Immune checkpoint inhibitors and Carbon iON radiotherapy In solid Cancers with stable disease (ICONIC)

Phase 2

Not yet recruiting

Conditions: Unresectable or metastatic melanoma
Locally advanced or metastatic urothelial carcinoma
Locally advanced or metastatic non-small cell lung cancer (NSCLC)
Untreated recurrent/metastatic head & neck sqamous cell carcinoma (HNSCC)

Registration Number: 2024-517378-22-00

Lead Sponsor: Fondazione Centro Nazionale Di Adroterapia Oncologica

Brief Summary: To estimate the effect, in terms of clinical response, of immunotherapy associating carbon ion treatment in the palliative setting across different malignancies, for which 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

Recruitment & Eligibility

Status: Authorised, recruitment pending

Sex: Not specified

Target Recruitment: 27

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

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)

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Objective response rate (ORR) according to RECIST, assessed at least 8 weeks after CIRT		Objective response rate (ORR) according to RECIST, assessed at least 8 weeks after CIRT
Toxicity according to CTCAE version 5.0		Toxicity according to CTCAE version 5.0

Secondary Outcome Measures

Name	Time	Method
overall survival (OS)		overall survival (OS)
objective response rate (ORR) according to irRECIST		objective response rate (ORR) according to irRECIST
objective response of the metastatic lesion treated with CIRT		objective response of the metastatic lesion treated with CIRT
disease control rate (DCR) according to RECIST, defined as ORR+SD		disease control rate (DCR) according to RECIST, defined as ORR+SD
progression-free survival (PFS)		progression-free survival (PFS)
percentage of patients with disease progression as best response		percentage of patients with disease progression as best response

Trial Locations

Locations (3): Fondazione Centro Nazionale Di Adroterapia Oncologica
🇮🇹
Pavia, Italy
Istituto Nazionale Dei Tumori
🇮🇹
Milan, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹
Pavia, Italy
Fondazione Centro Nazionale Di Adroterapia Oncologica
🇮🇹Pavia, Italy
Viviana Vitolo
Site contact
+3903820781
vivia.vitolo@cnao.it