About this trial
Immunotherapy has become the standard of care in different advanced malignancies. Its effectiveness in the palliative setting was demonstrated by several phase III trials. However, the response rate varies according to the cancer under study and to the line of treatment. A potential way to improve the activity of single agent immune checkpoint inhibitors (ICIs) is to enhance the clinical response through further antitumor agents, including radiotherapy. Studies showed that carbon ions may lead to a broader immunogenic response; for their dosimetric characteristics it is possible to reduce integral dose sparing immune cells to direct and sustain a tumor specific immune response.
Considering the available preclinical and clinical evidence together, the goal of this study is to explore the feasibility and the clinical activity of adding carbon ion radiotherapy (CIRT), employed with a fractionation strategy comparable to stereotactic body radiation, to ICIs in advanced malignancies where immunotherapy is currently the standard of care.
Eligibility criteria
Qualifiers
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
Disqualifiers
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
Trial design
Treatments tested in this trial
- Carbon Ion Therapy
- Immunotherapy (Pembrolizumab)
Treatment groups
Sponsors and collaborators
CNAO National Center of Oncological Hadrontherapy
Lead sponsor
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
Collaborator
Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Collaborator
GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt, Germany
Collaborator