Clinical trial NCT03038217: Investigation of the Value of ctDNA in Diagnosis, Treatment, and Surveillance of Surgically Resectable Colorectal Cancer
Official title: Investigation of the Value of ctDNA Analysis in the Diagnosis, Treatment, and Surveillance of Patients With Surgically Resectable Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Rectal Cancer, Adenocarcinoma
Neoadjuvant Chemoradiation
Keywords: rectal cancer
neoajuvant chemoradiation
circulating tumor DNA
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Geneplus-Beijing Co. Ltd.
First posted: 2017-01-31
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In this study, we aim to investigate the value of circulating tumor DNA (ctDNA) analysis in the diagnosis, treatment, and surveillance of patients with surgically resectable colorectal cancer, by performing serial analysis of ctDNA, next-generation sequencing of surgical specimens, and observation of patients undergoing radical resection of the tumor with or without adjuvant chemo- and/or radiotherapy.

Detailed description: A prospective, observational study to determine the value of circulating tumor DNA (ctDNA) for predicting the therapeutic effects of the combined modality treatment for colorectal cancer and the patients' long-term prognosis.

Research objects: patients with surgically resectable colorectal cancer. After giving fully informed consent, the prospective participants will undergo the classical combined modality treatment according to NCCN guidelines. Serial analysis of ctDNA will be performed at specific time points including pre-treatment, (post-NCRT for NCRT patients), postoperative week 1, post-ACT, postoperative year 1, 2, and 3. The next-generation sequencing of surgical specimens will be performed as well. Participants will be observed and examined during the entire course of treatment and the follow-up period. The 3 year disease free survival (3y-DFS) will be the primary end-point.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 18 to 75 years old.
2. Patients with surgically resectable colorectal cancer, while without distal metastasis of the disease.
3. Patients with ASA physical status scroe of I to III.
4. Patients who can fully understand the content of the informed consent form and sign it upon their own opinions.
5. Patients who can coordinate with the researchers to undergo the long-term post-treatment rechecks and follow-ups.

Exclusion Criteria:

1. Patient has any underlying or current medical condition, which, in the opinion of the Investigator, would interfere with the evaluation of the patient (e.g., end-stage liver disease, pulmonary hypertension, systemic lupus erythematosis etc.).
2. Patient is pregnant or lactating.
3. Patient has a history of malignancy within 5 years except curatively treated basal cell carcinoma, squamous cell carcinoma in a non-mucosal, ultraviolet exposed area, or cervical carcinoma.
4. Patient is participating in any other clinical trials within 30 days prior to screening.
5. Patient has severe mental illness.
6. Patient has any other conditions, which, in the opinion of the Investigator, would interfere with the evaluation of the subject.

Primary outcomes:
measure: 5y DFS
timeFrame: 5 years
measure: 5y LR
timeFrame: 5 years
measure: 5y OS
timeFrame: 5 years
Secondary outcomes:
measure: Changes of ctDNA level after surgery
timeFrame: 1 month
measure: Changes of ctDNA level after adjuvant therapy
timeFrame: 6 months
measure: Changes of ctDNA level when disease recurs
timeFrame: 5 year
Other outcomes:
Locations:
Study officials:
References:
citation: Reinert T, Scholer LV, Thomsen R, Tobiasen H, Vang S, Nordentoft I, Lamy P, Kannerup AS, Mortensen FV, Stribolt K, Hamilton-Dutoit S, Nielsen HJ, Laurberg S, Pallisgaard N, Pedersen JS, Orntoft TF, Andersen CL. Analysis of circulating tumour DNA to monitor disease burden following colorectal cancer surgery. Gut. 2016 Apr;65(4):625-34. doi: 10.1136/gutjnl-2014-308859. Epub 2015 Feb 4.
citation: Stroun M, Anker P, Maurice P, Lyautey J, Lederrey C, Beljanski M. Neoplastic characteristics of the DNA found in the plasma of cancer patients. Oncology. 1989;46(5):318-22. doi: 10.1159/000226740.
citation: Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, Silliman N, Tacey M, Wong HL, Christie M, Kosmider S, Skinner I, Wong R, Steel M, Tran B, Desai J, Jones I, Haydon A, Hayes T, Price TJ, Strausberg RL, Diaz LA Jr, Papadopoulos N, Kinzler KW, Vogelstein B, Gibbs P. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016 Jul 6;8(346):346ra92. doi: 10.1126/scitranslmed.aaf6219.
citation: Zhou J, Chang L, Guan Y, Yang L, Xia X, Cui L, Yi X, Lin G. Application of Circulating Tumor DNA as a Non-Invasive Tool for Monitoring the Progression of Colorectal Cancer. PLoS One. 2016 Jul 26;11(7):e0159708. doi: 10.1371/journal.pone.0159708. eCollection 2016.