In the current study, biomarkers for tumor and immune response during radium-223 are evaluated, thereby potentially contributing to a better understanding of immune responses during radium-223 and the rational design of future treatment strategies…
ID
Bron
Verkorte titel
Aandoening
- Voortplantingsorgaan- en urogenitale neoplasmata, geslacht niet-gespecificeerd NEG
Aandoening
Prostate cancer, castration resistant prostate cancer, mCRPC, radium-223, biomarker, immune response. Prostaatkanker, castratieresistente prostaatkanker, radium-223, biomarker, immuunrespons.
Betreft onderzoek met
Ondersteuning
Onderzoeksproduct en/of interventie
- Overige
Uitkomstmaten
Primaire uitkomstmaten
1. Exploratory analysis of multiple biomarkers in relation to failure-free survival, defined as time to next line of treatment, best supportive care or death. Next line of treatment or best supportive care will be started upon clinical, biochemical and/or radiological signs of progression according to the PCWG3 criteria.
2. Exploratory analysis of the immune response during radium-223 treatment in relation to failure-free survival as defined above.
Achtergrond van het onderzoek
Based on the survival results of a randomized phase 3 trial, the European Medicines Agency (EMA) and Committee for the Assessment of Oncological Medicines (‘Commissie BOM’) have approved radium-223 for the treatment of metastatic castration resistant prostate cancer (mCRPC) with bone metastases only. As traditional parameters, including PSA, fail in (early) response evaluation, other parameters are needed to guide treatment planning in mCRPC patients. As the efficacy of immunotherapy is limited in mCRPC and radium-223 may initiate an immune response by activation of CD8 T lymphocytes, further understanding is required for the rational development of combination strategies, including those with radium-223.
Doel van het onderzoek
In the current study, biomarkers for tumor and immune response during radium-223 are evaluated, thereby potentially contributing to a better understanding of immune responses during radium-223 and the rational design of future treatment strategies combining radium-233 with immunotherapy.
We hypothesize that:
1) Multidimensional biomarker collection enhances our understanding of tumor responses during radium-223, thereby potentially identifying biomarkers for early response.
2) Radium-223 induces DNA damage, resulting in immunogenic cell death and activation of the immune system, thereby making tumors more prone to immunotherapy.
Onderzoeksopzet
- Baseline: week -1
- During treatment: week 3, 7, 11, 15, 19
- End of treatment: week 24
- During follow-up: every 12 weeks
- At progression of disease
Onderzoeksproduct en/of interventie
Patients will be treated with radium-223 according to standard of care. Prior and during treatment, multi-parametric biomarkers will be collected. These biomarkers are obtained from blood samples, imaging and tissue.
Blood samples:
- Conventional markers (PSA, ALP, LDH)
- Circulating tumor cells
- Circulating tumor derived DNA
- Immune cells and markers
Imaging:
- Conventional imaging (CT and bone scintigraphy)
- [68Ga]PSMA PET-CT
- [89Zr]atezolizumab PET-CT
Tissue (bone biopsy):
- Whole genome sequencing, focusing on mutational and immune profiling data.
- In situ multiplex immune fluorescence of FFPE using automated quantitative pathology imaging.
Algemeen / deelnemers
Wetenschappers
Leeftijd
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
• Age ≥ 18 years
• Histologically confirmed, progressive prostate cancer during ADT. Castration-resistant disease is defined as a serum testosterone level of 50 ng per deciliter or lower (≤1.7 nmol per liter) after bilateral orchiectomy or during maintenance treatment consisting of androgen-ablation therapy with a luteinizing hormone–releasing hormone agonist.
• Baseline PSA level of ≥ 2 ng per milliliter with evidence of progressively increasing PSA values (two consecutive increases over the previous reference value) • Prior treatment with at least two other approved agents for metastatic prostate cancer, unless the patient is not able and/or willing to receive other treatments.
• Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1 (on a scale of 0 to 5, with 0 indicating no symptoms and full activity and higher scores indicating greater functional compromise)
• Life expectancy of 6 months or longer
• Adequate hematologic, renal, and liver function, including trombocytes >100x109/L, granulocytes >1.5x109/L, Hb >6.2 mmol/L.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
• Prior chemotherapy, other than docetaxel.
• Previous hemibody external radiotherapy or systemic radiotherapy with radioisotopes within the previous 24 weeks.
• A blood transfusion or use of erythropoietin-stimulating agents within the previous 4 weeks
• Pathological lymphadenopathy > 1.5 cm in the short-axis diameter on CT or MRI. [68Ga]-PSMA positive lymph nodes at baseline are allowed.
• A history of presence of visceral metastases on CT or MRI. Patients with [68Ga]-PSMA positive lesions that are highly suspected for visceral metastases and are retrospectively visible on CT or MRI should be excluded as well.
• Imminent or established spinal cord compression on CT or MRI.
• A second active malignancy.
Opzet
Deelname
Voornemen beschikbaar stellen Individuele Patiënten Data (IPD)
Opgevolgd door onderstaande (mogelijk meer actuele) registratie
Andere (mogelijk minder actuele) registraties in dit register
Geen registraties gevonden.
In overige registers
| Register | ID |
|---|---|
| NTR-new | NL7380 |
| NTR-old | NTR7588 |
| CCMO | NL66323.078.18 |
| OMON | NL-OMON55470 |