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Non Small Cell Lung CancerPhase 2ICONICNCT05229614

Immunotherapy and Carbon Ion Radiotherapy In Solid Cancers With Stable Disease

A Phase 2 study testing Carbon Ion Therapy and Immunotherapy (Pembrolizumab) in people with Non Small Cell Lung Cancer and Head and Neck Squamous Cell Carcinoma, run by CNAO National Center of Oncological Hadrontherapy at 4 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Carbon Ion Therapy and Immunotherapy (Pembrolizumab)
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
4 sitesin 2 countries
Study dates
26 Jul 2022to Aug 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
  • 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
Show all 15Show fewer
  • 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.
  • 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)

Trial locations and contacts

4 sites in 2 countries.

Chiara Campo, PhD contact

+39 0382078407

campo@cnao.it

Cristina Bono contact

+39 0382078613

bono@cnao.it

4 sites in 2 countries

Italy3 sites, 3 recruiting

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan

    Filippo De Braud, Prof., MD

    Marco Platania, MD

    Recruiting

  • National Center for Oncological Hadrontherapy (CNAO)

    Pavia, 27100

    Chiara Campo, PhD, +39 0382-078 407, campo@cnao.it

    Cristina Bono, +39 0382078613, bono@cnao.it

    Not yet recruiting

  • Fondazione IRCCS Policlinico San Matteo

    Pavia

    Paolo Pedrazzoli, Prof., MD

    Paolo Pedrazzoli, Prof., MD

    Recruiting

Other trials in Italy

Germany1 site

  • GSI Helmholtzzentrum für Schwerionenforschung GmbH

    Darmstadt

    Active, not recruiting

Other trials in Germany

About this study

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

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.

Read the 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

Being tested
Carbon Ion Therapy, Immunotherapy (Pembrolizumab)
Keywords
Hadrontherapy, CIRT, Immunotherapy, NSCLC, HNSCC, Melanoma, Urothelial
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of Head and Neck, Melanoma, Carcinoma, Transitional Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Carbon Ion TherapyRadiation

    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.

  • Immunotherapy (Pembrolizumab)Drug

    Also called 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.

Study groups in NCT05229614
Study groupRoleWhat they receive
Solid cancers with stable diseaseExperimentalOnly 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. Patients diagnosed with NSCLC, HNSCC, melanoma and urothelial carcinoma will be eligible for the study.
Receives: Radiation: Carbon Ion Therapy; Drug: Immunotherapy (Pembrolizumab)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate assessed by RECIST V1.1

    To estimate the effect, in terms of clinical response, of immunotherapy associating carbon ion treatment (CIRT) in the palliative setting across different malignancies, for which immunotherapy is currently the standard of care. Objective response rate (ORR) will be evaluated after CIRT administrated during immunotherapy maintenance in patients with stable disease. ORR will be assessed in the whole population according to RECIST v1.1. The proportion of ORR will be estimated within each disease.

    Measured: At least 8 weeks

Secondary outcomes (2)

  1. Treatment-related adverse events assessed by CTCAE V5.0

    To describe the safety profile of the association of carbon ion radiation therapy and systemic immunotherapy in the palliative setting across different malignancies, for which immunotherapy is currently the standard of care. Treatment-related adverse events will be evaluated according to CTCAE version 5.0.

    Measured: At least 8 weeks

  2. Efficacy in terms of survival

    To estimate the effect, in terms of survival, of immunotherapy with the association of carbon ion radiation treatment in the palliative setting across different malignancies, for which immunotherapy is currently the standard of care.

    Progression-Free Survival (PFS) will be calculated as the time between the start date of immunotherapy associated with carbon ion and the progression of disease, or death or last-follow-up. PFS will be estimated, within each malignancy, by Kaplan-Meier product limit method.

    Overall survival (OS) will be calculated as the time between the start date of immunotherapy associated with carbon ion and the death for any cause or last follow-up. OS will be estimated, within each malignancy, by Kaplan-Meier product limit method.

    Measured: At least 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2022
  2. Study start26 Jul 2022
  3. Primary completionAug 2025 (estimated)
  4. Study completionAug 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Patient with solid cancer (NSCLC, HNSCC, melanoma, urothelial carcinoma) and a stable disease will be enrolled in the study.
Masking
None (open label)
Enrolment
27 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05229614
Sponsor's protocol ID
CNAO 44 2021 C
Acronym
ICONIC
Status last verified
Aug 2024
First submitted
10 Jan 2022
Last updated
21 Aug 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeno J, Faivre-Finn C, Reck M, Vansteenkiste J, Spigel DR, Wadsworth C, Melillo G, Taboada M, Dennis PA, Ozguroglu M; PACIFIC Investigators. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med. 2018 Dec 13;379(24):2342-2350. doi: 10.1056/NEJMoa1809697. Epub 2018 Sep 25.

    PubMed 30280658

  • Dewan MZ, Galloway AE, Kawashima N, Dewyngaert JK, Babb JS, Formenti SC, Demaria S. Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res. 2009 Sep 1;15(17):5379-88. doi: 10.1158/1078-0432.CCR-09-0265. Epub 2009 Aug 25.

    PubMed 19706802

  • Durante M, Paganetti H. Nuclear physics in particle therapy: a review. Rep Prog Phys. 2016 Sep;79(9):096702. doi: 10.1088/0034-4885/79/9/096702. Epub 2016 Aug 19.

    PubMed 27540827

  • Deng L, Liang H, Xu M, Yang X, Burnette B, Arina A, Li XD, Mauceri H, Beckett M, Darga T, Huang X, Gajewski TF, Chen ZJ, Fu YX, Weichselbaum RR. STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors. Immunity. 2014 Nov 20;41(5):843-52. doi: 10.1016/j.immuni.2014.10.019. Epub 2014 Nov 6.

    PubMed 25517616

  • Vanpouille-Box C, Alard A, Aryankalayil MJ, Sarfraz Y, Diamond JM, Schneider RJ, Inghirami G, Coleman CN, Formenti SC, Demaria S. DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nat Commun. 2017 Jun 9;8:15618. doi: 10.1038/ncomms15618.

    PubMed 28598415

  • Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum RR, Fu YX. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 2014 Feb;124(2):687-95. doi: 10.1172/JCI67313. Epub 2014 Jan 2.

    PubMed 24382348

  • Antonioli L, Blandizzi C, Pacher P, Hasko G. Immunity, inflammation and cancer: a leading role for adenosine. Nat Rev Cancer. 2013 Dec;13(12):842-57. doi: 10.1038/nrc3613. Epub 2013 Nov 14.

    PubMed 24226193

  • Golden EB, Demaria S, Schiff PB, Chachoua A, Formenti SC. An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer. Cancer Immunol Res. 2013 Dec;1(6):365-72. doi: 10.1158/2326-6066.CIR-13-0115.

    PubMed 24563870

  • Dovedi SJ, Adlard AL, Lipowska-Bhalla G, McKenna C, Jones S, Cheadle EJ, Stratford IJ, Poon E, Morrow M, Stewart R, Jones H, Wilkinson RW, Honeychurch J, Illidge TM. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 2014 Oct 1;74(19):5458-68. doi: 10.1158/0008-5472.CAN-14-1258.

    PubMed 25274032

  • Tang C, Welsh JW, de Groot P, Massarelli E, Chang JY, Hess KR, Basu S, Curran MA, Cabanillas ME, Subbiah V, Fu S, Tsimberidou AM, Karp D, Gomez DR, Diab A, Komaki R, Heymach JV, Sharma P, Naing A, Hong DS. Ipilimumab with Stereotactic Ablative Radiation Therapy: Phase I Results and Immunologic Correlates from Peripheral T Cells. Clin Cancer Res. 2017 Mar 15;23(6):1388-1396. doi: 10.1158/1078-0432.CCR-16-1432. Epub 2016 Sep 20.

    PubMed 27649551

  • Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

    PubMed 19097774

  • Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbe C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009 Dec 1;15(23):7412-20. doi: 10.1158/1078-0432.CCR-09-1624. Epub 2009 Nov 24.

    PubMed 19934295

  • Cavalieri S, Vitolo V, Barcellini A, Ronchi S, Facoetti A, Campo C, Klersy C, Molinelli S, Agustoni F, Ferretti VV, Silvestri A, Platania M, Del Vecchio M, Durante M, Helm A, Fournier C, Braud F, Pedrazzoli P, Orlandi E, Licitra L. Immune checkpoint inhibitors and Carbon iON radiotherapy In solid Cancers with stable disease (ICONIC). Future Oncol. 2023 Jan;19(3):193-203. doi: 10.2217/fon-2022-0503. Epub 2023 Mar 28.

    PubMed 36974574

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carbon Ion Therapy and Immunotherapy (Pembrolizumab) in people with Non Small Cell Lung Cancer and Head and Neck Squamous Cell Carcinoma, run by CNAO National Center of Oncological Hadrontherapy at 4 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 21 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Italy, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Chiara Campo, PhD (+39 0382078407, campo@cnao.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate assessed by RECIST V1.1 (time frame: At least 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05229614, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2024.

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