pembrolizumab for Metastatic melanoma | Urothelial carcinoma | Non-small cell lung cancer | Head and neck squamous cell carcinoma

Inclusion criteria

• {"criterion_text":"- Signed written informed consent\n- Histologic confirmation of malignancies under treatment with single agent anti-PD1/PDL1 immunotherapy per clinical practice (see cohort specific inclusion criteria) with immune checkpoint inhibitors approved by Italian national drug regulatory agencies (Agenzia Italiana del Farmaco, AIFA)\n- Having a disease stability as assessed by AIFA monitoring sheet\n- Presence of at least 2 measurable target lesions, of which at least one to be followed up as per RECIST and one suitable for CIRT\n- Willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study\n- Females and males, 18 years of age or older (no upper limit for age)\n- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2\n- Subjects must have measurable disease by CT or MRI per RECIST 1.1"}

Exclusion criteria

• {"criterion_text":"- Patients treated with chemo-immunotherapy associations\n- Any immune-related CTCAE grade 4 adverse event, before study entry\n- Any CTCAE grade ≥3 immune-related adverse event observed within 3 weeks prior to CIRT start\n- Presence of metal prostheses or any other condition to prevent adequate imaging for identification of the target volume and calculation of the dose\n- Loco-regional conditions not allowing hadron therapy (e.g. active infections in RT target region)\n- Prisoners or subjects who are involuntarily incarcerated\n- Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness (e.g. infectious disease)\n- Patients treated with immunotherapy combinations (e.g. subjects treated with anti-CTLA4 + anti-PD1/PDL1 are excluded)\n- Patients receiving immunotherapy within clinical trials\n- Patients receiving off-label immunotherapy or within expanded access programs or as compassionate use\n- Patients with high tumor burden defined as > 10 lesions and/or sum of diameters > 19 cm\n- Patients with distant metastases only located in the CNS are excluded\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- Patients with autoimmune diseases (ADs), including local and systemic collagen-vascular (CVD) and inflammatory bowel diseases (IBD)\n- Previous RT, regardless of energy, on the metastatic site selected to be irradiated"}

Primary endpoints

• {"endpoint_text":"- Objective response rate (ORR) according to RECIST, assessed at least 8 weeks after CIRT","definition_or_measurement_approach":"ORR measured according to RECIST; assessment performed at least 8 weeks after carbon ion radiotherapy (CIRT)."}
• {"endpoint_text":"- Toxicity according to CTCAE version 5.0","definition_or_measurement_approach":"Toxicity graded and recorded according to CTCAE v5.0."}

Secondary endpoints

• {"endpoint_text":"- progression-free survival (PFS)","definition_or_measurement_approach":"PFS measured as time from enrollment to documented disease progression or death (standard PFS definition; method not further specified in provided data)."}
• {"endpoint_text":"- overall survival (OS)","definition_or_measurement_approach":"OS measured as time from enrollment to death from any cause."}
• {"endpoint_text":"- objective response rate (ORR) according to irRECIST","definition_or_measurement_approach":"ORR assessed using immune-related RECIST (irRECIST)."}
• {"endpoint_text":"- percentage of patients with disease progression as best response","definition_or_measurement_approach":"Proportion of patients whose best overall response is disease progression (method not further specified)."}
• {"endpoint_text":"- objective response of the metastatic lesion treated with CIRT","definition_or_measurement_approach":"Objective response of the irradiated metastatic lesion assessed (specific response criteria not further detailed)."}
• {"endpoint_text":"- disease control rate (DCR) according to RECIST, defined as ORR+SD","definition_or_measurement_approach":"DCR defined as ORR plus stable disease, measured per RECIST."}

Italy

Earliest CTIS Part Ii Submission Date

27-09-2024

Latest Decision Or Authorization Date

26-11-2024

Processing Time Days

60

Number Of Sites

3

Number Of Participants

27

Primary sponsor

Full Name

Fondazione Centro Nazionale Di Adroterapia Oncologica

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy