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RECRUITING

NCT05229614

PHASE2

Immunotherapy and Carbon Ion Radiotherapy In Solid Cancers With Stable Disease

Sponsor: CNAO National Center of Oncological Hadrontherapy

View on ClinicalTrials.gov

Summary

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.

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

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2022-07-26

Completion Date

2026-08

Last Updated

2024-08-21

Healthy Volunteers

Conditions

Non Small Cell Lung Cancer Head and Neck Squamous Cell Carcinoma Melanoma Urothelial Carcinoma

Interventions

RADIATION

Carbon Ion Therapy

After confirming the disease stability and upon patient inclusion in the study, hypofractionated carbon ion boost will be administered to one site of disease previously untreated. Patient will be irradiated to a single lesion with a total dose of 24 Gy\[RBE\], 8 Gy\[RBE\]/fraction, one fraction/day, for 3 days.

DRUG

Immunotherapy (Pembrolizumab)

Only cancer patients under treatment with pembrolizumab monotherapy, administered within clinical practice and according to the Italian Drug Regulatory Agency (Agenzia Italiana del Farmaco, AIFA), will be enrolled.

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)

Locations (4)

GSI Helmholtzzentrum für Schwerionenforschung GmbH

Darmstadt, Germany

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

National Center for Oncological Hadrontherapy (CNAO)

Pavia, Italy

Fondazione IRCCS Policlinico San Matteo