Neoplasms

All Conditions

Symptoms and General Pathology

Rare Diseases

Glioma

Neoplastic Cells, Circulating

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neoplasm Metastasis

Neoplastic Processes

Neuroepithelioma

* Correlate the results of the tissue samples with those of the blood samples, the concentration of ctDNA found, and the magnetic resonance images prior to the biopsies.
* Compare other variables such as time, money, and the impact on the patient (recovery time after biopsies, pain, sequelae,...) between the liquid biopsy procedure and the conventional tissue biopsy procedure.

Analysis of the circulating free DNA in blood patients affected by gliomas

Liquid Biopsy

Coloma Moreno

Silvia Gil, PhD

Silvia Gil

The present pilot study aims to investigate a new strategy in the liquid biopsy protocol for the diagnosis of gliomas based on the detection of circulating tumor DNA in the blood of patients with brain lesions compatible with this type of tumor.

In order to increase the sensitivity of the technique, the investigators will work with raw blood samples through minimally invasive procedures. The subsequent analysis will be done with digital PCR, due to its low detection limit. The mutational results of each patient's samples will be compared with those obtained from the corresponding tissue biopsies. This step will allow the team to determine the robustness and reliability of the liquid biopsy. The grading of the tumor, as well as the confirmation of the diagnosis, will be obtained from the histological data.

With the inclusion of more patients in the future, and with the optimization of the mutations investigated, the investigators want to standardize the protocol for the diagnosis of gliomas with liquid biopsy. This technique is less invasive than current surgical procedures used for diagnosis. In addition, using fewer hospital resources should allow a more accurate and rapid diagnosis of the pathology, and therefore, start the more personalized therapeutic stage earlier.

Currently, brain tumors are detected by means of an imaging technique (usually magnetic resonance imaging) with a contrast agent. The determination of the type of tumor, as well as its grading, is usually done subsequently with a biopsy of the tissue, where different solid samples are extracted as representative as possible to analyze them in the Pathological Anatomy service. Nevertheless, there are some factors that limit surgical access, such as: the advanced age of the patient, the location of the tumor in eloquent or risky areas, as well as the presence of large tumors with very diffuse borders. In these cases, the diagnosis of the brain tumor is usually made directly with the magnetic resonance image, which implies a risk of error due to the lack of clinical information from this test.

Limitations like these make the minimally invasive procedure of liquid biopsy an extremely necessary diagnostic tool. For this reason, the investigators want to start a pilot study of this technique in those patients with brain lesions in the resonance images compatible with a glioma-like tumor.

In particular, the main aim of the study is to analyze the blood samples obtained from these patients in order to detect and quantify the circulating DNA (ctDNA) of tumor cells on it. These DNA fragments are expelled into the bloodstream by mechanisms still unknown as a result of numerous processes of apoptosis and necrosis of tumor cells. By analyzing them through a ddPCR, the investigators will try to detect the specific mutations present in this tumoral ctDNA, allowing the team to confirm the presence of a glioma-type tumor, and providing real-time information of its classification as astrocytoma or oligodendroglioma.

Analysis of Circulating DNA in Blood Samples of Glioma-affected Patients

Pilot Study of Liquid Biopsy as a Diagnostic Tool for Gliomas by Analyzing Circulating Tumor DNA in Blood Samples, and Its Validation With the Corresponding Tissue Biopsies.

Circulating free DNA detection in blood samples of patients by means of a ddPCR

Corporacion Parc Tauli

Principal Investigator

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Cisplatin

Antimetabolites

Patients will be followed with computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological examination at every four months.

Receive two cycles of cisplatin-based adjuvant chemotherapy 50mg/m2 D1 and gemcitabine 1000mg/m2 D1 and D8 at every 21 days. After that, patients will be followed with conduction of computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological examination at every four months.

Two additional cycles of cisplatin-based adjuvant chemotherapy 50mg/m2 D1 and gemcitabine 1000mg/m2 D1 and D8 at every 21 days.

cisplatin, gemcitabine

Follow-up

Michelle S Almeida, PhD

Rachel H Machado, MCS

This study hypothesizes that patients who persist with cell-free human papillomavirus deoxyribonucleic acid (cfHPV-DNA) plasma expression at the end of standard treatment, can derive the benefit of using adjuvant chemotherapy in locally advanced cervical cancer (CC). After standard treatment based on concomitant chemoradiotherapy regime, a qualitative and quantitative research of cfHPV-DNA in plasma of patients will be conducted. Those with a negative qualitative research result will leave the study. Patients who have positive research for plasma 16/18 cfHPV-DNA at the end of chemoradiotherapy treatment will be randomized to receive two additional cycles of adjuvant chemotherapy or observation. Patients will be followed with conduction of computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological examination at every four months.

A prospective, randomized, multicenter, national, superiority, parallel, clinical trial, design to evaluate implementation components for conducting a national clinical trial using adjuvant chemotherapy in patients with locally advanced cervical cancer, selected by cfDNA-HPV biomarker. At the end of this pilot study, reaching feasibility goal, it is proposed to amplify size sample, with the same design.

Patients will be randomized by stratified randomization process to belong to one of the groups: control (Group B) or intervention (Group C), emphasizing homogeneity of risk factors between them. A randomized list will be generated by using a suitable software, using variable size blocks (2 or 4), with stratification for site and staging. The confidentiality of the randomization list will be maintained through an automated, centralized, Internet-based randomization system, available 24 hours a day (RedCap). Selected patients must receive standard treatment based on concomitant chemoradiotherapy regime, with dose of radiation of 40-50 greys (Gy) (considering additional boost of 10-15 Gy in lymph nodes, radiologically or surgically, compromised) and brachytherapy of 30-40 Gy and cisplatin 40mg/m2 weekly. After four weeks of the end of treatment, a qualitative and quantitative research of cfHPV-DNA in plasma of patients will be conducted. Those with a negative qualitative research result will leave the study. Patients who have positive research for plasma 16/18 cfHPV-DNA at the end of chemoradiotherapy treatment will be randomized to receive two additional cycles of adjuvant chemotherapy or observation. Patients will be followed with conduction of computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological examination at every four months.

A prospective, randomized, multicenter, national, superiority, parallel, clinical trial, design to evaluate implementation components for conducting a national clinical trial using adjuvant chemotherapy in patients with locally advanced cervical cancer, selected by cfDNA-HPV biomarker. At the end of this pilot study, reaching feasibility goal, it is proposed to amplify size sample, with the same design. The participants will conduct a blood collection for research of cfDNA-HPV and will receive conventional treatment, gold standard currently, characterizing the descriptive phase of the research. In the second operational phase, it will happen the study randomization, designing an experimental study. The pilot study is scheduled to last one year and estimate the possibility to recruit between 30 and 50 patients during 2023.

Adjuvant Chemotherapy in cfHPV-DNA Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer

Adjuvant Chemotherapy in Cell-free Human Papillomavirus Deoxyribonucleic Acid (cfHPV-DNA) Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer (CC)

Data could be shared after reasonable request of the principal investigator.

Accessing regulatory process, hiring and training of investigator sites.

Analyzing the impact of pandemic on disease diagnosis period.

Potential for recruiting 4 to 12 patients/month in each investigator site is sufficient to reach sample goal.

Validation of operation structure includes repository, data collection tools, logistics for intervention distribution (chemotherapy) to the participating sites, strategies for recruitment and stimulation of adherence to intervention and follow-ups.

Objectify 85% or more of adherence rates during intervention.

Aiming at reaching up to 20% during follow-ups and identification of critical factors for loss of follow-up and suggesting mitigation strategies.

Description of overall rates (non-comparative between treatment groups) of progression-free survival.

Description of overall rates (non-comparative between treatment groups) of overall survival.

Description of response rate via Response Evaluation Criteria In Solid Tumours (RECIST) criteria 1.1 2009.

Description of quality of life via European Organisation for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (QLC-C30) and a complementary module of the cervical cancer-specific Quality of Life module of the European Organization for Research and Treatment of Cancer (EORTC QLQ-CX24).

Description of tolerance to proposed intervention, by creating a Data and Safety Monitoring Board (DSMB).

University of Sao Paulo

Hospital do Coracao

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Multiple Pulmonary Nodules

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

blood sample (2 tubes of 7.5 mL of blood = 15 mL) during the preoperative check-up on the day of the ultrasound-bronchoscopy in order to compare the sensitivity of the analysis of free circulating DNA present in the supernatant of pulmonary nodules less than 20 mm samples taken under ultrasound-bronchoscopy to that present in the plasma

Patients will be taken from an additional blood sample (2 tubes of 7.5 mL of blood = 15 mL) during the preoperative check-up on the day of the ultrasound-bronchoscopy in order to compare the sensitivity of the analysis of free circulating DNA present in the supernatant of pulmonary nodules less than 20 mm samples taken under ultrasound-bronchoscopy to that present in the plasma.

Blood samples

Valentin HELUAIN, MD

Sandra BERNARD, PM

Valentin HELUAIN

Lung cancer screening is based on low dose CT scan (LDCT), a highly sensitive but poorly specific tool.

Complementary specific approaches are thus strongly needed, among which cell-free DNA (cfDNA) genotyping has been proven highly specific but of low sensitivity (25 to 50% for stage I diseases) due to inconstant tumor shed. Tumor biopsy is thus often required and radial endobronchial ultrasound (rEBUS) bronchoscopy is a minimally invasive approach (\<3% complications) but of limited sensitivity in cases of nodules \< 20 mm.

The investigators hypothesized that methylation analysis on cfDNA floating in supernatant derived from rEBUS specimens could improve rEBUS sensitivity

Tumor biopsy is often required to characterize indeterminate nodules. Radial endobronchial ultrasound (rEBUS) bronchoscopy is often used due to a low rate of complications but its sensitivity is limited for small nodules.

The investigators hypothesized that methylation analysis on cfDNA floating in supernatant derived from rEBUS specimens could improve rEBUS sensitivity.

The primary outcome of this pilot, diagnostic validation, monocentric study is the sensitivity of targeted (9 genes panel) methylation analysis on supernatant cfDNA to detect a malignant nodule.

Secondary outcomes include the comparison of supernatant to pathology and plasma cfDNA methylation analysis.

Specificity, negative predictive value (NPV), positive predictive value (PPV) of targeted (9 genes panel) methylation analysis on supernatant cfDNA to detect a malignant nodule will be analyzed.

60 patients planned for a rEBUS bronchoscopy for one, two or three \< 20 mm nodule, without mediastinal or extra thoracic lesions (cT1N0M0) will be included.

The day of the rEBUS bronchoscopy, 2 7.5 mL blood samples are collected. rEBUS samples' supernatant, usually discarded, is saved.

Cell free DNA is extracted from these biological specimens at the Laboratory of Oncological Medical Biology (LBMO) in Toulouse University Cancer Institute and tested for methylation (targeted analysis on 9 genes).

The patients will be followed for one year to obtain a final diagnosis and correlate it with tissue, nodule supernatant and plasma methylation analyses.

Molecular Analysis of Endoscopic Cytology Samples Supernatant in Pulmonary Nodules

Molecular Analysis of Endoscopic Cytology Samples Supernatant in Pulmonary Nodules (Cancer Or Benign Endoscopy) (KOBE)

Promoter methylation rates of the 9 targeted genes in the free circulating DNA of the endoscopic samples supernatant is obtained by quantitative Polymerase Chain Reaction (PCR) of bisulfite-treated DNA fragments from the cytological samples supernatant after DNA concentration and separation by size at the Centre of Cancer Research of Toulouse (CRCT).

These analyses will be performed blinded to the clinical data and the histopathology result of the lung nodule.

Methylation profiles of free circulating DNA from plasma obtained after centrifugation of blood samples will be obtained by the same method as described for analysis of cytopunction's supernatant methylation profile.

These analyses will be performed blinded to the clinical data and the histopathology result of the lung nodule.

University Hospital, Toulouse

Patients with stage IA inoperable peripheral lung tumor will be performed ablation. cfDNA methylation would be monitored at different times(before surgery , after surgery 1month, 3month, and every 3month in the first year and every 6 months in the second ). Meanwhile, post-treatment response will be evaluated and follow up will be carried out according to the standard procedure.

Patients with stage IA operable peripheral lung tumor will be performed surgery. cfDNA methylation would be monitored at different time(before surgery , after surgery 1month, 3month). Post-treatment response will be evaluated and follow up will be carried out according to the standard procedure.

Patients with stage IA inoperable peripheral lung tumor will be performed ablation. cfDNA methylation would be monitored at different times(before surgery , after surgery 1month, 3month, and every 3month in the first year and every 6 months in the second ).

ablation

Patients with stage IA inoperable peripheral lung tumor will be performed ablation. cfDNA methylation would be monitored at different times(before surgery, after surgery 1month, 3month).

surgery

Jiayuan Sun, MD, PhD

The objective is to screen and monitor the efficacy of cfDNA methylation in patients with stage I lung cancer after ablation, to compare the similarities and differences of cfDNA methylation between surgical treatment and ablation in patients with stage I lung cancer, and to look for new indicators to assess the efficacy of ablation therapy and to monitor lung cancer recurrence.

The objective is to screen and monitor the efficacy of cfDNA methylation in patients with stage I lung cancer after ablation, to compare the similarities and differences of cfDNA methylation between surgical treatment and ablation in patients with stage I lung cancer, and to look for new indicators to assess the efficacy of ablation therapy and to monitor lung cancer recurrence.

The main research content is to screen the cfDNA methylation index that can monitor the efficacy of stage I lung cancer ablation and compare the similarities and differences of cfDNA methylation in patients with stage I lung cancer after surgery and ablation.

cfDNA Methylation Assay for Clinical Evaluation of Patients With Stage IA Lung Cancer After Ablation Operation

Screening and monitoring the change of cfDNA methylation index in patients with stage I lung cancer after ablation

Comparing similarities and differences between cfDNA methylation in surgical treatment and ablation of patients with stage I lung cancer

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Analysis of Circulating DNA in Blood Samples of Glioma-affected Patients	NCT05964153	Glioma Circulating Tum...	Liquid Biopsy	18 Years -	Corporacion Parc Tauli
Adjuvant Chemotherapy in cfHPV-DNA Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer	NCT05764044	Cervical Cancer Cervix Cancer Cervix Neoplasm	cisplatin, gemc... Follow-up	18 Years - 70 Years	Hospital do Coracao
Adjuvant Chemotherapy in cfHPV-DNA Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer	NCT05764044	Cervical Cancer Cervix Cancer Cervix Neoplasm	cisplatin, gemc... Follow-up	18 Years - 70 Years	Hospital do Coracao
Molecular Analysis of Endoscopic Cytology Samples Supernatant in Pulmonary Nodules	NCT05306912	Lung Cancer Lung; Node	Blood samples	18 Years -	University Hospital, Toulouse
cfDNA Methylation Assay for Clinical Evaluation of Patients With Stage IA Lung Cancer After Ablation Operation	NCT04413656	Lung Cancer	ablation surgery	18 Years - 85 Years	Shanghai Chest Hospital

Spots Global Cancer Trial Database for circulating free dna