Bligny, France

Digital Phenotyping in Women Over 70 Years of Age Treated for Breast Cancer With Any Type of Treatment

BACKGROUND: In metropolitan France in 2017, 58,968 new cases of breast cancer (BC) were estimated, of which 25,283 (46.7%) involved women older than 65 years. Older patients with cancer often present complex health needs, in particular because of the burden of comorbidities combined with the effects of aging, the cancer and its treatments. GrannyFit aims to use an activity tracker to identify and describe various digital profiles (physical activity, sleep) in women over 70 years of age treated de novo or recurrent (local or distant) BC. METHODS: GrannyFit is a prospective, national, multicenter, single-arm open-label study. It will include a total of 200 participants over the age of 70 years treated for de novo or recurrent (local or distant) BC. Participants will receive a Withing Steel activity tracker, which they will be asked to wear 24 h per day for 12 months. The principal assessments will be performed at baseline, at 6 months and at 12 months. The investigators will evaluate clinical (e.g. comorbidities), lifestyle, quality of life, fatigue, and physical activity parameters. All questionnaires will be completed on a REDCap form, via a secure internet link. DISCUSSION: GrannyFit will make it possible, through the use of an activity tracker, to visualize changes, over a one-year period, in the lifestyle of older BC patients. This study identify more precisely the unmets needs of this population and optimize their care through specific paths. This trial will also pave the way for interventional studies on physical activity and sleep interventions in this population.

REal World Data in LYmphoma and Survival in Adults

Evolution of the Therapeutic Care in Lung Cancer in France Since 2015 (ESME LC)

The database includes data related to patient demographics, tumor characteristics (diagnosis, histology, relapses, metastatic disease, etc.), treatments (dates, INN, route of administration, treatment protocols, reason for termination, etc.), and clinical events. Data is collected at each participating site by technicians who are specifically trained for the project using an electronic data collection (eDC) tool. Data imported into the final database are controlled, recoded, and harmonized before import according to the data management plan. All coding procedures are predefined by the data manager. There is no transmission of individual data; all data are centralized within each center using a shared anonymous format. All data is exclusively obtained retrospectively; no attempts are made to recover non available data from the patient's medical record by contacting healthcare providers or patients. ESME LC Data Platform aims to be a clinical and therapeutic database centralizing existing and available data from different sources used in the participating sites. Data do not contain any personal data on patients. In compliance with the authorization delivered by the French Data Protection agency to Unicancer, only aggregated statistical reports and publication are released.

Maintenance With OSE2101 Plus FOLFIRI, or FOLFIRI After FOLFIRINOX-based Induction Therapy in Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma

Current standard of care for patients with advanced pancreatic ductal adenocarcinoma (PDAC) is chemotherapy, preferential regimen being FOLFIRINOX (5FU, leucovorin, irinotecan, and oxaliplatin) in fit patients (PS 0-1, bilirubin < 1.5 ULN). The question of how and when the FOLFIRINOX regimen and doses can be deescalated after a period of disease control (i.e. maintenance therapy) remains unanswered. In routine practice, oxaliplatin is usually stopped after 6-8 cycles due to limiting neuropathy, and the fluoropyrimidine is continued, either alone or, more frequently, in combination with irinotecan (FOLFIRI regimen), until disease progression. Immune therapies have opened new opportunities in cancer therapy. However, results of immunotherapy in PDAC have been disappointing so far, with failure of checkpoint inhibitor monotherapies (anti-CTLA4 and anti-PD-L1 monoclonal antibodies [mAb]) in progressive advanced PDAC, while monovalent vaccines were demonstrated to be safe but with limited activity.

Sentinel Lymph Node After Neoadjuvant Chemotherapy in Breast Carcinoma

GANEA3 is a prospective multicenter diagnostic study assessing the benefit of targeting initial involved node in complement to SLND and breast tumor characteristics to predict axillary status after NAC. The diagnostic performances of this strategy will be primarily assessed by the decrease of the FNR with the combined strategy compared to SLND alone. The primary objective is to evaluate the interest of identifying, before NAC, the initial involved lymph node to improve the prediction of axillary status after NAC. The main secondary objectives are : - To assess the feasibility, at the time of the surgery, of the identification and resection of the initially involved lymph node, tagged with the metal clip before NAC ; - To evaluate the complications related to the setting up of the metal clip for the identification of a lymph node metastatic ; - To evaluate the interest and impact of immunohistochemical analysis of tagged lymph node and SLN ; Patients treated for a large early breast cancer (BC) needing NAC undergo axillary sonography assessment routinely performed to seek suspicious nodes. When several suspicious nodes are found only the worst is chosen. A fine needle aspiration is performed to allow cytological examination (biopsy is optional) of the suspicious node. In case of proven axillary involvement, the patient is informed about GANEA 3 study in order to be included. At this step the patient must accept the study and sign the consent form. The involved node is then tagged (with a metal clip) under sonography. In case of multiple suspicious nodes, the radiologist must choose the worst node in order to tag only one involved node. Then, then patients will perform their chemotherapy. The choice of NAC regimen is let at the discretion of each participating team. After NAC, breast tumor size and axillary assessment are performed. Breast and axillary surgery are performed during the same procedure, 4 to 6 weeks after completion of NAC. Breast surgery can be conservative or radical. All patients undergo the resection of the tagged axillary node, SLN biopsy and a complementary axillary lymphadenectomy.

Prognostic and Predictive Markers of Response to Treatment in Patients With Bile Duct Cancer: ACABi PRONOBIL Study

Bile duct cancers are a heterogeneous group of rare tumors with a poor prognosis. Surgery is the only curative modality for localized forms. Chemotherapy is the standard treatment in advanced forms. Identification of prognostic and predictive markers to better stratify patients and to guide therapeutic decisions is a major issue. It is retro-prospective (diagnosis between 2003 and 2021) and prospective (diagnosis between 2021 and 2030) multi-center, cohort study. Follow-up for 10 years from initial cancer diagnosis will be done. Follow-up is retrospective only for patients operated on or diagnosed in the past for more than 10 years, and retro-prospective for operated patients or diagnosed in the past for less than 10 years. The data collected for each patient are available during the life cycle of this clinical trial to fulfil an educational requirement (e.g. a doctoral thesis) upon request and authorization from the study committee and the study sponsor (GERCOR).

Study Comparing the Standard Administration of IO Versus the Same IO Administered Each 3 Months in Patients in Response After 6 Months of Standard IO

Immunotherapy (IO) is a rapidly expanding treatment for multiple metastatic cancers with improved survival for certain cancers. For currently approved immunotherapies such as PD-1 / PD-L1 inhibitors and anti-CTLA-4, the rhythm and duration of treatment are recommended until disease progression or unacceptable toxicity. However, the optimal duration of these treatments is currently unknown. No major dose-dependent effect of anti-PD-1 have been observed and whether the frequency of infusion of IO could improve response or maintain efficacy. Moreover, phase I studies have shown that saturation of the target (PD-1 or PD-L1) can persist far beyond the serum half-life of the IO and 3-monthly infusions of an anti-PD-1 antibody could potentially generate the same level of activity as infusions administered every 2 weeks. In silico modeling studies have suggested that alternate scheduling with IO couldn't compromise the efficacy of the treatment. Indeed, prolonged half-lives of IO drugs, time-varying clearance plus plasma concentrations far above the threshold associated with maximal target-engagement, suggest that the rhythm of administration of IO could be slowed down. Without substantial international data for responding patients, apart metastatic melanoma in complete response, patients and physicians are afraid of stopping treatment, by fear of relapse. Over-treatment with IO may be toxic and inefficient. The rising cost of cancer care in the era of immunotherapy is of great concern for public and private payers around the world. Chronic administration has important consequences for patients and health systems, with multiple medical visits and the risk of chronic, progressive and sometimes fatal toxicities induced by immunotherapy. This is a pragmatic and strategic study challenging the routine practice which compares for the first time in a randomized phase III study, the standard administration of IO versus the same agent administered each three months in patients with metastatic cancer in partial or complete response after 6 months of standard IO ( except melanoma in CR). If our hypothesis of non-inferiority of PFS with a reduced dose intensity of IO is verified, this could replace standard treatment and have a positive medico-economic impact, allowing, on the one hand, a reduction of the costs associated with the treatment and the toxicity, and on the other hand, an increase of the patients' quality of life.

Impact of a Process Optimizing the Decision to Continue or Stop Cancer Treatments in Patients With Advanced Non-small Cell Lung Cancer.

We propose to study the optimization of this decision process in an advanced Non-Small-Cell Lung Carcinoma (NSCLC) population, with a Performance Status (PS) ≥ 2 (median survival of approximately 3 months) piloting iteratively (before each decision to continue treatment) a process consisting of an evaluation framework (30 items to be answered by the oncologist with the patient), consolidating: 1. clinical parameters; 2. doctors' expectations regarding the continuation of anticancer treatment; 3. patient expectations and preferences; 4. the possibility of referring the patient to a supportive care specialist and strengthening home care. The process triggers a dialogue between the patient and the oncologist, based on facts and seeks objectivity, ultimately allowing a shared decision. In this prospective comparative study, the rate of systemic oncological treatment during the last month of life will be measured consecutively, over a period of usual management, followed by a period of systematic application of a process of optimization of the medical decision.

Prospective Non-interventional Study of Adult Patients With Acute Myeloid Leukemia (AML)

During the last fifteen years, the landscape of AML diagnosis and therapeutical options has markedly evolved. Refined genetic and prognostic characterizations, together with new drug approvals and new allogeneic hematopoietic stem cell transplantation (HSCT) procedures, have increased patient journey diversity. I - At initial AML diagnosis, not all newly diagnosed patients are entering clinical trials. A substantial proportion of them are treated with standard therapies outside of any trial. To date, the standard approved frontline treatment options include: 1. Standard intensive 3+7 (anthracycline + cytarabine) chemotherapy ± an approved FLT3 inhibitor (midostaurine, Rydapt®), according to different dose schedules in older versus younger patients 2. Combination of sequential gemtuzumab ozogamicin (GO, Mylotarg®) with 3+7 3. Liposomal formulation of daunorubicin + cytarabine (CPX-351, Vyxeos®) 4. Less intensive chemotherapy with azacytidine or low dose cytarabine (LDAC) in patients considered as not eligible for the more intensive options above The investigator's choice is guided by AML and patient's characteristics, and by the approved indications for each of these treatment options. This study will thus start including these specific options. Further study amendments might be necessary in case of new standard treatment definition. II - Secondly, no specific salvage regimen has emerged as a standard in patients with primary refractory or relapsed AML (R/R AML). R/R AML is thus an important field for investigational new drugs (INDs) and precision medicine development. To date, the only IND approved to treat R/R AML is gilteritinib for FLT3-mutated AML patients. The French agency ANSM also allow to use GO for treating R/R AML patients in the frame of a RTU (Recommendation Temporaire d'Utilisation). In the "real life", because of the multiplicity of treatments used in these patients, some of them being now quite efficient, it has become difficult to accurately describe the general outcome of R/R AML patients. III - Thirdly, allogeneic HSCT is no more considered at the ultimate and final goal of AML therapy in all patients, as it was in the past. Transplant indications have been better described and HSCT in now evaluated in the context of the whole treatment course, including pre- and post-transplant therapy, as well as pre- and post-transplant minimal residual disease (MRD) levels. For all these reasons, it is of utmost importance to document the various characteristics, treatments and outcomes of patients treated in the real-life, outside of clinical trials, for 1) real-world treatment evaluation; 2) post-approval use of recently approved drugs; 3) standardization and improvement of routine patient management; and 4) better disease understanding.