Secondary angiosarcomas soft tissue sarcoma
Conditions
Interventions
In this study we want to evaluate the effect cemiplimab, a known drug
registered for another type of cancer, in patients with locally advanced or
metastatic secondary angiosarcomas. Patients in the
Sponsors
Radboud Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Adult patient aged >= 18 years. 2. Signed written informed consent. 3. Histologically confirmed diagnosis of progressive unresectable locally advanced or metastatic secondary angiosarcoma. 4. Patients in the first line of systemic treatment unfit for chemotherapy and patients in advanced lines of systemic treatment 5. Measurable disease per RECIST 1.1 or per physical examination / daylight photography (WHO Offset Publication No. 48) as determined by the investigator. 6. Tumour tissue material available (archival or recent tumour biopsy). 7. WHO ECOG 0-2. 8. Hepatic function: a. Total bilirubin 30 mL/min. 10. Creatine phosphokinase (CPK) (also known as CK [creatine kinase]) elevation = 9.0 g/dL. b. ANC >= 1.5 x 109/L. c. Platelet count >= 75 x 109/L. 12. Expected life expectancy of at least 3 months as judged by the investigator.
Exclusion criteria
Exclusion criteria: 1. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for irAEs. The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 Diabetes mellitus, residual hypothyroidism that required only hormone therapy, or psoriasis that does not require systematic treatment. 2. Prior treatment with immune checkpoint inhibitors. 3. Continuous immunosuppressive corticosteroid treatment (doses > 10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab. Note: patients who require a brief course of steroids (e.g. as prophylaxis for imaging studies) are not excluded. 4. Active uncontrolled infection requiring therapy, including infection with HIV, active infection with HBV or HCV. 5. History of pneumonitis within the last 5 years. 6. Untreated brain metastasis(es) that may be considered active. a. Note in clarification: Patients with previously treated brain metastases may participate provided that the lesion(s) is (are) stable (without evidence of progression for at least 6 weeks on imaging obtained in the screening period), and there is no evidence of new or enlarging brain metastases, and the patients do not require any immunosuppressive doses of systemic corticosteroids for management of brain metastasis(es) within 28 days of the first dose of cemiplimab. 7. Patients with allergy or hypersensitivity to cemiplimab or to any of the excipients must be excluded. Specifically, because of the presence of trace components in cemiplimab, patients with allergy or hypersensitivity to doxycycline or tetracycline are excluded. 8. History of documented allergic reactions or acute hypersensitivity reaction attributed to antibody treatments 9. Patients with a history of solid organ transplant (patients with prior corneal transplants may be allowed to enroll after discussion with and approval from the medical monitor). 10. Any anticancer treatment other than radiation therapy (chemotherapy, targeted systemic therapy, imiquimod, photodynamic therapy), investigational or standard of care, within 30 days of the initial administration of cemiplimab or planned to occur during the study period 11. Receipt of live vaccines (including attenuated) within 30 days of first study treatment 12. Prior use of PI3K-D inhibitors 13. Women of childbearing potential (WOCBP)*, or sexually active men, who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment prior to the start of the first treatment, during the study, and for at least 6 months after the last dose. 14. Breastfeeding 15. Positive serum pregnancy test (a false positive pregnancy test, if demonstrated by serial measurements and negative ultrasound, will not be exclusionary, upon communication with and approval from the medical monitor) 16. Any other condition that might interfere with experimental treatment and the study procedures as judged by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary objective: 1) To evaluate the overall response rate (ORR) after 24 weeks of cemiplimab in secondary angiosarcomas, according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 or daylight photography as per WHO Offset Publication No. 48. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objectives: 1) To establish the best ORR of patients with secondary angiosarcomas receiving cemiplimab. 2) To establish the median time to response (TTR) and duration of response (DOR) in patients with secondary angiosarcomas receiving cemiplimab. 3) To assess the median progression-free survival (PFS) of patients with secondary angiosarcomas receiving cemiplimab. 4) To establish the overall survival (OS) of patients with secondary angiosarcomas receiving cemiplimab. 5) To investigate possible relations between response to cemiplimab and tumour characteristics (i.e. PD-L1 expression, tumour infiltrating lymphocytes, MYC status and tumour mutational burden). 6) To assess differences in response to cemiplimab between UV associated and radiation induced secondary angiosarcomas. 7) To assess effects of cemiplimab on tumour tissue by comparing pre- and post-treatment biopsies. 8) To quantify toxicity during cemiplimab treatment. | — |
Countries
Netherlands
Outcome results
None listed