Clinical Applicability of Liquid Biopsy in Chondrosarcoma
ConditionChondrosarcoma of the Bone
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-99
SponsorMedical University of Graz
About this trial
Treatment of intermediate (i.e. atypical cartilaginous tumour, ACT) and malignant cartilaginous tumours (i.e. chondrosarcoma) involves surgical resection, while effects of systemic therapies are limited. Thus, it is of importance to diagnose these tumours timely, estimate their prognosis, and detect recurrences at early stages. Apart from diagnosis and disease monitoring with cost-intensive, as well as ionizing radiation-exposing imaging modalities, liquid biopsy constitutes a potent, non-invasive diagnostic, prognostic and predictive tool in oncology. Intermediate/malignant cartilaginous neoplasms are known to frequently harbour specific mutations, as Isocitrate dehydrogenase 1/2 (IDH1/2). These may well be detectable with liquid biopsy, a non-invasive diagnostic measure. Further, other genetic alterations found in primary tumour tissue as well as cytokines/chemokines may be of additive diagnostic and prognostic value.
This prospective cohort study aims at answering 4 questions: 1) Possibility to differentiate between ACT and higher-grade chondrosarcoma by measuring mutant IDH1/2 circulating free DNA (cfDNA) in blood stream; 2) Feasibility to detect recurrences during follow-up by monitoring mutant IDH1/2 cfDNA; 3) Prognostic potential of high mutant IDH1/2 cfDNA levels; 4) Additive diagnostic/prognostic value of other genetic alterations found in primary tumour tissue as well as cytokine profiling.
Over 2 years, an estimated 60 patients with intermediate/malignant cartilaginous tumours will meet the inclusion criteria. At 11 time points (preoperatively, postoperatively, after 6 weeks, as well as 3, 6, 9, 12, 15, 18, 21 and 24 months), blood samples will be ascertained. The following methodological steps will be carried out: 1) next generation sequencing of primary tumour tissue towards IDH1/2 mutations (and further genetic alterations); 2) selection of digital droplet polymerase chain reaction (ddPCR) assays with patient-specific probes; 3) blood sample collection; 4) cfDNA extraction from blood samples; 5) Quantification of mutant IDH1/2 cfDNA with ddPCR; 6) cytokine and chemokine profiling in blood samples. Patients will be followed-up for 2 years, resulting in an overall study period of 4 years.
This study may help to elucidate the role of liquid biopsy in diagnosis and follow-up of patients with chondrosarcoma.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Semimalignant or malignant cartilaginous tumour (atypical cartilaginous tumour, chondrosarcoma G1/2/3, dedifferentiated chondrosarcoma)
Definite surgery of primary tumour
Disqualifiers
Prior tumour-specific treatment (except for biopsy)
Trial population
Adult patients (age 18 - 99 years) diagnosed with semimalignant (atypical cartilaginous tumour) or malignant (chondrosarcoma G1/2/3, dedifferentiated chondrosarcoma) cartilaginous neoplasm undergoing surgery at a single tertiary sarcoma centre.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
laboratory biomarker analysis
Diagnostic testLaboratory biomarker analysis at several pre-defined time points during follow-up.
Molecular pathology
Other interventionTesting of primary tumour tissue with next generation sequencing towards presence of IDH and other mutations.
Treatment groups
60 Participants
are divided into 1 treatment groupGroup A: Patient cohort2 interventions
Trial outcomes
Primary outcomes
1
NGS analysis of primary tumour tissue
Analysis of primary tumour tissue with next generation sequencing for presence of IDH and other mutations
Time frame
Up to 12 weeks following biopsy/definite surgery2
Digital droplet PCR
Analyse blood samples obtained ad pre-defined time points during follow-up with digital droplet PCR towards presence of patient-specific mutations.
Time frame
From 1 week prior to biopsy/surgery up to 24 months after biopsy/surgery (or in case of development of recurrent disease, up to 24 months following recurrence).Secondary outcomes
1
Immune profiling
Carry out immune profiling (i.e. next generation sequencing \[NGS\]-based proteomics of cytokines/chemokines) using blood samples obtained ad pre-defined time points during follow-up.
Time frame
From 1 week prior to biopsy/surgery up to 24 months after biopsy/surgery (or in case of development of recurrent disease, up to 24 months following recurrence).Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov