Neoplasms

Digestive System Diseases

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Gastrointestinal Stromal Tumors

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Patients with a proven KIT exon 11 mutated GIST covered by our in-house designed ddPCR assay.

Regular 3-12 monthly follow-up by CT-scan will be compared to results of ctDNA analysis. Blood for analysis of mutation in ctDNA will be collected at the same moment a CT-scan is performed

vena punction

An KL Reyners, MD, PhD

N. Steeghs, MD, PhD

A. K.L. Reyners, MD, PhD

R. Bleckman, MD

A. J Gelderblom, MD, PhD

A J Gelderblom, MD, PhD

I. Desar, MD, PhD

R HJ Mathijssen, MD, PhD

An observational, multicenter study will be performed. Regular 3-12 monthly follow-up by CT-scan will be compared to results of ctDNA analysis. Blood for analysis of mutation in ctDNA will be collected at the same moment a CT-scan is performed. All samples will be analyzed at the reference Pathology laboratory at the UMCG. A part of the samples will also be analyzed in other institutions to implement the ddPCR. Primary endpoint is concordance between CT-scan and ctDNA analysis results, from which the negative predictive value (NPV) of our ddPCR assay will be calculated.

This is an observational, non-interventional, multicenter study. The study will be performed within the Dutch GIST consortium (NKI-AvL, Erasmus MC, Radboud UMC, LUMC and UMCG). Patients diagnosed with GIST with a KIT exon 11 mutations that can be detected by our ddPCR assay are eligible. In this way we will study a homogenous patient population with GIST that (usually) responds very well to initial TKI treatment. Therefore, the KIT mutation status must be known. Patients can enter the study at any time point of their disease trajectory. Patients included in GALLOP-11 will have follow-up as described in the European Society of Medical Oncology and Dutch guidelines but with blood draws for ctDNA assessment at similar time points.

The primary objective is the negative predictive value (NPV) of the ddPCR assay result in relation to the results of the CT-scan and/or MRI scan (according to RECIST 1.1) at the same time point. Concordance of these results will be determined, from which the negative predictive value (NPV) of our ddPCR assay will be calculated. This is considered the most important value, as the most harmful scenario would be to miss progressive disease because not seen on ctDNA while it could have been seen on CT (and/or MRI). That would mean that ctDNA analysis is not reliable enough to replace CT-scan (and/or MRI) follow-up in the future.

To determine the negative predictive value, at least 250 patients need to have an evaluable follow-up strategy. To pursue a solid follow-up period within an achievable timeline, patients with at least four ctDNA measurements, accompanied by a CT-scan (and/or MRI scan), will be considered evaluable for the NPV analysis. Patients who have progression within four scans are always evaluable, since a positive outcome outweighs negative outcomes because it is known that ctDNA should have had measured change once it is seen on CT-scans (and/or MRI scans).

The GALLOP-11 Study

Validation of Mutation Analysis in Circulating Tumor DNA With a ddPCR Assay as Diagnostic and Follow-up Tool for Patients With a KIT Exon 11 Mutated GIST: GALLOP-11

The negative predictive value of the ddPCR assay with regard to KIT exon 11 circulating tumour mutation digital droplet PCR (ddPCR) assay in relation to CT-scans.

To establish the sensitivity and specificity of the designed KIT exon 11 mutation ddPCR assay

The detection of ctDNA expressed in copies/mL and fractional abundance, assessed by the designed KIT exon 11 circulating tumour mutation digital droplet PCR (ddPCR) assay, in different laboratories, and by Agena Bioscience, will be assessed.

The first detection of increase in the level of the primary KIT exon 11 mutation in ctDNA determined in time to progression seen on standard radiological evaluation by CT-scan based on RECIST 1.1

Based on mutation analysis of tumor biopsies of patients with progressive disease, ctDNA assays will be designed and tested

Based on progression of disease on CT, we will analyze ctDNA of patients to determine wether secondary mutations could be found before radiologic progression

Dutch Cancer Society

University Medical Center Groningen

Coordinating investigator/project leader

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Testicular Neoplasms

Endocrine Gland Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Male Urogenital Diseases

Endocrine System Diseases

Testicular Diseases

Gonadal Disorders

Patients who developed cardiovascular disease after testicular cancer treatment

A random selection out of the total cohort of testicular cancer patients per participating hospital

Vena punction

J. A. Gietema, MD, PhD

Testicular cancer (TC) is a rare disease, which mostly affects young men aged 15-35 years. Their life expectancy has greatly improved due to the introduction of platinum-containing chemotherapy for disseminated TC in the late 1970s. Given the good prognosis of TC nowadays, prevention or early detection of late adverse effects of TC treatment has become increasingly important. Current literature suggests that TC treatment, and specifically exposure to platinum agents, is associated with increased risk of cardiovascular morbidity and mortality. The precise role of treatment components like platinum in the pathogenesis of cardiometabolic changes and cardiovascular disease (CVD) warrants further investigation, since it is not known if CVD develops through direct platinum-induced damage of the vascular wall or by mediation through development of cardiometabolic riskfactors. The aim of this study is to identify risk factors for development for CVD after treatment for TC. A more profound insight into pathophysiologic mechanisms and identification of risk factors for CVDs is needed to facilitate development of preventive strategies and to optimize survivorship care.

Design: The investigators will perform a multicenter case-cohort study. Patients treated for TC who developed cardiac disease ((either myocardial infarction, proven coronary artery disease (grade ≥2) or congestive heart failure (grade ≥2)) will be invited by their (former) treating oncologist to participate in this study (cases). Furthermore, in each hospital a random sample of 15% of the total population treated for TC will be invited (the subcohort). The investigators will collect detailed diagnostic- and treatment data on TC and on (risk factors for) CVD for all cases as well as for all subcohort members. All cases and subcohort members will be approached to complete a questionnaire and to donate a blood sample for DNA analysis, after written informed consent. Patients who were younger than 40 years at TC diagnosis and younger than 75 years at moment of study contact will be asked to participate in the cardiometabolic risk inventory sub study. For this, participants have to undergo a basic study assessment consisting of physical examination, venapuncture and handing in a morning urine sample. This assessment can be performed at the participating hospital, their general practitioner or during a home visit by a member of the investigators research team. Additional (non-invasive) cardiovascular function measurements (IMT and AGEs) are only performed in the UMCG.

Blood samples: analysis of cardiovascular risk factors (lipid profile, glucose metabolism, hormonal status), platinum levels and several biomarkers.

Urine samples: microalbuminuria, platinum levels. DNA: polymorphisms in candidate genes for development of cardiovascular damage, leukocyte telomere length

TACkLE Study - Tackling Adverse Chemotherapy-associated Late Effects

A Case-cohort Study to Identify Risk Factors for Cardiovascular Disease in Testicular Cancer Survivors

To evaluate the independent and joint effects of disease- and treatment characteristics of TC patients on cardiovascular disease risk.

To evaluate the effect of cardiometabolic risk factors (presence of metabolic syndrome, smoking behaviour, obesity, hypertension, dyslipidemia, diabetes mellitus, family history, physical activity) on cardiovascular disease risk in TC patients.

To determine endothelial activation, hemostatic activity and inflammatory activity (represented by circulating biochemical markers) years after treatment for TC and its relationship between development of (components of) the metabolic syndrome and development of cardiovascular diseases.

To evaluate the presence of hypogonadism in TC survivors and to investigate the association between hypogonadism and presence of (components of) the metabolic syndrome and development of cardiovascular disease.

To investigate the presence of candidate single nucleotide polymorphisms in genomic DNA and telomere length and its association with presence of (components of) the metabolic syndrome and development of cardiovascular disease.

To investigate the impact of cardiovascular disease on Quality of Life (QoL) in TC survivors.

In patients treated with platinum-containing chemotherapy: to evaluate circulating platinum levels in TC survivors and to investigate the relationship between circulating platinum levels and presence of (components of) the metabolic syndrome and development of cardiovascular disease.

Patients visiting the UMCG for the study visit: to evaluate thickness of the intima media of the carotid artery as a marker for subclinical damage in TC survivors, and to investigate the relationship between abnormal intima media thickness and presence of (components of) the metabolic syndrome and development of cardiovascular disease.

Patients visiting the UMCG for the study visit: to assess the elasticity of the arterial wall of the carotid artery in TC survivors, and to investigate the relationship between abnormal arterial stiffness and presence of (components of) the metabolic syndrome and development of cardiovascular disease.

Patients visiting the UMCG for the study visit: to assess levels of AGEs with help of the SAF in TC survivors and to to investigate the relationship between SAF and presence of (components of) the metabolic syndrome and development of cardiovascular disease.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The GALLOP-11 Study	NCT05178030	Gastro-intestin...	vena punction	18 Years -	University Medical Center Groningen
TACkLE Study - Tackling Adverse Chemotherapy-associated Late Effects	NCT02276430	Testicular Canc...	Vena punction	18 Years - 75 Years	University Medical Center Groningen
TACkLE Study - Tackling Adverse Chemotherapy-associated Late Effects	NCT02276430	Testicular Canc...	Vena punction	18 Years - 75 Years	University Medical Center Groningen

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