Clinical Research Directory

Interest of Circulating Tumor DNA in Digestive and Gynecologic/Breast Cancer

Circulating tumor DNA (ctDNA) offers the possibility of accessing the tumor genome from circulating blood through a simple blood test. It is currently used for diagnostic, prognostic and predictive purposes of response or resistance to oncological treatments. These advances in ctDNA have been made possible by major developments in molecular biology techniques in recent years, as the detection of ctDNA requires very sensitive techniques such as Next Generation Sequencing (NGS). CtDNA overcomes this problem of very limiting tumor heterogeneity during a solid biopsy. All of these applications make circulating DNA an increasingly essential tool in the management of cancer patients. The studies are currently in most cases on small numbers and are retrospective. In addition, exosomes are also a biomarker of the future that can also be detected in the bloodstream . Exosomes are nanovesicles 50 to 200 nm in diameter released into the extracellular environment via the endosomal pathway by fusion with the plasma membrane. They are very informative since they transport tumor genetic material in the form of DNA, mRNA and miRNA, but also adhesion proteins, immunostimulatory molecules and cytoskeleton, enzymes and Heats shock proteins ( HSP). The aim of the ADIGYN study is to set up a large prospective cohort to assess the diagnostic, prognostic and predictive impact of ctDNA and exosomes in digestive and gynecological / breast cancers. From the circulating DNA, we characterize the ActDNA on the molecular level thanks to the study of different point mutations usually used but also of new described mutations having a therapeutic impact and the search for other genetic alterations having an impact on the therapeutic strategy (such as microsatellite instability) or the study of exosomes and their composition. To assess resistance to oncological treatments, ctDNA will be analyzed at the start of treatment, during treatment, during progression and / or relapse and also during monitoring or treatment break

Using ctDNA to Determine Therapies for Lung Cancer

This is a study to look at whether the presence of circulating tumour DNA (ctDNA) in the blood can help to predict whether giving adjuvant treatment after surgery can decrease the chance of the cancer coming back in people with lung cancer.

Atezolizumab + Sacituzumab Govitecan to Prevent Recurrence in TNBC (ASPRIA)

The purpose of this study is to determine if a combination of two drugs sacituzumab govitecan and atezolizumab works as a treatment for residual cancer in the breast or lymph nodes and have circulating tumor DNA in the blood. This research study involves the following investigational drugs: * Sacituzumab govitecan * Atezolizumab

ctDNA in CRC Patients Undergoing Curative-intent Surgery for Liver Metastases

This is a prospective multicenter cohort study, was designed to explore the prognostic value of ctDNA as a biomarker of disease response and recurrence or death in patients undergoing curative-intent surgical resection of Colorectal cancer liver metastasis.

Circulating Tumor DNA Based Adjuvant Chemotherapy in Stage II Colon Cancer Patients: the MEDOCC-CrEATE Trial

Patients in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) with non-metastatic colon cancer that gave consent for additional blood withdrawals are enrolled in the observational PLCRC-MEDOCC substudy. In this study, blood is collected before surgery, after surgery and during follow-up. Within PLCRC-MEDOCC, patients with stage II colon cancer that are not considered to have an indication for adjuvant chemotherapy, can be included in the MEDOCC-CrEATE subcohort under the condition that they gave informed consent in PLCRC for biobanking of tissue and for future studies (Trial within Cohorts design). Patients included in MEDOCC-CrEATE will be randomized 1:1 to the (A) ctDNA-based treatment group versus (B) the standard of care group. A total of 1320 patients will be randomized. Patients randomized to the ctDNA-based treatment group will have their post-surgery samples analysed directly after informed consent for MEDOCC-CrEATE. All patients with detectable ctDNA will be offered adjuvant chemotherapy (3 months CAPOX). Patients with undetectable ctDNA will receive routine follow-up at the surgical department. The aim of this Trial within Cohorts study is to investigate how many patients with detectable ctDNA after surgery start with adjuvant chemotherapy.

Circulating Tumor DNA-guided Neoadjuvant Treatment Strategy for Locally Advanced Rectal Cancer

Rectal cancer still remains one of the most popular tumors, however, distance metastasis still remains as high as 30% and the long-term survival outcomes are still unsatisfying. The recent conception of total neoadjuvant therapy and immune therapy is becoming popular and the oncologic effects are encouraging, especially in terms of circulating tumor DNA (ctDNA), the prognostic value of ctDNA has been demonstrated by our prior study. This study will carry out accurate ctDNA-guided neoadjuvant therapy on the basis of previous studies of the research group, and give appropriate treatment plans and treatment intensity to patients with different disease degrees. At the same time, combined with the latest progress in clinical diagnosis and treatment, the potential beneficiaries of immunotherapy were screened scientifically, and the combined immunotherapy was implemented accordingly.

CtDNA as a Novel Biomarker of Treatment Efficacy in Patients With Ovarian Cancer

This study is a prospective observational clinical trial. Patients who were diagnosed and treated for the first time were enrolled and their surgical pathology was confirmed to be high-grade serous ovarian cancer. At the same time, these patients will receive first-line maintenance treatment with PARP inhibitors after traditional chemotherapy. During the trial period, patients' plasma will be collected before surgery, after chemotherapy, during targeted maintenance therapy, and during disease progression, and ctDNA-specific genomes will be detected, and clinical data will be collected over the same period. It is expected that specific ctDNA can be used to predict the efficacy of PARP inhibitors in patients with ovarian cancer, and to detect the recurrence of the disease early.

NSCLC Liquid Biopsies and Exhaled VOC

The objective of the study is to determine the feasibility of recruiting participants and using sputum, Bronchoalveolar lavage (BAL) and exhaled Volatile Organic Compounds (VOC) in addition to blood, as biological samples for detecting mutations in extracted cell-free DNA in non-small cell lung cancer (NSCLC) patients, before and after surgery, and any recurrence within a 24-month postoperative follow-up period. This is a pilot feasibility study, proposed as a 24-month prospective, single-center, non-interventional, observational trial with NSCLC-adenocarcinoma patients indicated for resection surgery with curative intent.

Exploring the Mechanism of Primary Resistance to Third-generation EGFR-TKIs as First-line Treatment in EGFR-positive Advanced NSCLC (PRECISE Study)

Lung cancer is currently the world's largest malignant tumor for cancer-related deaths with non-small cell lung cancer (NSCLC) accounting for 80%-85%. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), especially the 3rd-generation EGFR-TKIs have demonstrated strong antitumor effects in EGFR-positive patients. However, approximately 20% of EGFR-positive were primarily resistant to 3rd generation EGFR-TKIs, i.e., clinical non-response or disease progression in the short term. This study aimed to clarify the molecular indicators that predict the benefits of 3-rd EGFR-TKIs as first-line therapy in NSCLCpatients with EGFR-positive. Further, to clarify their primary drug resistance mechanisms, which is of great significance for the treatment and clinical decision-making of NSCLC disease.

Danish Vulva Cancer Recurrence Study

The overall aim is to investigate different aspects of recurrence detection in women with vulva cancer (VC) to identify optimal treatment- and surveillance programs. DaVulvaRec is a Danish nationwide multicenter study with patient inclusion from Aarhus University Hospital and Rigshospitalet, Denmark. Applying a mixed method research design, the investigators will collect and analyze patient-reported outcome measures in combination with procedural data to evaluate symptomatology and map actions taken during the patient's pathway from primary disease to recurrence. Furthermore, the investigators aim to examine if circulating tumor-DNA (ctDNA) can be detected in liquid biopsies from VC patients. All patients will be followed for two years or until recurrence. Patient-reported outcome measures will be completed every four months during surveillance, and liquid biopsies will be collected prospectively for later analyses. Total number of patients to be included is 295 according to a power calculation. All patients in the clinical study will be included in the intervention group, while data on a historical control group will be obtained from The Danish Gynecological Cancer Database. Hence, the control group will consist of 1000 VC patients diagnosed between 2011-2022. Hypotheses: * All patients with VC will have specific tumor markers in the primary tumor that will be detectable in liquid biopsies as ctDNA at the time of diagnosis. * Measurement of ctDNA after primary treatment and during surveillance will allow detection of residual disease, improve allocation for adjuvant treatment, and will allow early detection of recurrent VC. * Proactive use of repeated PROM assessments in combination with procedural actions during surveillance will allow early detection of recurrent VC and early identification of late effects after treatment.

Clinical Application of ctDNA Dynamic Monitoring in Neoadjuvant Therapy for HER2-positive Breast Cancer Patients

1. To explore the predictive value of ctDNA in HER2 positive breast cancer neoadjuvant therapy population; 2. To evaluate the prognostic value of ctDNA in HER2 positive breast cancer neoadjuvant therapy population.

Circulating Tumor DNA Guided Adjuvant Chemotherapy for Colon Cancer

The IDEA study classified stage III colon cancer into low-risk (T1-3/N1) and high-risk patients (T4 or N2) according to TNM stage. The results showed that for some low-risk patients, chemotherapy could be reduced without survival loss. In recent years, circulating tumor DNA had achieved encouraging results in monitoring recurrence and metastasis after surgery, and has potential clinical application value. Postoperative ctDNA is also considered as a marker of increased risk of recurrence for stage I-III colon cancer and can provide predictive information for decision making on adjuvant treatment. The results of GERCOR-PRODIGE, concomitant study of IDEA-FRANCE, showed that in the high-risk group, the patients with ctDNA positive and receiving adjuvant chemotherapy for 6 months had similar prognosis as the patients with ctDNA negative and receiving chemotherapy for 3 months; in the low-risk group, the patients with ctDNA positive but receiving chemotherapy for 3 months had worst prognosis, and the prognosis of patients with ctDNA negative chemotherapy for 3 months and 6 months and ctDNA positive chemotherapy for 6 months were similar. This indicates that risk stratification can be further performed according to the results of ctDNA after clinical pathological staging. Pathological staging is still an important decision-making factor for chemotherapy. It is not reliable to the chemotherapy decision making just based on ctDNA and abandoning clinical staging. Therefore, a prospective, multicenter, open-label, randomized controlled clinical trial was designed aimed to investigate circulating tumor DNA guided adjuvant chemotherapy for colon cancer. In this study, all the patients are divided into high-risk group and low-risk group according to the postoperative pathology. Patients in each group were randomized to different treatment schedule according to the results of ctDNA.