Immunotherapy and Carbon Ion Radiotherapy In Solid Cancers With Stable Disease

NCT ID: NCT05229614

Last Updated: 2024-08-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-26

Study Completion Date

2026-08-31

Brief Summary

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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

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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

Conditions

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Non Small Cell Lung Cancer Head and Neck Squamous Cell Carcinoma Melanoma Urothelial Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Patient with solid cancer (NSCLC, HNSCC, melanoma, urothelial carcinoma) and a stable disease will be enrolled in the study.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Carbon Ion Therapy

Intervention Type RADIATION

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)

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type RADIATION

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.

Intervention Type DRUG

Other Intervention Names

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Pembrolizumab

Eligibility Criteria

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Inclusion Criteria

1. Signed written informed consent
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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

UNKNOWN

Sponsor Role collaborator

Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

UNKNOWN

Sponsor Role collaborator

GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt, Germany

UNKNOWN

Sponsor Role collaborator

CNAO National Center of Oncological Hadrontherapy

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Viviana Vitolo, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione CNAO

Locations

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GSI Helmholtzzentrum für Schwerionenforschung GmbH

Darmstadt, , Germany

Site Status ACTIVE_NOT_RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status RECRUITING

National Center for Oncological Hadrontherapy (CNAO)

Pavia, , Italy

Site Status NOT_YET_RECRUITING

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Site Status RECRUITING

Countries

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Germany Italy

Central Contacts

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Chiara Campo, PhD

Role: CONTACT

+39 0382078407

Cristina Bono

Role: CONTACT

+39 0382078613

Facility Contacts

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Filippo De Braud, Prof., MD

Role: primary

Chiara Campo, PhD

Role: primary

+39 0382-078 407

Cristina Bono

Role: backup

+39 0382078613

Paolo Pedrazzoli, Prof., MD

Role: primary

References

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Other Identifiers

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CNAO 44 2021 C

Identifier Type: -

Identifier Source: org_study_id

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