Clinical trial NCT06976021: Immune PET and Proteomics for the Assessment of Response to Spatially Fractionated or Palliative Radiotherapy With or Without Immunotherapy
Official title: Immune PET and Proteomics for the Assessment of Response to Spatially Fractionated or Palliative Radiotherapy With or Without Immunotherapy Ocena Efektu immunomodulującego Radioterapii Paliatywnej, w Tym Radioterapii z Przestrzennym zróżnicowaniem Dawki, Podanej Samodzielnie Lub z immunoterapią, u Chorych którzy Wyczerpali możliwość Leczenia Systemowego i Radioterapii Radykalnej, Przy Wykorzystaniu Immuno-PET i badań Proteomicznych
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
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
Lead sponsor: Maria Sklodowska-Curie National Research Institute of Oncology
Sponsor class: OTHER
First posted: 2025-05-16
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.


Eligibility criteria: Inclusion Criteria:

1. Pathologically confirmed diagnosis of clear cell renal cell carcinoma, melanoma, cervical cancer, endometrial cancer or triple negative breast cancer.
2. 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
3. General condition according to Karnofsky scale: 60-100
4. Patients with tumor (index lesion) larger than 5 cm in size that can be irradiated with either SHORT or SFRT technique (presence of other tumors that may be independently treated locally is not an exclusion criterion)
5. The tumor may be assessed using iRECIST
6. Age over 18 years
7. Granted written, informed consent to participate in the research experiment
8. No contraindications to treatment with Pembrolizumab (according to the information provided in the product characteristics).
9. Expected survival time over 6 months.

Exclusion criteria

1. Lack of consent to participate in the experiment
2. Contraindications to Pembrolizumab according to the product characteristics
3. Pregnancy and lactation
4. Inability of the patient to cooperate, including claustrophobia that prevents imaging tests from being performed as planned.
5. 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.
6. Condition after organ transplantation

Primary outcomes:
measure: Change in expression of PD-1 receptors expressed as a ratio of SUV values
timeFrame: one year
measure: Change in number of areas with PD-1 receptors expressed as number of lesions
timeFrame: one year
measure: Change of proteome expression profile after treatment expressed in NPX (Normalized Protein eXpression) values
timeFrame: one year
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch
name: Sławomir Blamek, MD, PhD, MBA
role: PRINCIPAL_INVESTIGATOR
References: