Clinical Research Directory

Study of RYZ101 Compared With SOC in Pts w Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy

This study aims to determine the safety, pharmacokinetics (PK) and recommended Phase 3 dose (RP3D) of RYZ101 in Part 1, and the safety, efficacy, and PK of RYZ101 compared with investigator-selected standard of care (SoC) therapy in Part 2 in subjects with inoperable, advanced, well-differentiated, somatostatin receptor expressing (SSTR+) gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have progressed following treatment with Lutetium 177-labelled somatostatin analogue (177Lu-SSA) therapy, such as 177Lu-DOTATATE or 177Lu-DOTATOC (177Lu-DOTATATE/TOC), or 177Lu-high affinity \[HA\]-DOTATATE.

Carcinoid Syndrome Efficacy Study Featuring an Oral Daily Paltusotine Regimen

A Phase 3, randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of paltusotine treatment vs placebo as well as the long-term safety of paltusotine in adults with carcinoid syndrome due to well-differentiated neuroendocrine tumors. The purpose of this study is to continue the evaluation of the safety, efficacy, and pharmacokinetics (PK) of paltusotine in participants with carcinoid syndrome.

Virtual Reality for GI Cancer Pain to Improve Patient Reported Outcomes

Patients with digestive tract malignancy often experience severe and unremitting abdominal pain that negatively affects physical, emotional, and social function, as well as health related quality of life (HRQOL). Therapeutic virtual reality (VR) has emerged as a promising and evidence-based treatment modality for cancer pain. Users of VR wear a pair of goggles with a close-proximity screen in front of the eyes that creates a sensation of being transported into lifelike, three-dimensional worlds. To date, VR has been limited to short-term clinical trials for cancer pain. Moreover, limited research exists on theory-based VR modalities beyond mere distraction, such as VR that employs acceptance and commitment therapy (ACT) with components of biofeedback and mindfulness. To bridge these gaps, this study seeks to: (1) assess the impact of immersive VR on patient-reported outcomes (PROs), including pain, activity metrics, and opioid use among patients with visceral pain from a digestive tract malignancy; (2) assess differences in PROs, activity metrics, and opioid use between skills-based VR therapy vs. distraction VR therapy; and (3) determine patient-level predictors of VR treatment response in visceral cancer pain. To address these aims, the study will measure PROs and opioid use in 360 patients randomized among 3 groups and follow them for 60 days after enrollment: (1) an enhanced VR group receiving skills-based VR; (2) a distraction-based VR group receiving patient-selected VR videos; and (3) a VR sham control group using a VR headset with 2-D content. The results will inform best practices for the implementation of VR for visceral cancer pain management and guide selection of patient-tailored experiences.

An Investigational Scan (Dual Energy CT) in Detecting Gastrointestinal Carcinoid Tumors

This trial studies the use of a special type of computed (CT) scan called dual energy CT in detecting gastrointestinal carcinoid tumors. CT is an imaging technique that uses x-rays and a computer to create images of areas inside the body. Dual energy computed tomography is a technique used during routine CT scans to help obtain and process the image after the scan is complete. Doctors want to learn if dual energy computed tomography can help improve the detection of carcinoid tumors during routine CT scans.

Trial of an Alternative Cabozantinib Dosing Schedule in Metastatic Renal Cell Carcinoma and Neuroendocrine Tumors

This is a multi-site, three-cohort phase II trial of cabozantinib for IMDC all-risk frontline metastatic renal cell carcinoma (mRCC) patients OR any line mRCC patients who have not previously been treated with cabozantinib, and patients with pancreatic or extra-pancreatic neuroendocrine tumors.

IMMUNORARE5: A National Platform of 5 Academic Phase II Trials Coordinated by Lyon University Hospital to Assess the Safety and the Efficacy of the IMMUNOtherapy With Domvanalimab + Zimberelimab Combination in Patients With Advanced RARE Cancers

Immune checkpoint inhibitors (ICI) have revolutionized the management of advanced cancers. However, most rare cancers have been excluded from this progress due to the lack of clinical trials involving these diseases. After the standard first-line treatment, there are no other validated treatments for most of them. The management of these patients in ≥ 2nd line treatment relies on historic poorly effective regimens. This creates an inequity between patients with frequent cancers beneficiating from medical progresses and approvals of innovative drugs, and patients with rare cancers are still treated with old and toxic drugs. Few available data on case reports and early phase studies indicate a beneficial role of the immunotherapy in rare cancers. The investigators assume that the combination of Domvanalimab and Zimberelimab is more effective than historical standard treatments in patients with 5 types of advanced rare cancers, after failure of at least one line of standard treatment in the advanced setting: * Cohort 1: Peritoneal Mesotheliomas (PM) * Cohort 2: Gestational Trophoblastic Tumors (GTT) * Cohort 3: B3 Thymomas and Thymic Carcinomas (TET) * Cohort 4: Refractory Thyroid Carcinomas (ATC) * Cohort 5: GEP-NET and carcinoid tumors (GEP-NET (Gastroenteropancreatic neuroendocrine tumors)/TCT (Thoracic carcinoid tumor)/UP-NET (Neuroendocrine tumor of unknown primary)) The primary objective is to assess the efficacy of the combination of Domvanalimab and Zimberelimab in terms of progression-free survival rate at 24 weeks (for cohorts 1,3,5), successful hCG (Human Chorionic Gonadotropin) normalisation rate at 24 weeks for cohort 2 and survival rate for cohort 4. The secondary objectives are to assess the efficacy of the combination of anti-TIGIT (T cell Immunoreceptor with Ig and ITIM domains) and anti-PD-1 (Programmed Death-1) immunotherapies in terms of overall response rate, progression-free survival (cohort 1-3 and 5), resistance-free survival (cohort 2), overall survival (cohorts 1-3 and 5), duration of the response (cohorts 1-3 and 5); and to assess the tolerability of the doublet of immunotherapy in terms of adverse events. Patients will be treated until disease progression or alternatively 2 years in case of complete response (upon discussion with the coordinator of the study, the coordinator of the cohort and the investigator), unacceptable toxicity, or death. At the end of treatment, patients will be followed up for at least 1 year. IMMUNORARE5 is composed of five independent open-label national multicenter single-arm phase II trials, sponsored by Lyon University Hospital, led in collaboration with the corresponding French national reference centers, with a centralized coordination by a dedicated team. Each phase II trial is designed as a two-stage Simon design, with early termination for futility. For each cohort, a null hypothesis (H0) and an alternative hypotheses (H1) regarding the percentages of patients with success has been defined, with 5% one-sided alpha level and 80% power. The trial will be conducted in 15 French Centers with an inclusion period of 36 months

Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158)

In this study, participants with multiple types of advanced (unresectable and/or metastatic) solid tumors who have progressed on standard of care therapy will be treated with pembrolizumab (MK-3475).

ALG-LungCancerRegistry (SAFRO2202)

SAFRO 2202 ALG-Lung Cancer Registry is a prospective, multicenter, non-interventional observational study conducted across 21 public and university hospitals in Algeria. The objective is to characterize the epidemiological, clinical, pathological, molecular, and therapeutic features of patients diagnosed with lung cancer, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and carcinoid tumors. Eligible participants are adults aged 18 years or older, diagnosed at the time of inclusion or within the previous 12 months, and fully managed in oncology or pulmonology departments. Data are collected during routine clinical care and recorded in a secure electronic case report form (eCRF). No protocol-mandated interventions or study-specific visits are required. The study plans to enroll approximately 1,500 patients per year over a 30-month period. Primary outcomes include demographic and clinical profiles, tumor histology, molecular markers, staging at diagnosis, and treatment strategies (surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy). Secondary outcomes include treatment-related toxicities, objective response rate (ORR), progression-free survival (PFS), time to treatment discontinuation (TTD), and overall survival (OS). The findings from this registry will provide real-world evidence to support national health planning, improve lung cancer management, and guide future clinical and public health initiatives in Algeria.

Study of RYZ401 in Subjects With Solid Tumors Expressing SSTRs.

The primary objectives are to determine the recommended Phase 2 dose (RP2D) and optimal treatment regimen, characterize safety and tolerability, and evaluate preliminary efficacy of RYZ401 in subjects with NETs and other selected solid tumors expressing SSTRs.

Personalized PRRT of Neuroendocrine Tumors

In this study, peptide receptor radionuclide therapy (PRRT) with 177Lu-Octreotate (LuTate) will be personalized, i.e. administered activity of LuTate will be tailored for each patient to maximize absorbed radiation dose to tumor, while limiting that to healthy organs. The purpose of this study is to: * Assess the objective (radiological), symptomatic and biochemical response rates following an induction course of personalized PRRT; * Assess the overall, the disease-specific, and the progression-free survival following P-PRRT; * Correlate therapeutic response and survival with tumor absorbed radiation dose; * Evaluate the acute, subacute and chronic adverse events following P-PRRT; * Correlate toxicity (i.e. occurence and severity of adverse events) with absorbed radiation doses to organs at risk; * Optimize the quantitative SPECT imaging-based dosimetry methods in a subset of 20 patients (sub-study funded by the Canadian Institutes of Health Research). This study also has a compassionate purpose, which is to provide access to PRRT to patients.

SwissNET - a Registry for Neuroendocrine Tumours in Switzerland

Gastroentero-pancreatic neuroendocrine tumours (GEP-NETs) are regarded as a fairly rare disease. They are derived from the neuroendocrine system of the gastrointestinal tract and the pancreas and share common clinical features. So far, there is still uncertainty about the cell biology and mechanistic regulation of these tumours. Therefore targeted treatment is limited and management challenging. Treatment options include surgery, medical and ablative therapy, and more recently peptide-receptor radionuclide therapy. In order to better understand the characteristics of GEP-NETs and to evaluate treatment strategies, the SwissNET registry aims at the collection of data from patients presenting with a GEP-NET in Switzerland. Data will be entered prospectively and anonymized in a specifically designed database after the patient has given informed consent. All hospitals and general practitioners are invited to report on patients with a GEP-NET diagnosis and to participate to the registry. Data will be evaluated within regular time frames, focussing on types of GEP-NETs, treatment modalities and patient outcomes (e.g. mortality, hospitalisation rate), thereby contributing to the better understanding of these tumours.