Circulating tumor DNA: Where are we now? A mini review of the literature

Table 1 Current active and completed phase II-III clinical trials utilizing liquid biopsy technology

Study title	Cancer type	Phase	Clinical aspect being investigated	Fluid analyzed	Target(s) and study objectives	Identifier
TAGRISSO (Osimertinib) in NSCLC patients in whom T790 mutations are detected by liquid biopsy using BALF, plasma or pleural effusion	Lung cancer (NSCLC)	Phase II	Therapeutic guidance	BALF, plasma or pleural effusion.	EGFR T790M detection	NCT03394118
Post-surgical liquid biopsy-guided treatment of stage III and high-risk stage II colon cancer patients: The PEGASUS trial	Colon cancer	Phase II	Therapeutic guidance	Plasma	ctDNA detection	NCT04259944
Liquid biopsy as a tool to evaluate resistance to first and third lines (AZD9291) (EGFR) (TKIs) in EGFR mutant NSCLC	Lung cancer (NSCLC)	Phase II	Clonal evolution – disease monitoring/therapy resistance	Plasma	EGFR, T790M, C797S, L858R, del 19 EGFR, KRAS/NRAS, BRAF, PI3K	NCT02771314
Liquid biopsy in monitoring the neoadjuvant chemotherapy and operation in gastric cancer	Gastric cancer	Phase II	Disease monitoring/progression/future directed therapy development	Plasma	Compare CTC, ctDNA and ctDNA detection to tumor markers level (CEA, CA 19-9 and CA72-4) and imaging findings to assess post-surgical prognosis	NCT03957564
Clinical utility of liquid biopsy in brigatinib ALK+ patients (CUBIK)	Lung cancer (NSCLC)	Phase II	Disease monitoring/clonal evolution.	Plasma	EML4-ALK rearrangement detection	NCT04223596
Olmutinib trial in T790M (+) NSCLC patients detected by liquid biopsy using BALF extracellular vesicular DNA	Lung cancer (NSCLC)	Phase II	Therapeutic guidance- treatment	BALF	EGFR T790M detection	NCT03228277
Nalirinox neo-pancreas RAS mut ctDNA study	Pancreatic cancer	Phase II	Disease monitoring/clonal evolution.	Plasma	KRAS detection	NCT04010552
Mechanisms of resistance in EGFR mutated nonpretreated advanced lung cancer receiving OSimErtib (MELROSE)	Lung cancer (NSCLC)	Phase II	Disease monitoring/clonal evolution/mechanisms of resistance	Plasma	EGFR T790M detection	NCT03865511
PRIMUS002: Looking at 2 neo-adjuvant treatment regimens for resectable and borderline resectable pancreatic cancer (PRIMUS002)	Pancreatic cancer	Phase II	Therapy response	Plasma	Liquid biopsy analyzed using ctDNA at different time-points to see if these can be used to define patient subgroups	NCT04176952
Intermittent or continuous panitumumab plus FOLFIRI for RAS/B-RAF wild-type metastatic colorectal cancer (IMPROVE)	Colon cancer	Phase II	Disease monitoring/clonal evolution/mechanisms of resistance	Plasma	RAS and BRAF detection	NCT04425239
Osimertinib treatment on EGFR T790M plasma positive NSCLC patients (APPLE)	Lung cancer (NSCLC)	Phase II	Disease monitoring/progression	Plasma	EGFR T790M detection	NCT02856893
Treatment of metastatic bladder cancer at the time of biochemical relapse following radical cystectomy (TOMBOLA)	Bladder cancer	Phase II	Disease monitoring/prognosis	Plasma	ctDNA levels to assess metastatic disease	NCT04138628
Deferred cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma: The NORDIC-SUN-Trial (NORDIC-SUN)	Renal cell carcinoma	Phase III	Future translational research	Plasma	ctDNA quantity and NGS to establish mutations.	NCT03977571
Study of the molecular features of postmenopausal women with HR+ HER2-negative aBC on first-line treatment with ribociclib and letrozole and, in patients with a PIK3CA mutation, on second-line treatment with alpelisib plus fulvestrant (BioItaLEE)	Breast cancer	Phase III	Disease progression/clonal evolution/therapy response	Plasma	PIK3CA detection	NCT03439046
Second-line FOLFIRI + panitumumab in subjects with wild type RAS metastatic colorectal (BEYOND)	Colorectal cancer	Phase II	Disease progression/clonal evolution	Plasma	RAS/BRAF detection	NCT03751176

NSCLC: Non-small cell lung cancers; BALF: Bronchoalveolar lavage fluid; EGFR: Epidermal growth factor receptor; TKIs: Tyrosine kinase inhibitors; ctDNA: Circulating tumor DNA; CEA: Carcinoembryonic antigen; CTC: Circulating tumor cells; NGS: Next-generation sequencing.