Clinical trial NCT05633342: Project CADENCE (CAncer Detected Early caN be CurEd)
Official title: Development and Validation of a Blood Test for Screening and Early Detection of Multiple Cancers Based on Circulating Cell-free Nucleic Acid Profiles - Project CADENCE (CAncer Detected Early caN be CurEd)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Thoracic Cancer
Ovarian Cancer
Liver Cancer
Prostate Cancer
Gastric Cancer
Colorectal Cancer
Breast Cancer
Esophageal Cancer
Pancreatic Cancer
Keywords: MCED
Diagnostic Tests
MiRNA
CfDNA
CtDNA
Lead sponsor: MiRXES Pte Ltd
Sponsor class: INDUSTRY
First posted: 2022-12-01
Enrollment: 15000
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will be carried out in 4 phases, namely Phase 1A, 1B, 1C, and 1D. Phase 1A and 1B will be carried out in parallel. Upon the completion of Phase 1A and 1B, Phase 1C will be initiated, followed by Phase 1D, which is the final phase of this study.

All four phases involve participant recruitment (except Phase 1A), sample and data collection, and sample data analysis. Subjects recruited for CADENCE will be divided into four groups: (1) Healthy average-risk (2) Increased-risk (3) High-risk and (4) Malignant.

Brief summary: With existing evidence showing the difference in miRNA expression levels between non-cancer and cancer groups, the investigators assume that levels of DNA methylation, RNA expression as well as protein concentration will also be dysregulated during disease progression. Combining the power of multi-omic cancer biomarkers, the investigators hypothesize that the sensitivity and specificity of MiRXES MCST can be significantly improved compared to existing multi-cancer diagnostic tests.

In this study, the investigators propose to develop and validate blood-based, multi-cancer screening tests through a multi-omics approach.

Detailed description: This study consists of four (4) objectives:

* Characterize intra-cellular multi-omic profiles of cancer and adjacent normal tissues to aid the selection of circulating cancer biomarkers.
* Select and verify circulating multi-omic cancer biomarkers by characterizing the circulating multi-omic profiles of the peripheral blood of cancer patients, high-risk, increased-risk, and healthy controls, guided by tissue-based cancer omics profiles.
* Develop multi-cancer screening in vitro diagnostic assay(s) based on the selected blood-borne circulating multi-omic cancer biomarker panel(s) and build algorithm(s) to distinguish cancer cases from control groups.
* Clinically validate the performance (AUC, sensitivity, specificity) of the multi-cancer screening assay(s) and algorithm(s)

Eligibility criteria: Inclusion Criteria:

Healthy average-risk cohort Individuals representing the general population who self-declare to have no cancer history and have no indications suggestive of underlying cancer development. Subjects will be recruited from a state-of-the-art population study.

Increased-risk (genetic/familial) cohort Individuals carrying certain germline mutations that predispose the subjects to an increased risk of having cancer than the general population. Subjects will be recruited from Cancer Genetics Service (CGS).

High-risk cohort Individuals diagnosed with diseases that have a high risk of progressing to cancer.

Malignant cohort Individuals diagnosed with cancer. Wherever possible, samples for the 'Malignant group' should have a representation of each cancer stage.

Exclusion Criteria:

Pregnant or lactating (self-declaration), unwilling or unable to provide signed informed consent and has or had received chemotherapy or radiotherapy for cancer treatment and/or any other cancer-related treatment.

Primary outcomes:
measure: To discover novel intracellular RNA and methylated DNA cancer biomarkers in fresh frozen tumor tissues.
timeFrame: through study completion, an average of 2.5 years
measure: To select the best-performing multi-omic single-cancer, biomarker panels for each of the cancer types, and develop the corresponding Single-Cancer Early detection Algorithms (SCEAs).
timeFrame: through study completion, an average of 2.5 years
measure: To discover and validate novel cell-free RNA and methylated cell-free DNA cancer biomarkers in the peripheral blood of cancer patients.
timeFrame: through study completion, an average of 2.5 years
measure: To develop the best-performing multi-omic multi-cancer biomarker panel by integration and/or optimization of single-cancer panels and develop the corresponding Multi-Cancer Early detection Algorithm (MCEA).
timeFrame: through study completion, an average of 2.5 years
measure: To develop in vitro diagnostic assay(s) for the Multi-Cancer Screening Test (MCST) and if appropriate Single-Cancer Screening Tests (SCSTs).
timeFrame: through study completion, an average of 2.5 years
measure: To evaluate the clinical performance (AUC, sensitivity, specificity, tissue of origin) of the MCST and if appropriate SCSTs to discriminate cancer cases from control groups.
timeFrame: through study completion, an average of 2.5 years
Secondary outcomes:
measure: Secondary outcome: • To explore the relationship between MCST/SCSTs with clinical outcomes based on the collection of longitudinal follow-up information from medical records.
timeFrame: through study completion, an average of 2.5 years
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Biopollis, Helios
Study officials:
affiliation: MiRXES Pte Ltd
name: Cheng He, PhD
role: STUDY_DIRECTOR
References: