Immunotherapy and Carbon Ion Radiotherapy In Solid Cancers With Stable Disease

Brief Title

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

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
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Objective response rate assessed by RECIST V1.1

Secondary Outcome

 Treatment-related adverse events assessed by CTCAE V5.0

Condition

Non Small Cell Lung Cancer

Intervention

Carbon Ion Therapy

Study Arms / Comparison Groups

 Solid cancers with stable disease

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Radiation

Estimated Enrollment

27

Start Date

July 26, 2022

Completion Date

August 2026

Primary Completion Date

August 2025

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)
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Viviana Vitolo, MD, +39 0382078407, [email protected]

Location Countries

Germany

Location Countries

Germany

NCT ID

NCT05229614

Organization ID

CNAO 44 2021 C

Responsible Party

Sponsor

Study Sponsor

CNAO National Center of Oncological Hadrontherapy

Collaborators

 Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

Study Sponsor

Viviana Vitolo, MD, Principal Investigator, Fondazione CNAO

Verification Date

February 2022