Clinical trials

This is a phase 1, open-label, multicentric study evaluating the safety, feasibility and efficacy of ODI-2001, a personnalized therapeutic cancer vaccine composed of DNA neoantigen vaccine, Modified Vaccinia virus Ankara (MVA) viral adjuvant and anti-CTLA4 (ipilimumab), in patients with metastatic or locally advanced colorectal or pancreatic cancer. The study includes a dose-escalation phase to determine the maximum tolerated dose (MTD) followed by an expansion phase to evaluate efficacy in terms of progression-free survival

This is a prospective, interventional, open-label, single-arm, multicenter pilot study evaluating the safety, tolerability and maximum tolerated dose (MTD) of splenic Selective Internal Radiation Therapy (SIRT) using TheraSphere in adult patietns with gastrointestinal cancer and chemotherapy-induced thrombocytopenia with splenomegaly

5 to 10% of cancers are due to the presence of a constitutional genetic alteration. It can be inherited from parents (family form) or by accident, in the first moments of life after fertilization (sporadic form). In both cases, this genetic alteration is constitutional and transmissible to descendants. It is hereditary. When an hereditary early form is suspected, several well-known genes generally involved in genetic predispositions to cancer are found by a technique called " gene panel ". However, this analysis does not always identify the genetic predisposing factors for cancer. New techniques called "high-throughput exome sequencing (SHD-E)", allow more than the analysis of the the gene panel. These analysis allow to identify alterations in other genes that could contribute to the development of cancer. The objective of the Ex²trican study is to show, from patients with early cancer (sporadic or familial form), that this approach to exome sequencing can be effective to identify new genetic risk of cancer, when the first panel analysis of genes is negative.

Cancers of the upper aerodigestive tract (UADT) are frequently treated with external beam radiotherapy, either alone or in combination with chemotherapy. Despite major advances achieved with intensity-modulated radiotherapy (IMRT/VMAT), irradiation of organs at risk (OARs) remains unavoidable and may lead to acute and late toxicities such as xerostomia, hyposalivation, swallowing disorders, and impaired quality of life. These toxicities are closely related to the dose delivered to salivary glands and other critical structures, and recommended OAR dose constraints are often exceeded to ensure adequate tumor coverage. Non-coplanar beam arrangements (NCBA) represent a potential strategy to further reduce radiation dose to OARs while maintaining equivalent target coverage. However, their clinical implementation has been limited due to technical complexity and the risk of collisions between the linear accelerator and the patient. The recent implementation of the opto-numerical solution MapRT® (VisionRT), based on three-dimensional modeling of the patient and the linear accelerator, allows safe and reliable identification of feasible non-coplanar beam trajectories. Retrospective dosimetric analyses conducted at our institution have demonstrated significant dose reductions to several OARs in UADT cancer patients treated with NCBA compared with conventional coplanar beam arrangements, without compromising tumor dose coverage. BaReTox is a prospective, open-label, randomized, single-center pilot trial designed to evaluate the clinical impact of non-coplanar beam radiotherapy on treatment-related toxicities and quality of life in patients with non-operated, non-metastatic squamous cell carcinoma of the oral cavity or oropharynx. Adult patients eligible for curative-intent bilateral radiotherapy, with known HPV (p16) status, are randomized to receive either standard coplanar radiotherapy (control arm) or non-coplanar radiotherapy (experimental arm), with or without concomitant chemotherapy. All patients receive a standard photobiomodulation protocol during radiotherapy. The primary objective is to compare the change in head and neck cancer-specific quality of life between baseline and three months after completion of radiotherapy, assessed using the EORTC QLQ-H\&N35 questionnaire, focusing on swallowing, social eating, and dry mouth domains. Secondary objectives include comparison of acute and late toxicities graded according to CTCAE version 5.0, assessment of salivary function by sialometry, evaluation of global and disease-specific quality of life over time, progression-free survival, feasibility of delivering non-coplanar radiotherapy, dosimetric impact on organs at risk, and evaluation of radiation-induced lymphopenia. This pilot study aims to provide clinical proof of concept for the benefit of non-coplanar beam radiotherapy in reducing toxicity and improving quality of life in patients with UADT cancers

The objective of this prospective multicenter study is to evaluate whether the analysis of immunological biomarkers present in circulating extracellular vesicles is associated with the response to anti-PD-1/PD-L1 treatments in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) or unresectable melanoma. Patients will receive standard-of-care treatment and will be followed according to routine clinical practice. The study involves the collection of four study-specific blood samples at different time points during follow-up, as well as the collection of standard immunohistochemistry results, thoraco-abdomino-pelvic CT scans, and tumor DNA genotyping analyses performed as part of routine care. The study aims to determine: * whether baseline biomarkers in extracellular vesicles are associated with response to anti-PD-1/PD-L1 treatment, * how these biomarkers change over the course of treatment, and * to provide exploratory data for the development of predictive immunological response signatures.

Monocentric study composed by 2 steps : 1. First step is a phase I with the aim of establish the recommended dose of mirdametinib administration (2 or 4 mg twice a day for 7 or 14 days per cycle for the 4 first of carboplatin/pemetrexed/pembrolizumab treatment) 2. Second step is a non comparative randomized (2:1) phase II trial testing the recommended dose of mirdametinib administration. The aim is the efficacy and safety of short course of mirdametinib treatment for the 4 first cycles of the carboplatin/pemetrexed/pembrolizumab treatment.

The "simple" analysis of the exome can determine somatic and constitutional mutations. The major challenge lies in the translation of sequencing data into clinically relevant information allowing the clinician to guide his decision-making A "complex" analysis of the exome would provide access to structural DNA data, concerning mutational signatures, tumor mutational load, analysis of large deletions, loss of heterozygosity as well as amplification of certain genes which may have an impact on the management of patients. No data available to date makes it possible to assess the clinical interest of the availability of its additional information resulting from a "complex" analysis compared to a "simple" analysis. The objective of the EXOMA2 study is to assess the proportion of patients for whom the proposed therapy is derived from its additional information (complex analysis) and would not have been possible with a classic exome analysis (simple analysis) . We hereby formulate the hypothesis that a "complex" analysis on a population presenting a metastatic or locally advanced disease treated early (from the 1st line of treatment) will make it possible to determine therapeutic indications which could not be discovered with a "simple" analysis.

Solid cancers are frequently treated with chemotherapies that target the DNA of cancer cells. It has recently come to light that bacteria are also the target of chemotherapies used in oncology. The results of current studies demonstrate the close link between the composition of the microbiota, the immune system, toxicity and the efficacy or otherwise of anti-cancer treatments. In this context, the study will measure the influence of treatment with anticancer molecules known to activate the bacterial SOS response on the emergence of antibiotic-resistant commensal bacteria in the gut microbiota of cancer patients. Furthermore, this study will investigate the existence of a close link between changes in the intestinal microbiota determined by the induction or non-induction of the SOS response, bacterial translocation, the integrity of the intestinal barrier and the antitumor immune response. The RAMA trial plans to collect stool and blood samples from two different cohorts of patients: * Unexposed cohort: patients receiving anti-cancer treatment that does not induce bacterial SOS response. * Exposed cohort: patients receiving anti-cancer treatment inducing the bacterial SOS response. Patients' stools will be collected within 7 days of their first chemotherapy treatment and within 7 days of the 3rd chemotherapy cycle. Two blood samples will be taken at the same time as the stool samples. The results obtained from this prospective clinical research will then be investigated in two experimental laboratory models. The aim is to demonstrate that cytotoxic anticancer drugs promote the emergence of antibiotic-resistant commensal bacteria, by means of this large-scale study comprising a clinical component, which is the subject of the research presented in this protocol, combined with laboratory research components.

APACOL is a pilot, bicentric, randomised, open-label, prospective, category 2 study. The presence of colon cancer modifies blood lipid parameters which are likely to have an impact on the efficacy of anti-cancer treatments. Previous data support the hypothesis that appropriate physical activity could modify the blood lipid parameters involved in chemoresistance in patients with metastatic colorectal cancer. The aim of the APACOL study is to investigate the impact of modulating the frequency (volume per week) of physical activity recommended by INCa on the variation in lipid parameters involved in chemoresistance in patients with metastatic colon cancer, with a reference level of these lipid parameters in people without cancer provided by the participation of volunteers who are not ill. The expectations at the end of this study are an improvement in the patient's quality of life / an improvement in the tolerance and efficacy of the chemotherapy treatment / identification of the frequency of APAs needed to vary the lipid metabolism involved in chemoresistance.

The time taken to obtain the results of germline mutations in BRCA1 and BRCA2 has become a major issue in adapting the therapeutic management of patients, particularly those with breast cancer. The time taken to obtain the results of BRCA1/2 tests in routine laboratories with a view to personalised treatment can range from a few weeks to a few months. The waiting time required to obtain results is likely to cause stress and anxiety in cancer patients. The investigators hypothesise that ultra-rapid testing can reduce anxiety about patients' genetic status and improve their mental well-being. The main objective of this project is to compare the results obtained with an ultra-fast kit developed by O.N.T with those obtained with the current gold standard, NGS sequencing.

Currently, the EXOMA2 study (NCT04614480) offers earlier and more comprehensive exome analysis in the management of cancer patients than EXOMA. Based on the active EXOMA2 patient file, the INFOGene study offers the opportunity to study patient-physician communication, to assess patient preferences with regard to different information modalities concerning theranostic exome analysis, and to reflect on information modalities to ensure optimal patient comprehension of the information provided. The qualitative cross-sectional study includes a dual observational and interventional component involving cancer patients. The patients will come from the EXOMA 2 active file at Dijon University Hospital and the CGFL.

The patients eligible for the study are those treated by radiotherapy on Linac MRI for a mobile cancerous lesion (pancreas, liver, kidneys, adrenals, lung, adenopathy above or below the diaphragm ...). After signing the consent form, each patient will be randomized to one of two treatment arms: * Standard arm : Radiotherapy treatment with Linac MRI without non-magnetic shielding * Experimental arm : radiotherapy treatment with Linac MRI with non-magnetic screen The aim is to evaluate the effect of using a non-magnetic screen visible to the patient in the bunker during radiotherapy sessions delivered by Linac MRI on decreasing the ratio between the actual treatment time and the treatment time predicted by the machine.

The standard treatment of high-risk prostatic adenocarcinoma is based on pelvic-prostatic external radiotherapy combined with concomitant and adjunctive hormone therapy for a total of 3 years. Prostatic stereotactic radiotherapy in 5 sessions is a therapeutic option currently delivered and described in multiple cohorts of patients with a tolerance comparable to normo-fractional treatments. This therapeutic scheme makes it possible to deliver a higher equivalent biological dose than during a treatment carried out with a conventional fractionation. The results with a follow-up of 9 years are extremely encouraging and do not show any excess toxicity compared to other irradiation techniques. They confirm that urinary and digestive toxicities are acceptable. All these studies did not involve pelvic irradiation. Several trials have also demonstrated the feasibility of normofractionated pelvic irradiation associated with hypofractionated prostatic irradiation using an integrated boost technique. The primary objective is to evaluate, for localized high-risk prostate cancers (unfavorable intermediate or high risk), the rate of digestive and urinary toxicity cumulated at 3 months of the association of a pelvi-prostatic irradiation contracted in 5 sessions, with:To evaluate, for localized high-risk prostate cancers (unfavorable intermediate or high risk), the rate of digestive and urinary toxicity cumulated at 3 months of the association of a pelvi-prostatic irradiation contracted in 5 sessions, with: * a prostatic boost in brachytherapy with high dose rate (HDR) or * an integrated boost in stereotaxis (in case of contraindication to brachytherapy)

This study recommends the use of OnLife dietary supplement, which will be followed by a few day before the initiation of PACLITAXEL, for the prevention of PACLITAXEL induced neuropathy. OnLife will be continued one month after stopping chemotherapy. This would limit the number of PACLITAXEL dose reductions and premature interruptions of this chemotherapy, thus potentially improving the results in terms of antitumor efficacy, while improving the quality of life of patients treated with weekly PACLITAXEL.

Evaluate the efficacy of treatment FOLFORINOX 3 in first-line therapy for patients with locally advanced unresectable or metastatic pancreatic cancer.

Patients undergo three diagnostic PET scans: 18F-FDG PET scan / 18F-Choline PET scan and 68Ga-PSMA PET scan. Following the diagnostic PET scans, and if patients' eligibility for 177Lu-PSMA-617 IVR treatment is confirmed, SPECT acquisitions will be performed during the first treatment course at 5h, 24h, 4 days and 8 days for dosimetric control. The patient will then return to the nuclear medicine department to undergo SPECT/CT (3 FOV) acquisitions using the same methods as those presented above and recommended in the standard management at : D+24h post-injection, D+4d post-injection and D+8d post-injection No further research-specific acts or procedures will be performed at the end of the first treatment course. Continuity of treatment will be carried out in accordance with standard management and treatment requirements and modalities, as will clinical, biological and radiological follow-up.

This study aims to constitute a most complete biological collection for patients treated for localized or metastatic breast cancer (in different cohorts depending on the type of systemic treatment received), in order to describe the basal immune response of patients treated for a breast cancer according to the stage of the disease, but above all to study how the different systemic treatments used in the management of breast cancer modulate this immune response.

Hybrid positron emission tomography/computed tomography (PET/CT) has now become available to detect tumors in patients with multiple myeloma. The radioactive glucose 18F-fluorodeoxyglucose (FDG) is the most widely used tracer but findings suggest that PET/CT reveal more lesions when using FCH. In this study, FDG is compared with a more recent metabolic tracer, 18F-fluorocholine (FCH), for the detection of multiple myeloma lesions at time of initial extension assessment. The principal objective of this sudy is to compare the number of suspected hypermetabolic foci of myeloma detected by 18F-fluorocholine PET and by 18F-fluorodeoxyglucose PET during the initial extension assessment.