Platelet count ≥ 75 x 10⁹/L"}

Exclusion criteria

• {"criterion_text":"- Have an anticipated life expectancy of <3 months.\n- Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results\n- Participants with active, known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll\n- Participants with a condition requiring systemic treatment with either corticosteroids (>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\n- Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)\n- History of allergy to study drug components\n- History of severe hypersensitivity reaction to any monoclonal antibody\n- WOCBP who are pregnant or breastfeeding\n- Moderate to severe degree of bronchial asthma or chronic obstructive pulmonary disease.\n- Acute or non-stable congestive heart failure\n- Any other condition listed as contraindication for treatment with propranolol according to SPC\n- Have received any previous systemic therapy targeting the PD-1/PDL-1 signaling pathway or other immune checkpoint inhibitors.\n- Have received propranolol within 4 weeks prior to treatment\n- Prior to study day one received radiation therapy, chemotherapy or targeted small molecule therapy within 2 weeks and/or monoclonal antibody treatment within 4 weeks\n- Not recovered from the effects of previously administered agents\n- Clinically active or unstable CNS metastases as assessed by the treating physician"}

Primary endpoints

• {"endpoint_text":"- Percentage of patients alive with CR, PR and SD according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) at 3 months","definition_or_measurement_approach":"Assessed by RECIST v1.1 tumor response evaluation at 3 months to determine proportion of patients with complete response (CR), partial response (PR) or stable disease (SD). (Main objective also stated as PFSR at 3 months by RECIST v1.1.)"}

Secondary endpoints

• {"endpoint_text":"- Percentage of patients with CR and PR, including duration hereof using RECIST v 1.1","definition_or_measurement_approach":"Tumor responses assessed by RECIST v1.1; duration measured from first documented response to progression or death."}
• {"endpoint_text":"- Median PFS and OS","definition_or_measurement_approach":"Progression-free survival (PFS) and overall survival (OS) measured using time-to-event analysis (median values reported)."}
• {"endpoint_text":"- Adverse Events using Common Terminology Criteria for Adverse Events (CTCAE) v5.0","definition_or_measurement_approach":"Safety and tolerability assessed and graded by CTCAE v5.0."}
• {"endpoint_text":"- The 30 item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ C30) questionnaire","definition_or_measurement_approach":"Quality of life assessed using the EORTC QLQ-C30 instrument."}

Other endpoints

• {"endpoint_text":"- Exploratory: To explore the association between anti-tumor activity and specific biomarker measures in the tumor tissue and in peripheral blood","definition_or_measurement_approach":"Translational/exploratory biomarker analyses on archived or newly obtained tumor tissue and peripheral blood to assess associations with anti-tumor activity."}

Denmark

Earliest CTIS Part Ii Submission Date

16-05-2024

Latest Decision Or Authorization Date

24-05-2024

Processing Time Days

8

Number Of Sites

2

Number Of Participants

50

Norway

Earliest CTIS Part Ii Submission Date

16-05-2024

Latest Decision Or Authorization Date

23-05-2024

Processing Time Days

7

Number Of Sites

1

Number Of Participants

30

Sweden

Earliest CTIS Part Ii Submission Date

12-12-2025

Latest Decision Or Authorization Date

09-02-2026

Processing Time Days

59

Number Of Sites

1

Number Of Participants

20

Primary sponsor

Full Name

Region Hovedstaden

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Denmark

Contract research organisations

Name

CROAK AB

Responsibilities

sponsorDuties code:1

Third parties

• {"country":"Sweden","full_name":"CROAK AB","duties_or_roles":"sponsorDuties code:1","organisation_type":"Industry"}
• {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"sponsorDuties code:1","organisation_type":"Hospital/Clinic/Other health care facility"}