Immune PET and Proteomics for the Assessment of Response to Spatially Fractionated or Palliative Radiotherapy With or Without Immunotherapy

NCT06976021 | Not Yet Recruiting Phase 2

• 1 other identifier: 23/ABM/01/00078
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of the study is to evaluate the response to four schemes of treatment with novel diagnostic tools - Immuno-PET and proteomics as well as standard imaging (magnetic resonsonce imaging and computed tomography). Two fractionation schedules of radiotherapy will be used. The first will be a common standard of palliative irradiation - 20 Gy delivered in five fractions of 4 Gy (SHORT). The other is called Spatially Fractionated Radiotherapy (SFRT). SFRT is delivered in one fraction of 20 Gy but the dose is diversified inside the tumor to produce areas of high and low doses distributed alternately. This kind of irradiation may be able to stimulate immune response and improve the efficiency of immunotherapy. A drug belonging to the class of immunotherapeutic agents - Pembrolizumab will be added to the treatment scheme in two arms of the study to check that assumption. The response of the target tumor will be evaluated with PET study using Pembrolizumab labeled with zirconium-89 which will show the spatial distribution of immune receptors within the target tumor and other involved sites if there are any. The examination will be repeated after the treatment to evaluate changes in distribution of the immune receptors necessary for the drug to work. Additionally, the researchers will repeatedly test the presence and concentration of a wide panel of proteins in blood to evaluate response to the treatment more precisely.

Conditions

Triple Negative Breast Cancer; Uterine Cervical Cancer; Uterine Corpus Cancer; Malignant Melanoma; Clear Cell Renal Cell Carcinoma

Keywords

spatially fractionated radiotherapy; immunotherapy; immuno-PET; proteomics; signaling pathways

Outcome Measures

Primary Outcomes (3)

• Change in expression of PD-1 receptors expressed as a ratio of SUV values

  The expression of PD-1 receptors will be measured with Immuno-PET basing on Zr-89 labeled Pembrolizumab and expressed as the ratio of initial and post-treatment SUV

  one year

• Change in number of areas with PD-1 receptors expressed as number of lesions

  The localization of regions expressing PD-1 receptors will be identified with Immuno-PET basing on Zr-89 labeled Pembrolizumab and expressed as the number of lesions

  one year

• Change of proteome expression profile after treatment expressed in NPX (Normalized Protein eXpression) values

  The difference between proteome expression profile before treatment and after the last infusion of Pembrolizumab or after a year in arms without immunotherapy. The Proximity Extension Assay (PEA) technology will be used. Following sequencing, the raw data will be converted to counts, assigning an integer value to each assay-sample combination based on the detected copy numbers. These raw data counts will be converted into NPX values, enabling the identification of protein level changes within different sample sets, and establishing protein signatures.

  one year

Study Arms (4)

SFRT with immunotherapy

EXPERIMENTAL

Diagnostic Test: Baseline 89-Zr Pembrolizumab Immuno PET-CT; Diagnostic Test: Proteomic assay

SHORT with immunotherapy

ACTIVE COMPARATOR

Diagnostic Test: Baseline 89-Zr Pembrolizumab Immuno PET-CT; Diagnostic Test: Proteomic assay

SFRT

EXPERIMENTAL

Diagnostic Test: Baseline 89-Zr Pembrolizumab Immuno PET-CT; Diagnostic Test: Proteomic assay; Diagnostic Test: Follow-up 89-Zr Pembrolizumab Immuno PET-CT

SHORT

ACTIVE COMPARATOR

Diagnostic Test: Baseline 89-Zr Pembrolizumab Immuno PET-CT; Diagnostic Test: Proteomic assay; Diagnostic Test: Follow-up 89-Zr Pembrolizumab Immuno PET-CT

Interventions

Baseline 89-Zr Pembrolizumab Immuno PET-CT DIAGNOSTIC_TEST

Diagnostic imaging with novel radiotracer - drug (Pembrolizumab) labeled with zirconium-89

SFRT; SFRT with immunotherapy; SHORT; SHORT with immunotherapy

Proteomic assay DIAGNOSTIC_TEST

Assessment of the proteomic profile before and periodically after treatment

SFRT; SFRT with immunotherapy; SHORT; SHORT with immunotherapy

Follow-up 89-Zr Pembrolizumab Immuno PET-CT DIAGNOSTIC_TEST

Diagnostic imaging with novel radiotracer - drug (Pembrolizumab) labeled with zirconium-89 after radiotherapy performed in patients who are not treated with immunotherapy

SFRT; SHORT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed diagnosis of clear cell renal cell carcinoma, melanoma, cervical cancer, endometrial cancer or triple negative breast cancer.
• Patients nnot eligible for radical treatment with radiotherapy (including stereotactic radiotherapy of the tumor in the potential planned area of irradiation in the study), chemotherapy and palliative immunotherapy in accordance with applicable national standards but who qualify for palliative radiation treatment
• General condition according to Karnofsky scale: 60-100
• The tumor may be assessed using iRECIST
• Age over 18 years
• Granted written, informed consent to participate in the research experiment
• No contraindications to treatment with Pembrolizumab (according to the information provided in the product characteristics).
• Expected survival time over 6 months.

You may not qualify if:

• Lack of consent to participate in the experiment
• Contraindications to Pembrolizumab according to the product characteristics
• Pregnancy and lactation
• Inability of the patient to cooperate, including claustrophobia that prevents imaging tests from being performed as planned.
• Women of childbearing potential who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy throughout treatment and for 5 months after its completion.
• Condition after organ transplantation

Sponsors & Collaborators

• Maria Sklodowska-Curie National Research Institute of Oncology: lead

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Uterine Cervical Neoplasms; Melanoma; Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Sławomir Blamek, MD, PhD, MBA

  Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sławomir Blamek, MD, PhD, MBA

CONTACT

+48322788052; slawomir.blamek@gliwice.nio.gov.pl

Marzena Gawkowska, MD, PhD

CONTACT

+48322788625; marzena.gawkowska@gliwice.nio.gov.pl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2025
• First Posted: May 16, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: May 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR