Immunotherapy and Carbon Ion Radiotherapy In Solid Cancers With Stable Disease

This is a multicenter, open label, non-randomized phase II clinical trial aiming to assess the feasibility and the clinical activity of adding CIRT to ICIs in cancer patients that have obtained a disease stability (SD) with pembrolizumab administered as per standard of care. At study entry, hypofractionated CIRT will be delivered to one measurable lesion previously untreated with local approaches.CIRT will be performed at Fondazione CNAO, Pavia

Inclusion criteria

• Signed written informed consent
• 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)
• Having a disease stability as assessed by AIFA monitoring sheet
• 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
• Willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
• Females and males, 18 years of age or older (no upper limit for age)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Subjects must have measurable disease by CT or MRI per RECIST 1.1

Exclusion criteria

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