Combining immunotherapy with carbon ion radiotherapy for solid cancers with stable disease

Immune Checkpoint Inhibitors and Carbon iON Radiotherapy In Solid Cancers With Stable Disease

Phase 2 Interventional CNAO National Center of Oncological Hadrontherapy · NCT05229614

This study is testing if adding a special type of radiation therapy to an immune treatment can help people with advanced solid cancers that are stable feel better and fight their tumors more effectively.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment27 (estimated)
Ages18 Years and up
SexAll
SponsorCNAO National Center of Oncological Hadrontherapy Academic / other
Drugs / interventionsimmunotherapy, radiation, pembrolizumab
Locations4 sites (Darmstadt and 3 other locations)
Trial IDNCT05229614 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the feasibility and clinical activity of adding carbon ion radiotherapy (CIRT) to immune checkpoint inhibitors (ICIs) in patients with advanced solid cancers who have achieved stable disease. Participants will receive hypofractionated CIRT targeting one measurable lesion that has not been previously treated locally, alongside standard treatment with pembrolizumab. The study aims to enhance the immune response against tumors by leveraging the unique properties of carbon ion therapy. It is a multicenter, open-label, non-randomized phase II trial conducted at multiple locations in Italy and Germany.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with stable disease in specific advanced malignancies who are receiving pembrolizumab as part of their treatment.

Not a fit: Patients who have previously received chemo-immunotherapy combinations or those with unstable disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with advanced solid tumors by enhancing the effectiveness of immunotherapy.

How similar studies have performed: While the combination of immunotherapy and radiotherapy has been explored, the specific use of carbon ion therapy in this context is relatively novel and has not been extensively tested in prior studies.

Eligibility criteria

Show full inclusion / exclusion 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

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)
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)

Where this trial is running

Darmstadt and 3 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Non Small Cell Lung CancerHead and Neck Squamous Cell CarcinomaMelanomaUrothelial CarcinomaHadrontherapyCIRTImmunotherapyNSCLC
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.