Clear Cell Renal Cell Carcinoma, Malignant Melanoma, Triple Negative Breast Cancer, Uterine Cervical Cancer, Uterine Corpus Cancer
Conditions
Keywords
spatially fractionated radiotherapy, immunotherapy, immuno-PET, proteomics, signaling pathways
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.
Interventions
DIAGNOSTIC_TESTBaseline 89-Zr Pembrolizumab Immuno PET-CT
Diagnostic imaging with novel radiotracer - drug (Pembrolizumab) labeled with zirconium-89
DIAGNOSTIC_TESTProteomic assay
Assessment of the proteomic profile before and periodically after treatment
DIAGNOSTIC_TESTFollow-up 89-Zr Pembrolizumab Immuno PET-CT
Diagnostic imaging with novel radiotracer - drug (Pembrolizumab) labeled with zirconium-89 after radiotherapy performed in patients who are not treated with immunotherapy
Sponsors
Maria Sklodowska-Curie National Research Institute of Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in expression of PD-1 receptors expressed as a ratio of SUV values | one year | 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 |
| Change in number of areas with PD-1 receptors expressed as number of lesions | one year | 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 |
| Change of proteome expression profile after treatment expressed in NPX (Normalized Protein eXpression) values | one year | 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. |
Contacts
Primary ContactSławomir Blamek, MD, PhD, MBA
Backup ContactMarzena Gawkowska, MD, PhD
Outcome results
None listed