Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Herbal and Botanical

All Drugs and Chemicals

Cola

Anna Martling, Professor

In clinical practice, there are currently no biomarkers that can guide colorectal cancer treatment in the primary and curative setting. Improved biomarker-based adjuvant treatments would be of greatest value in order to reduce the risk of relapse. There are reasons to believe that measurements of circulating tumor DNA (ctDNA) in plasma could be used to monitor minimal residual disease after surgery. To address this question, a pilot study was conducted with the purpose to demonstrate the feasibility to perform prospective profiling of ctDNA in a cohort of patients with colorectal cancer stage I-III using the already created Nordic infrastructure for clinical research built up for the ALASCCA trial. If the pilot study proves successful, a large randomised controlled Nordic multicenter study is planned where patients with positive ctDNA 4-6 weeks after radical surgery will be randomised to chemotherapy and/or a biologic agent.

Participants will be asked to donate 30ml blood before surgery (baseline), after surgery at 4-6 weeks, 3-, 6-, 12- and 24 months postoperatively to measure cell-free DNA (cfDNA) in plasma.

All biospecimens will be shipped to the biobank at Karolinska Institutet for further processing. DNA will be extracted from tumor tissue and whole blood. Targeted sequencing of tumor tissue and germline DNA will be performed using in solution hybridization-based capture at Clinical Genomics, SciLife Lab, Stockholm. Blood in the CITCCA pilot will be profiled prospectively with a two-week turnover, using the ProBio infrastructure, mimicking a real clinical scenario where minimal residual disease (MRD) information will be available in a condense report format.

Circulating Tumour DNA (ctDNA) as a Prognostic and Predictive Marker in Colorectal Cancer - a Pilot Study

A Pilot Study Investigating the Feasibility to Perform Prospective Circulating Tumor DNA (ctDNA) Profiling in Patients With Colorectal Cancer

Anna Martling

Professor, Senior Consultant Surgeon

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Cystadenocarcinoma, Serous

Cystadenocarcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Neoplasms, Cystic, Mucinous, and Serous

Ovarian Cancer

Ovarian Epithelial Cancer

Adenocarcinoma of the Appendix

Antineoplastic Agents

Carboplatin

high-grade serous ovarian cancer patients (FIGO stages III and IV) with ascites, for whom neoadjuvant chemotherapy is recommended.

Patients will receive neoadjuvant chemotherapy according to ESGO guidelines

Borut Kobal, MD; PhD

Katarina Černe, MD, PhD

Ovarian cancer has the highest mortality rate among all gynecologic cancers, with most patients presenting with advanced stage tumors. About a third of patients do not respond to primary platinum-based chemotherapy treatment, and over time up to 80 % of others develop chemoresistance, rendering recurrent disease incurable. Despite all the studies published in the literature, it has not been proven that the number of cells with expressed ATP7A in certain tumors increases independently of the therapy. In addition, no study has been conducted on a sample of patients with confirmed serous histology of ovarian cancer only. The aim of the study is to demonstrate increased expression of the ATP7A transporter in cells resistant to carboplatin.

RATIONALE:

Recent studies suggest that the copper efflux transporters ATP7A plays an important role in platinum resistance. Despite all the studies published in the literature, it has not been proven that the number of cells with expressed ATP7A in certain tumors increases independently of the therapy. In addition, no study has been conducted on a sample of patients with confirmed serous histology of ovarian cancer only. The literature concludes that new methods are required to detect resistant tumor cells at an early chemotherapy stage and suitably adapt treatment. There is still much uncertainty regarding how the fate of platinum compounds in a cell follows the regulatory copper pathways, especially during transport from the cell. The question is also to what extent these processes are cell-specific, especially because experiments to date regarding the role of ATP7A in resistance to platinum compounds have been conducted on nonserous cell lines (especially of the endometrioid histological type).

AIM OF THE STUDY:

Study will evaluate the ATP7A transporter as an important mediator of chemoresistance to platinum compounds to obtain an additional criterion for the optimal treatment strategy for serous ovarian cancer patients. The focus will primarily be on intrinsic chemoresistance, which determines the initial response to chemotherapy. Research to date has failed to evaluate the influence of ATP7A transporter expression solely on serous ovarian cancer.

The study will demonstrate increased expression of the ATP7A transporter in cells resistant to carboplatin. Because the measurement of ATP7A in bodily fluids is unreliable, the plan is to measure ceruloplasmin in the patients' ascites. Ceruloplasmin is the main copper-transporting protein in the blood. It is synthesized in the cell and, according to findings in the literature, it is ATP7A that is responsible for delivering copper to ceruloplasmin. When copper binds to ceruloplasmin, there is no other way for it to cross the plasma membrane than via the ATP7A transporter. By measuring the ceruloplasmin level in the ascites, ATP7A activity or its localization on the plasma membrane could indirectly be measured as well. To confirm the suitable measurement of ceruloplasmin in the ascites, its values in the patients' blood plasma and tissue will be measured.

METHODS:prospective clinical trial It will include 30 high-grade serous ovarian cancer patients (FIGO stages III and IV) with ascites. The patients will be presented to the gynecological-oncological consultation team at the Ljubljana Division of Gynecology and Obstetrics. Patients for whom neoadjuvant chemotherapy is recommended will be included in the trial.

STATISTICAL ANALYSES: The normality of numerical variables' distribution will be tested with the Shapiro-Wilk test. Relevant parametric tests (Student's t-test) or nonparametric tests (the two-tailed Mann-Whitney U-test) will be used to compare groups.

Role of the ATP7A Transporter in Ovarian Cancer

ATP7A Transporter as Biomarker for Predicting Chemoresistance of Serous Ovarian Cancer

To measure concentration of ceruloplasmin in blood and ascites

To measure concentration of ceruloplasmin after three to six chemotherapy cycles

To measure expresion of ATP7A after three-six cycles of chemotherapy

University of Ljubljana, Faculty of Medicine, Institute of Pharmacology and Experimental Toxicology

University Medical Centre Ljubljana

Asist. David Lukanovic, MD

Esophageal Neoplasms

Head and Neck Neoplasms

Esophageal Diseases

Esophageal Cancer

Docetaxel

Fluorouracil

Cisplatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

5 FU 1000mg/m2; days 1-5; 3 cycles: q21

Cisplatin 80mg/m2; day 1; 3 cycles: q21

5-Fluoruracil, Cisplatinum

Daniela Kandioler, Prof., MBA

Johannes Zacherl, Prof.

Michael Hejna, Prof.

Study Hypothesis:

PANCHO is a prospective randomized, predictive marker study, evaluating the interaction between the potential predictive marker 'p53 genotype' and response to induction chemotherapy in patients with esophageal cancer considered resectable.

170 patients with measurable disease will be enrolled in this study. After testing the marker genotype (two genotypes: p53 normal or p53 mutant) patients will be stratified according to histological subtype only (adeno- or squamous cell carcinoma) and will be randomly assigned to receive 3 cycles of either 5-fluorouracil (5FU)/cisplatin or docetaxel monotherapy as neoadjuvant therapy. All patients will be rendered to subsequent surgery in order to assess both clinical and pathohistological response.

PANCHO will test the hypothesis that p53 genotype is predictive for response to chemotherapy. The study uses the marker by treatment interaction design. In this design, we assume that the status of the marker splits the whole population into two distinct groups (p53 normal versus p53 mutant).

Patients in each marker group are randomly assigned to two different treatments, and planned statistical analysis is to test whether one treatment is superior to the other within each marker group separately.

The marker information but not the treatment is blinded to the patient and the investigators.

p53-Adjusted Neoadjuvant Chemotherapy for Potentially Resectable Esophageal Cancer

p53-Adjusted Neoadjuvant Chemotherapy for Potentially Resectable Esophageal Cancer: A Multicenter, Randomized Controlled, Predictive Marker Clinical Trial

Medical University of Vienna

Austrian Society Of Surgical Oncology

Daniela Kandioler

Univ. Prof. Dr., MBA

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Circulating Tumour DNA (ctDNA) as a Prognostic and Predictive Marker in Colorectal Cancer - a Pilot Study	NCT04726800	Colorectal Canc...		18 Years - 80 Years	Karolinska Institutet
Role of the ATP7A Transporter in Ovarian Cancer	NCT05490407	Gynecologic Can... Ovarian Cancer High Grade Sero... Chemotherapy Ef...	Carboplatin	18 Years - 80 Years	University Medical Centre Ljubljana
p53-Adjusted Neoadjuvant Chemotherapy for Potentially Resectable Esophageal Cancer	NCT00525200	Esophageal Canc...	5-Fluoruracil, ... Docetaxel	18 Years -	Medical University of Vienna

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