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

Primary Purpose

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

Status

Recruiting

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Carbon Ion Therapy

Immunotherapy (Pembrolizumab)

About this trial

This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring Hadrontherapy, CIRT, Immunotherapy, NSCLC, HNSCC, Melanoma, Urothelial

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
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.
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)

Sites / Locations

GSI Helmholtzzentrum für Schwerionenforschung GmbH
Fondazione IRCCS Istituto Nazionale dei TumoriRecruiting
National Center for Oncological Hadrontherapy (CNAO)
Fondazione IRCCS Policlinico San MatteoRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Solid cancers with stable disease

Arm 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT05229614

First Posted

January 10, 2022

Last Updated

May 24, 2023

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

1. Study Identification

Unique Protocol Identification Number

NCT05229614

Brief Title

Immunotherapy and Carbon Ion Radiotherapy In Solid Cancers With Stable Disease

Acronym

ICONIC

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 26, 2022 (Actual)

Primary Completion Date

August 2025 (Anticipated)

Study Completion Date

August 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the 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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Hadrontherapy, CIRT, Immunotherapy, NSCLC, HNSCC, Melanoma, Urothelial

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

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)

Allocation

N/A

Enrollment

27 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Solid cancers with stable disease

Arm Type

Experimental

Arm Description

Intervention Type

Radiation

Intervention Name(s)

Carbon Ion Therapy

Intervention Description

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

Drug

Intervention Name(s)

Immunotherapy (Pembrolizumab)

Other Intervention Name(s)

Pembrolizumab

Intervention Description

Primary Outcome Measure Information:

Title

Objective response rate assessed by RECIST V1.1

Description

Time Frame

At least 8 weeks

Secondary Outcome Measure Information:

Title

Treatment-related adverse events assessed by CTCAE V5.0

Description

Time Frame

At least 8 weeks

Title

Efficacy in terms of survival

Description

Time Frame

At least 8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 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. 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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Chiara Campo, PhD

Phone

+39 0382078407

campo@cnao.it

First Name & Middle Initial & Last Name or Official Title & Degree

Cristina Bono

Phone

+39 0382078613

bono@cnao.it

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Viviana Vitolo, MD

Organizational Affiliation

Fondazione CNAO

Official's Role

Principal Investigator

Facility Information:

Facility Name

GSI Helmholtzzentrum für Schwerionenforschung GmbH

City

Darmstadt

Country

Germany

Individual Site Status

Active, not recruiting

Facility Name

Fondazione IRCCS Istituto Nazionale dei Tumori

City

MIlan

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Filippo De Braud, Prof., MD

First Name & Middle Initial & Last Name & Degree

Marco Platania, MD

Facility Name

National Center for Oncological Hadrontherapy (CNAO)

City

Pavia

ZIP/Postal Code

27100

Country

Italy

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Chiara Campo, PhD

Phone

+39 0382-078 407

campo@cnao.it

First Name & Middle Initial & Last Name & Degree

Cristina Bono

Phone

+39 0382078613

bono@cnao.it

First Name & Middle Initial & Last Name & Degree

Viviana Vitolo, MD

First Name & Middle Initial & Last Name & Degree

Ester Orlandi, MD

First Name & Middle Initial & Last Name & Degree

Amelia Barcellini, MD

First Name & Middle Initial & Last Name & Degree

Sara Ronchi, MD

Facility Name

Fondazione IRCCS Policlinico San Matteo

City

Pavia

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Paolo Pedrazzoli, Prof., MD

First Name & Middle Initial & Last Name & Degree

Paolo Pedrazzoli, Prof., MD

12. IPD Sharing Statement

Plan to Share IPD

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Immunotherapy and Carbon Ion Radiotherapy In Solid Cancers With Stable Disease

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