Clinical Trials

This Phase I/II clinical trial was conducted to prospectively evaluate the acute, early late, and late gastrointestinal (GI), genitourinary (GU), and sexual toxicities associated with a combined hypofractionated external beam radiation therapy (EBRT) and high dose-rate brachytherapy (HDR-BT) protocol in patients with unfavourable intermediate- to high-risk organ-confined prostate cancer who did not require pelvic irradiation.

The treatment regimen included 36 Gy of EBRT delivered in 12 fractions of 3 Gy, followed by a single 14 Gy fraction of HDR-BT. The study was based on evidence from dose-escalated trials showing improved progression-free and metastasis-free survival in prostate cancer, as well as radiobiological data suggesting the tumor’s low α/β ratio favors hypofractionation.

In addition to assessing treatment-related toxicities, the study evaluated overall survival (OS), prostate cancer-specific survival (PCSS), disease-free survival (DFS), and metastasis-free survival (MFS). Quality of life (QoL), treatment-related symptoms, and the perceived convenience of care were also comprehensively analyzed. The trial further investigated the role of molecular imaging—specifically 18F-PSMA-PET/CT—in monitoring treatment response and disease progression.

Eligible participants had histopathologically confirmed prostate adenocarcinoma and were classified as having unfavourable intermediate- or high-risk disease based on NCCN guidelines (version 3.2020), with no evidence of regional or distant metastases. Conventional staging included multiparametric prostate MRI, CT abdomen/pelvis, and bone scintigraphy, in addition to the PSMA-PET/CT.

All patients received androgen deprivation therapy (ADT) according to institutional protocols. HDR-BT was delivered using ultrasound-guided interstitial multicatheter implantation. Patients consenting to biospecimen collection also provided tumour tissue from initial core biopsies and serum samples for translational research.

The trial aimed to recruit 40 patients over a two-year period, with an expected accrual rate of 2 patients per month in the first year, increasing to 3–4 patients per month in the second year.

This study aimed to assess the safety, pharmacokinetics, and immunogenicity of a fixed-dose intravenous combination (IV FDC) of tiragolumab and atezolizumab in participants with histologically confirmed PD-L1-selected solid tumors. Eligible participants had locally advanced, recurrent, or metastatic disease, and an investigational treatment combining an anti-PD-L1 antibody was considered a suitable therapeutic option for them.

Every year, about 58,000 and 500 men in Germany and Cyprus, repsectively, are newly diagnosed with this tumor. This demographic development must be considered in the diagnosis and treatment of prostate cancer.

Based on the Gleason score, TNM stage and PSA serum concentration, localized PCa is divided into 3 risk groups according to NCCN: low-, intermediate- and high-risk PCa. The standard therapy for low- to intermediate-risk PCa patients is prostatectomy or radiotherapy (RTx) in which the entire gland is treated with a homogeneous dose. Alternatively, the PCa patient can be actively monitored. Patients with low-risk and low-intermediate-risk PCA have PCA-specific mortality of 99.4%, 100% and 100% when treated surgery or percutaneous radiotherapy or monitored with active surveillance. PCa progression occurs in 21%, 8% and 8% of patients when treated with active surveillance, surgery or percutaneous radiotherapy. Percutaneous radiotherapy and surgery may lead to a reduction in quality of life in this patient population (especially due to GI toxicity, GU toxicity and erectile dysfunction). Ten years after percutaneous radiotherapy or surgery, 33.3% and 38.5% of patients with high-risk PCa develop metastasis of tumor disease. Since a dose-response relationship has been described for primary PCa, tumor control in primary PCa is dependent on the administered radiation dose. Martinez et al. were able to show that a dose of > 100 Gy (EQD2, α/β= 1.2 Gy) exerts a significant influence on recurrence-free survival in intermediate and high-risk patients.

Radiotherapy in patients with PCa can either be carried out solely from the outside (percutaneous radiotherapy, EBRT). An alternative is radiation from the inside (brachytherapy, BT). The BT is either a high-dose rate (HDR) or a low-dose rate (LDR) BT. Especially in patients with intermediate and high-risk PCa, new studies have shown that a combined use of BT, EBRT and, if necessary, antihormonal therapy is superior to EBRT or surgery alone. A possible cause of this effect is the application of an increased radiation dose (compared to EBRT alone), the coverage of periprostatic tissue and lymph node pathways with radiation dose (compared to surgery) and the use of antihormonal therapy (compared to surgery). Nevertheless, over 25% of high-risk patients develop a biochemical recurrence after combined EBRT and BT and about 10% of patients die from their tumor disease. In addition, Rodda et al. reported that the combined use of BT and percutaneous EBRT may lead to an increase in toxicity. Accordingly, it would be important to select patients who would not benefit from a combined EBRT and BT (for example, patients with low intermediate-risk PCA). Similarly, the targeted inhibition of proteins or protein signaling cascades could cause tumor cells to react more sensitively to radiotherapy. So far, it is not known what influence the combined application of EBRT and BT has on the RNA and protein expression of PCa. Furthermore, it is not yet known whether certain RNA and/or protein patterns have an influence on the further development or therapy response after primary EBRT + BT in patients with PCa.

This study will enrol 50 patients who have been diagnosed with prostate cancer. This study will prospectively compare two very promising advanced medical imaging modalities: MRI-RSI and PSMA PET, with the method that is typically used today, mpMRI, for detecting and defining tumour boundaries in patients with primary prostate cancer.

The patients in this study all receive PSMA/PET which is the standard practice/examination for this group of patients in Cyprus. What is innovative in this study is MRI/RSI which is a special MRI sequence that requires neither additional equipment nor any contrast agent. The patient simply stays 10 minutes longer in the MRI to have the sequence performed.

Male patients with histologically confirmed primary prostate cancer who meet the inclusion criteria will be invited to participate in the study at their initial meeting with their treating radiotherapist and/or oncologist.

This clinical study aims to evaluate whether personalized radiotherapy—guided by advanced medical imaging and using local dose escalation within the prostate through stereotactic radiotherapy—can improve recurrence-free survival compared to conventional fractionated radiotherapy in patients with primary prostate cancer. Additionally, the reduction in the number of radiotherapy sessions (5 sessions with stereotactic radiotherapy versus 20 sessions with conventional radiotherapy) is expected to decrease patient discomfort and improve treatment convenience.

Specifically, patients diagnosed with prostate cancer at moderate to high/very high risk, with no evidence of metastases confirmed by PSMA PET/CT imaging, will be randomly assigned to one of two groups:

1. Intervention group: Patients will receive stereotactic prostate radiotherapy with targeted dose escalation to the dominant cancer focus over 5 treatment sessions.

2. Control group: Patients will undergo conventional fractionated radiotherapy delivered in 20 sessions.

Patient recruitment will be conducted by specialist radiation oncologists at the German Oncology Center, who will enroll eligible patients following written informed consent. This randomized Phase III clinical trial is designed to enroll 374 patients over a total duration of 87 months—from the first patient’s enrollment to the last participant’s final visit. Patient recruitment is planned to last 36 months within this timeframe. The study is expected to conclude by the third quarter of 2029.

Technical advances in radiotherapy (RT) treatment planning and delivery have substantially changed RT concepts for primary prostate cancer (PCa) by (i) enabling a of treatment time and by (ii) enabling a safe delivery of high RT doses. Several studies proposed a dose-response relationship for patients with primary prostate cancer (PCa) and especially in patients with high-risk features a dose escalation should lead to improved tumor control. In parallel to the improvements in RT techniques, diagnostic imaging techniques like multiparametric magnetic resonance imaging (mpMRI) and positron-emission tomography (PET) evolved and enable an accurate staging of the patients for the first time. Additionally, artificial intelligence (AI) based analysis of tumor biopsy samples in combination with clinical parameters might lead to models (so called MMAI) which predict the RT treatment response in primary PCa patients better than the use of sole clinical parameters. The patients in the HypoPro study will undergo most modern medical imaging for staging (prostate-specific membrane antigen PET and mpMRI) in combination with MMAI classifiers. Patients with localized PCa and a conventional high-risk but MMAI low-/intermediate-risk profile will receive a tailored treatment: (i) ultra-hypofractionated RT / stereotactic body RT (SBRT) and high-dose rate brachytherapy (HDR BT) to achieve a dose-escalation on the prostatic gland. (ii) In parallel the time of androgen deprivation therapy (ADT) administration will be reduced from >18 months to 12 months. We suspect the same tumor control in terms of disease-free survival (DFS) 5 years after treatment and an excellent quality of life (QOL) in comparison with historic comparison groups.

Europe and radiation therapy (RT) is a main treatment option. For primary high-risk localized PCa patients, NCCNv4.2023 guidelines recommend normo- or hypofractionated RT to the prostate ± the elective pelvic lymphatics and systemic treatment in terms of ADT. Although the standard of care, the benefit of this therapy regimen is controversially discussed: the benefit of (i) an RT dose escalation using brachytherapy (2) or focal dose escalated RT(3) or (ii) an elective RT of the pelvic lymph nodes (1) is not finally proven yet. In parallel, first studies proposed a reduction in treatment fractions in terms of ultrahypofractionated RT (UHF-RT) (4). The aim of this prospective, single-arm phase II study is the individualization of RT for patients with high-risk localized PCa based on MMAI. All patients will receive the current standard of care: (i) a dose escalation to the prostate via HDR brachytherapy, (ii) two years of ADT and (iii) whole-pelvis UHF-RT (5 fractions). For the HypoElect patients we expect no significant differences in toxicity rates compared to the randomized controlled POP-RT trial (1) which treated the patients with moderatelyhypofractionated RT to the prostate and the elective pelvic lymph nodes in parallel to 24 months of ADT. Secondary endpoints like relapse free survival, metastatic free survival, prostate cancer survival and overall survival will depict the oncologic efficacy in this patient cohort. Thus, the safety and oncologic outcome results of this study might be the first in this highly selected treatment group: NCCN high-risk, PSMA PET cN0/cM0 and MMAI high-risk. Considering the epidemiological importance of the PCa these results could have a significant socio economic impact. In parallel a translational research program will address the identification of novel biomarkers to predict the treatment outcome.

In patients with estrogen receptor positive (ER+) human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer, the administration of adjuvant chemotherapy and endocrine treatment (ET) substantially reduces the recurrence rates. However, despite adjuvant systemic treatment, recurrences occur up to 20 years.

ctDNA may be a useful biomarker after potentially curative treatment to identify individuals at high risk of relapse. The early diagnosis of recurrence by ctDNA analysis could allow effective therapies to be introduced at time when disease burden is still minimal.

Elacestrant, a new oral selective estrogen receptor degrader, has shown significant clinical benefit in patients with ER+/HER2- advanced or metastatic breast cancer following progression on a CDK4/6-inhibitor and could be used at time of ctDNA relapse to delay the occurrence of distant metastasis.

Primary objective

-To evaluate whether elacestrant can delay occurrence of distant metastasis or death when compared to standard endocrine therapy in ER+/HER2- breast cancer patients with ctDNA-relapse.

Secondary objectives

-To evaluate invasive disease-free survival (iDFS), relapse-free survival (RFS) and overall survival (OS) between the 2 treatment arms

-To characterize the safety and the tolerability of the 2 treatment arms

-To establish the patient-reported tolerability profile in each treatment arm

-To compare the patient-reported benefit between the two treatment arms

Exploratory objectives

-To evaluate associations between ctDNA elimination at month 1 and DMFS according to treatment arm

-To evaluate associations between ctDNA elimination at month 4 and distant metastasis free survival (DMFS) according to treatment arm

-To correlate ctDNA (as categorical variable) kinetics with DMFS, iDFS, RFS and OS according to treatment arm

-To identify plasma circulating biomarkers associated with benefit from elacestrant