Clinical trials

At least 50% of patients with high-risk primary uveal melanoma will develop a recurrence following treatment of the primary tumour. Observation is currently the standard of care in the non-metastatic setting. Tebentafusp is the first agent proven to improve overall survival in patients with metastatic uveal melanoma in a randomized trial. Based on the results in the advanced setting, it is hypothesized that treatment with tebentafusp may reduce the risk of development of disease recurrence.

SPECTA is a quality assured platform for collecting clinicopathologically annotated biological material, imaging data, operative images, environmental assessment, questionnaires as well as patient-reported outcomes from cancer patients to support biospecimen-based translational research and clinical cancer research, including biomarker discovery to improve the understanding of tumor biology and cancer patients care.

Novel treatments are urgently needed for meningiomas progressing after local therapies (surgery, radiotherapy). So far, no effective systemic therapies are known in this situation. The LUMEN-1 trial will investigate in a prospective randomized trial the efficacy of the precision medicine "theranostic" concept of combining diagnostic patient selection using PET-based molecular imaging and target-specific therapeutic intervention using a systemically administered radioligand. The rationale for the LUMEN-1 trial is based on the following: (a) high somatostatin receptor (SSTR) expression in meningiomas, (b) wide-spread availability of clinically established SSTR-PET imaging, (c) proven efficacy of SSTR-targeting radioligand therapy using \[177Lu\]Lu-DOTATATE in another tumor type (neuroendocrine tumors), and (d) promising experiences with \[177Lu\]Lu-DOTATATE therapy in compassionate use applications and retrospective case series and interim results from one ongoing uncontrolled prospective trial in meningiomas. LUMEN-1 is the first randomized clinical trial to investigate \[177Lu\]Lu-DOTATATE therapy in refractory meningioma and may open new avenues for treatment and research in this area.

Despite comprehensive multimodal treatment of newly diagnosed glioblastoma, almost all patients suffer from tumour relapse. Currently, no standard of care exists to treat these tumour relapses. Treatment options include repeated surgery (if feasible), systemic therapy (bevacizumab, lomustine, temozolomide re-challenge), reirradiation and best supportive care. Currently, the superiority of combined chemoradiation versus chemotherapy alone remains unproven. Given that lomustine is the standard chemotherapeutic agent for the treatment of recurrent glioblastoma in Europe and the unclear efficacy of reirradiation, we want to explore whether combining lomustine and reirradiation may be a better treatment than lomustine alone. The results of the prospective randomized trial proposed here should demonstrate a significant improvement in overall survival when lomustine is combined with reirradiation in patients with recurrent glioblastoma compared to lomustine alone without adversely affecting quality of survival. The trial will be stopped based on overall survival in a preplanned futility and efficacy interim analysis.

This is a randomized, two-arm, comparative Phase II clinical trial designed to evaluate the difference in intracranial progression-free survival (iPFS) between two treatment strategies, assessed locally. Approximately 158 patients will be randomized in a 1:1 ratio. Will be included patients with pathology proven metastatic NSCLC without an actionable genomic alteration for which there is first line targeted treatment available and active asymptomatic brain metastasis (newly diagnosed or progressive). The primary objective is to compare iPFS between the two arms.

Background This study is for adults with advanced kidney cancer that has spread to other parts of the body and has continued to progress despite treatment with immunotherapy and targeted therapy. Unfortunately, treatment options at this stage of the disease are limited. The existing treatments' ability to work against cancer has not been fully looked into. Rationale The goal of this study is to examine if a new drug treatment called 177Lutetium-PSMA-617, hereafter referred as 177Lu-PSMA-617, which holds the active ingredient 177Lutetium-PSMA and has been used as a standard treatment for advanced prostate cancer since December 2022, can also help treat advanced kidney cancer. The drug 177Lu-PSMA-617 is being tested as an experimental treatment that targets a specific protein on cancer cells. This protein, known as prostate-specific membrane antigen (PSMA), is present on the surface of kidney cancer cells. Therefore, before the treatment begins, participants will undergo a PET (positron-emission tomography) scan to check if their kidney cancer cells express high levels of PSMA. This scan uses a small amount of radioactive material (in the form of 177Lutetium) to visualize the presence of PSMA on the cancer cells. Only participants who test positive for PSMA can take part in the study. In this approach, PSMA serves two purposes. First, it helps assess whether the cancer expresses this protein and allows 177Lu-PSMA-617 to specifically target and attach to the cancer cells. Second, 177Lu-PSMA-617 delivers a small amount of radiation directly to the tumour, which helps kill cancer cells while minimizing damage to normal cells. This type of treatment is known as a radiopharmaceutical. Objective The primary aims are to find out if 177Lu-PSMA-617 is useful against kidney cancer and to assess its safety. Throughout the study, participants will undergo several imaging assessments to check their disease and response to treatment. The study also includes the collection of tissue samples. Together with the information collected from the imaging assessments, this will allow further research into markers that may lead to earlier detection of tumour spread or help identify individuals who may benefit more from treatment with 177Lu-PSMA-617. Treatment All participants will receive 177Lu-PSMA-617 through an intravenous injection at a standard dose of 7,400 MBq (megabecquerel: a measure of radioactivity). Treatments will be administered approximately every six weeks, for a maximum of six times. Blood tests are done before and during treatment to check the participant's health and to detect any early side effects from the treatment. Different types of scans are performed before, during, and after 177Lu-PSMA-617 administration to check how well the treatment is working. After treatment ends, follow-up visits will be scheduled every six weeks during the first year. In the second year, your doctor will decide how often you need to come in for visits. These appointments are important for monitoring how the body continues to respond to the treatment. The entire study period will last approximately two years from the time of study entry. Participants The study will include approximately 56 participants who will be tested for PSMA expression, to obtain a minimum of 48 participants expressing PSMA entering the study. To qualify, participants must: * Be diagnosed with advanced kidney cancer previously treated with immunotherapy and targeted therapy. * Test positive for PSMA on a PET scan. * Be generally healthy and able to perform daily activities. * Be at least 18 years of age. Benefit-risk analysis The drug 177Lu-PSMA-617 has proven to work well in treating advanced prostate cancer and could be a promising new treatment possibility for kidney cancer, although this has not yet been shown. By joining this study, participants will contribute to valuable research to better understand kidney cancer and improve treatment options for future patients. Participating in this study offers a chance to try a new treatment, which might help people with advanced kidney cancer live longer and prevent the disease from getting worse, especially for those who have limited treatment options left after immunotherapy and targeted therapy. With all new treatments, there are possible risks and side effects associated with them. Side effects of the drug 177Lu-PSMA-617 may include feeling tired, nausea, dry mouth, loss of appetite, and changes in blood cells. While not all side effects are known yet, the study team will carefully follow participants for any side effects during and after treatment. It is important to understand that while the study is being done to provide new information, there are still some questions on the treatment's safety and how well it will work.

This is a randomized open-label multicentre phase III superiority study of the effect of adding SABR to the standard of care treatment pembrolizumab on progression free survival in patients with oligometastases of a squamous cell carcinoma of the head and neck (SCCHN), histological confirmation of the primary disease at first diagnosis, and PD-L1 CPS ≥1. After eligibility check and signing informed consent, all patients will be prospectively enrolled in a 1:1 ratio between current standard of care treatment (pembrolizumab, Arm 1) vs. SABR + standard of care treatment (Arm 2) to oligometastases. Any radical treatment to the synchronous primary/ recurrent primary tumor and/or involved cervical nodes (surgery or radiotherapy), as decided by the local tumor board/ treating physicians, should be completed prior to enrolment.Surgical removal of metastases is allowed for diagnostic purposes or for brain metastases, as long as these metastases count toward the total number of 5 and at least one metastasis is left for treatment with SABR. Such surgical procedures should be performed prior to enrolment.

The main goal of VIGOR is to demonstrate that vorasidenib maintenance therapy improves locally assessed progression-free survival (PFS) from enrolment compared to placebo in patients with IDH-mutant, CNS5 WHO Grade 2 or 3 astrocytoma following the completion of first-line chemoradiotherapy. The primary endpoint is Progression-free survival (PFS), as assessed locally from the date of enrolment using the RANO 2.0 criteria. In this a comparative, randomized (1:1), triple blinded, multicentre phase III superiority trial with one stopping rule for efficacy and futility after end of enrolment, participants in the experimental arm will receive vorasidenib orally once daily at a dose of 40 mg in continuous 28-day cycles while participants in the control arm will receive a matched oral placebo once daily in continuous 28-day cycles

This is a multicenter, randomized, open label phase lll trial to assess whether preoperative chemotherapy, as an adjunct to curative-intent surgery, improves the prognosis of high risk DDLPS (dedifferentiated Liposarcoma) and LMS (Leiomyosarcoma) patients as measured by disease free survival. After confirmation of eligibility criteria, patients will be randomized to either the standard arm or experimental arm.

This is an international, multi-center, randomised, open label, superiority phase III trial of elacestrant vs standard endocrine therapy in patients with ER+/HER2- breast cancer and ctDNA relapse. During the ctDNA screening phase, patients will be tested at different timepoints to detect the presence of ctDNA in their blood. Patients who are found to be ctDNA-positive and have no evidence of distant metastasis, will be randomised 1:1 between standard endocrine treatment (the same they were receiving when tested ctDNA positive) versus elacestrant, provided they meet all eligibility criteria. After completion of the protocol treatment period, treatment will be left at the discretion of the treating physician.

This international, multicenter, randomized (1:1), open-label phase II/III trial will evaluate the efficacy and safety of gilteritinib combined with azacitidine and venetoclax (experimental arm) versus standard "7+3" induction plus a FLT3inhibitor (quizartinib or midostaurin) (control arm) in newly diagnosed FLT3-ITD mutated AML patients eligible for intensive chemotherapy.

Every new classification depends on its prognostic power and on the type of treatment given. With the rapid evolution of diagnostic methods and the advance in new treatments, there is much less reliable information available on how patients with newly defined brain tumour entities should be treated and what to expect from the current treatments. The goal is to determine whether the new 2021 WHO classification, based on cIMPACT-NOW recommendations, results in more homogeneous patient groups than the old 2016 classification. Furthermore, it will help derive provisional guidelines on how patients with these newly defined tumour entities are best treated. These recommendations will be based on the experience of EORTC investigators with chosen treatments and their experience as reported in this data collection report.

This study addresses the global topic of treatment optimization, i.e. achieving similar benefit while reducing the duration of treatment, hence hoping to decrease the burden of side-effects, improve quality-of life and reduce resource utilization. The primary goal of de-escalation is to investigate whether using an intermittent regime results in a similar OS to continuous treatment.

The goal of this clinical trial is to evaluate single-fraction metastases-directed SBRT in the broader radiation oncology community and to compare its safety and efficacy profile with the current Standard of Care (SoC) of multiple-fraction SBRT in patients with oligometastatic disease of primary breast, prostate, NSCLC and colorectal cancer having all lesions that will be treated with radical radiotherapy amenable to single-fraction SBRT. The main question/hypothesis this clinical trial aims to answer is: \- Single-fraction SBRT has comparable outcomes as those obtained with multiple fraction SBRT, both in terms of safety and efficacy. Patients from the OligoCare cohort will be randomized to receive either single-fraction SBRT or the current SoC of multiple-fraction SBRT.

This is an open-label,multi-centre, phase 1b safety and feasibility study aiming to assess the safey and feasibility of bemarituzumab plus chemiotherapy (FLOT) for the peri-operative treatment of resectable gastroesophageal cancer. Following this neo-adjuvant part, patients should undergo surgery. Following surgery, patients will receive FLOT chemotherapy in combination with bemarituzumab. Imaging will be performed every 3 months for the first 2 years and thereafter every 6 months as per standard of care.

Standard treatment for patients with high-risk NMIBC (high-grade Ta, CIS, or any T1) consists of intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. However, BCG, even administered optimally, does not provide absolute protection and BCG failure is generally considered recurrence or progression during therapy. Patients who are BCG-unresponsive have a 20-40% risk for progression to muscle-invasive bladder cancer within 5 years, and a 50% risk of developing metastatic disease. For these patients, radical cystectomy with pelvic lymph node dissection and urinary diversion is the standard of care. However, many patients are unable to undergo radical cystectomy because of poor performance status and co-morbidities or decline to undergo surgery. Although, several phase II studies have shown promising results, none of the drugs are presently available in Europe. An alternative approach is to investigate a possible role for radiotherapy in good prognosis bladder cancer patients. As there is little existing data in NMIBC, the example of bladder preservation in MIBC will be used for guidance. We aim to evaluate the use of radiotherapy in patients with high-grade non-muscle-invasive bladder cancer who have BCG failure in a single-arm design as per FDA guidelines for this setting. The primary objective is to demonstrate that complete response to treatment 6 months post radiotherapy is seen in more than 30% of patients with BCG-unresponsive, non-muscle invasive carcinoma in situ bladder cancer, unfit or unwilling to undergo radical cystectomy. Patients with BCG unresponsive non-muscle-invasive bladder cancer according to the EAU guidelines will be treated 20 fractions of 2.75 Gy over 4 weeks with the use of radiosensitisers as per local guidelines. Cystoscopy and urine cytology assessments will be performed at 3 and 6 months from the start of radiotherapy. If either assessment is positive, bladder biopsies or TURBT are required. At the 6-month timepoint, biopsy or TURBT is mandatory. Disease assessments beyond 6 months will be at the treating urologist's discretion.

The primary objective is the collection of real-world data of cancer patients treated with radiotherapy, to support radiotherapy research and to provide evidence of the role of radiation oncology in a multidisciplinary approach. This is an open ended prospective non-interventional non-therapeutic multi-cohort study.

This study is a pragmatic international, multicenter, randomized, open label 3- arm trial of standard care vs. two pharmacological interventions: duloxetine or furosemide in patients with stage I-III ER+/HER2- early breast cancer with joint, muscle and/or bone pain caused by the endocrine therapy. The purpose of the BC-QOL trial is to find out whether treatment with duloxetine or furosemide, given while patients are on treatment with endocrine therapy, is active in improving quality of life (QoL), specifically by improving joint, muscle and/or bone pain caused by the endocrine therapy (based on EORTC QLQ-BR42 skeletal scale).

This is a randomized open-label multicentre Phase III superiority study of the effect of adding SBRT to the standard of care treatment on overall survival in patients with rare oligometastatic cancers. Patients will be randomized in a 1:1 ratio between current standard of care treatment vs. standard of care treatment + SBRT to all sites of known metastatic disease. The primary objective of this trial is to assess if the addition of stereotactic body radiotherapy (SBRT) to standard of care treatment improves overall survival (OS) as compared to standard of care treatment alone in patients with rare oligometastatic cancers.

The investigators aim to investigate a possible role for radiotherapy in good prognosis bladder cancer patients has been identified as a possible alternative to cystectomy, especially for patients non-eligible for surgery but has yet to be fully explored.

Cutaneous T-Cell Lymphoma (CTCL) has a chronic, relapsing course with patients undergoing multiple, consecutive therapies. Treatment aims at the clearance of skin disease, minimization of recurrence, prevention of disease progression and preservation of quality of life. The treatment of CTCL is primarily determined by the disease extent. Prolonged complete remissions have been obtained with skin-directed therapies in early stage Mycosis fungoides (MF) (IA-IIA), whereas advanced stages CTCL (IIB-IVB) are often refractory to treatment and, thus, have an unfavorable prognosis. Currently, there is no standard treatment option for CTCL, especially for advanced stages, and the optimal treatment sequence is still debated with a large variability in the therapeutic approach across countries. Patients with advanced-stage disease or refractory cutaneous CTCL should be treated with systemic therapies and, whenever possible, should be offered to participate in clinical trials. Currently, there is a urgent call for new treatments in CTCL with higher response rate and prolonged time to progression; In this study, we propose a very innovative treatment schedule in which mogamulizumab is used before Total Skin Electron Beam therapy (TSEB) for systemic disease control and as a maintenance treatment after skin-directed therapy. We hypothesize that our regimen will show a more manageable toxicity profile than a combination treatment and allow for a long-term mogamulizumab administration.

In this phase III study, the primary objective is to test with a one-sided significance of 5% whether for the treatment of small cell lung cancer (SCLC) patients, brain MRI surveillance alone is non-inferior in terms of overall survival compared to prophylactic cranial irradiation (PCI) combined with brain MRI surveillance in the entire study population.