Immunotherapy and Carbon Ion Radiotherapy In Solid Cancers With Stable Disease (ICONIC)

May 24, 2023 updated by: CNAO National Center of Oncological Hadrontherapy

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Estimated)

27

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Chiara Campo, PhD
  • Phone Number: +39 0382078407
  • Email: campo@cnao.it

Study Contact Backup

  • Name: Cristina Bono
  • Phone Number: +39 0382078613
  • Email: bono@cnao.it

Study Locations

  • Germany
      • Darmstadt, Germany
        • Active, not recruiting
        • GSI Helmholtzzentrum für Schwerionenforschung GmbH
  • Italy
      • MIlan, Italy
        • Recruiting
        • Fondazione IRCCS Istituto Nazionale dei Tumori
        • Contact:
          • Filippo De Braud, Prof., MD
        • Principal Investigator:
          • Marco Platania, MD
      • Pavia, Italy
        • Recruiting
        • Fondazione IRCCS Policlinico San Matteo
        • Contact:
          • Paolo Pedrazzoli, Prof., MD
        • Principal Investigator:
          • Paolo Pedrazzoli, Prof., MD
      • Pavia, Italy, 27100
        • Not yet recruiting
        • National Center for Oncological Hadrontherapy (CNAO)
        • Principal Investigator:
          • Viviana Vitolo, MD
        • Sub-Investigator:
          • Ester Orlandi, MD
        • Sub-Investigator:
          • Amelia Barcellini, MD
        • Sub-Investigator:
          • Sara Ronchi, MD
        • Contact:
          • Cristina Bono
          • Phone Number: +39 0382078613
          • Email: bono@cnao.it
        • Contact:
          • Chiara Campo, PhD
          • Phone Number: +39 0382-078 407
          • Email: campo@cnao.it

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Solid cancers with stable disease

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.

Patients diagnosed with NSCLC, HNSCC, melanoma and urothelial carcinoma will be eligible for the study.
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.
Other Names:
  • Pembrolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate assessed by RECIST V1.1
Time Frame: At least 8 weeks
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.
At least 8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment-related adverse events assessed by CTCAE V5.0
Time Frame: At least 8 weeks
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.
At least 8 weeks
Efficacy in terms of survival
Time Frame: At least 8 weeks

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.
At least 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

CNAO National Center of Oncological Hadrontherapy

Collaborators

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt, Germany

Investigators

  • Principal Investigator: Viviana Vitolo, MD, Fondazione CNAO

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 26, 2022

Primary Completion (Estimated)

August 1, 2025

Study Completion (Estimated)

August 1, 2026

Study Registration Dates

First Submitted

January 10, 2022

First Submitted That Met QC Criteria

February 4, 2022

First Posted (Actual)

February 8, 2022

Study Record Updates

Last Update Posted (Actual)

May 25, 2023

Last Update Submitted That Met QC Criteria

May 24, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CNAO 44 2021 C

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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