Clinical trial NCT05229614: Immunotherapy and Carbon Ion Radiotherapy In Solid Cancers With Stable Disease
Official title: Immune Checkpoint Inhibitors and Carbon iON Radiotherapy In Solid Cancers With Stable Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Head and Neck Squamous Cell Carcinoma
Melanoma
Urothelial Carcinoma
Keywords: Hadrontherapy
CIRT
Immunotherapy
NSCLC
HNSCC
Melanoma
Urothelial
Lead sponsor: CNAO National Center of Oncological Hadrontherapy
Sponsor class: OTHER
Collaborators: name: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
name: Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
name: GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt, Germany
First posted: 2022-02-08
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patient with solid cancer (NSCLC, HNSCC, melanoma, urothelial carcinoma) and a stable disease will be enrolled in the study.
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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

Eligibility 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)

Primary outcomes:
measure: Objective response rate assessed by RECIST V1.1
timeFrame: At least 8 weeks
Secondary outcomes:
measure: Treatment-related adverse events assessed by CTCAE V5.0
timeFrame: At least 8 weeks
measure: Efficacy in terms of survival
timeFrame: At least 8 weeks
Other outcomes:
Locations:
city: Darmstadt
country: Germany
facility: GSI Helmholtzzentrum für Schwerionenforschung GmbH
city: MIlan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Pavia
country: Italy
facility: National Center for Oncological Hadrontherapy (CNAO)
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
Study officials:
affiliation: Fondazione CNAO
name: Viviana Vitolo, MD
role: PRINCIPAL_INVESTIGATOR
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