• Unresectable or metastatic melanoma • Locally advanced or metastatic non-small cell lung cancer (NSCLC) • Untreated recurrent/metastatic head & neck sqamous cell carcinoma (HNSCC) • Locally advanced or metastatic urothelial carcinoma MedDRA version: 20.0 Level: HLT Classification code 10027467 Term: Metastases to specified sites System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: SOC Classification
Conditions
Interventions
Product Name: Pembrolizumab
Product Code: [044386]
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
Current Sponsor code: AIC 044386
Concentrati
Sponsors
Fondazione CNAO Centro Nazionale di Adroterapia Oncologica
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed written informed consent 2) 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) 3) Having a disease stability as assessed by AIFA monitoring sheet 4) 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 5) Willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study 6) Females and males, 18 years of age or older (no upper limit for age) 7) Eastern Cooperative Oncology Group (ECOG) performance status = 2 8) Subjects must have measurable disease by CT or MRI per RECIST 1.1 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: 1) Patients treated with chemo-immunotherapy associations 2) Patients treated with immunotherapy combinations (e.g. subjects treated with anti-CTLA4 + anti-PD1/PDL1 are excluded) 3) Patients receiving immunotherapy within clinical trials 4) Patients receiving off-label immunotherapy or within expanded access programs or as compassionate use 5) Patients with high tumor burden defined as > 10 lesions and/or sum of diameters > 19 cm 6) Patients with distant metastases only located in the CNS are excluded 7) 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 8) Patients with autoimmune diseases (ADs), including local and systemic collagen-vascular (CVD) and inflammatory bowel diseases (IBD). Controlled 9) Previous RT, regardless of energy, on the metastatic site selected to be irradiated. 10) Any immune-related CTCAE grade 4 adverse event, before study entry. 11) Any CTCAE grade=3 immune-related adverse event observed within 3 weeks prior to CIRT start 12) Presence of metal prostheses or any other condition to prevent adequate imaging for identification of the target volume and calculation of the dose 13) Loco-regional conditions not allowing hadron therapy (e.g. active infections in RT target region) 14) Prisoners or subjects who are involuntarily incarcerated 15) Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness (e.g. infectious disease)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the effect, in terms of clinical response, of immunotherapy associating carbon ion treatment in the palliative setting across different malignancies, for which immunotherapy is currently the standard of care.;Secondary Objective: 1.To describe the safety profile of the association of carbon ion radiation therapy and systemic immunotherapy in the palliative setting across different malignancies, for which immunotherapy is currently the standard of care 2.To estimate the effect, in terms of survival, of immunotherapy with the association of carbon ion radiation treatment in the palliative setting across different malignancies, for which immunotherapy is currently the standard of care.;Primary end point(s): objective response rate (ORR) according to RECIST, assessed at least 8 weeks after CIRT;Timepoint(s) of evaluation of this end point: at least 8 weeks after CIRT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): progression-free survival (PFS); overall survival (OS); Tasso di risposta obiettiva (ORR) secondo i criteri irRECIST; percentage of patients with disease progression as best response; objective response of the metastatic lesion treated with CIRT; disease control rate (DCR) according to RECIST, defined as ORR+SD; toxicity according to CTCAE version 5.0;Timepoint(s) of evaluation of this end point: at least 8 weeks after CIRT; at least 8 weeks after CIRT; at least 8 weeks after CIRT; at least 8 weeks after CIRT; at least 8 weeks after CIRT; at least 8 weeks after CIRT; at least 8 weeks after CIRT | — |
Countries
Italy
Contacts
Public ContactDirezione Scientifica
CNAO
Outcome results
None listed