Clinical trial NCT05529615: Circulating Tumor DNA Guided Adjuvant Chemotherapy for Colon Cancer
Official title: Circulating Tumor DNA Guided Adjuvant Chemotherapy for Colon Cancer: A Prospective, Multicenter, Open-label, Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Colon Cancer
Circulating Tumor DNA
Keywords: chemotherapy
ctDNA
colon cancer
prognosis
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
First posted: 2022-09-07
Enrollment: 2684
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The IDEA study classified stage III colon cancer into low-risk (T1-3/N1) and high-risk patients (T4 or N2) according to TNM stage. The results showed that for some low-risk patients, chemotherapy could be reduced without survival loss.

In recent years, circulating tumor DNA had achieved encouraging results in monitoring recurrence and metastasis after surgery, and has potential clinical application value. Postoperative ctDNA is also considered as a marker of increased risk of recurrence for stage I-III colon cancer and can provide predictive information for decision making on adjuvant treatment.

The results of GERCOR-PRODIGE, concomitant study of IDEA-FRANCE, showed that in the high-risk group, the patients with ctDNA positive and receiving adjuvant chemotherapy for 6 months had similar prognosis as the patients with ctDNA negative and receiving chemotherapy for 3 months; in the low-risk group, the patients with ctDNA positive but receiving chemotherapy for 3 months had worst prognosis, and the prognosis of patients with ctDNA negative chemotherapy for 3 months and 6 months and ctDNA positive chemotherapy for 6 months were similar. This indicates that risk stratification can be further performed according to the results of ctDNA after clinical pathological staging. Pathological staging is still an important decision-making factor for chemotherapy. It is not reliable to the chemotherapy decision making just based on ctDNA and abandoning clinical staging.

Therefore, a prospective, multicenter, open-label, randomized controlled clinical trial was designed aimed to investigate circulating tumor DNA guided adjuvant chemotherapy for colon cancer. In this study, all the patients are divided into high-risk group and low-risk group according to the postoperative pathology. Patients in each group were randomized to different treatment schedule according to the results of ctDNA.


Eligibility criteria: Inclusion Criteria:

1. Age: 18 to 75
2. Colon adenocarcinoma confirmed by pathology (including high and high differentiated tubular adenocarcinoma, papillary adenocarcinoma, low differentiated adenocarcinoma, mucinous adenocarcinoma and signet ring cell carcinoma)
3. Postoperative pathology is stage II with high-risk factors or stage III;

   High risk stage II refers to stage II colon cancer with at least one of the following:

   a) T4 stage; b) The number of lymph nodes detected was less than 12; c) Poor differentiation (except MSI-H); d) Complicated with LVI or PNI；e) Complicated with obstruction or perforation.
4. No distant metastasis was found in preoperative imaging examination and operation;
5. ECOG score: 0-2 points;
6. MSS/pMMR and BRAF wild type
7. Start time of chemotherapy is less than 2 months from the operation
8. Have sufficient organ functions;
9. The baseline blood routine and biochemical indexes of the subject meet the following standards:

   * hemoglobin ≥ 9.0 g / dl;
   * absolute neutrophil count (ANC) ≥ 1500 / mm3;
   * platelet count ≥ 100000 / mm3;
   * total bilirubin ≤ 1.5 times the upper limit of normal value (ULN);
   * glutamic pyruvic transaminase and glutamic oxalic transaminase ≤ 2.5 times ULN;
   * creatinine ≤ 1.5 times ULN;
10. Patients or family members who can understand the study protocol and are willing to participate in the study shall provide written informed consent.

Exclusion Criteria:

1. Receive chemotherapy, radiotherapy or immunotherapy before operation
2. History of malignant tumor in the past 5 years (except fully cured cervical carcinoma in situ or basal cell carcinoma or squamous epithelial cell skin cancer)
3. Pregnant women
4. Serious mental illness
5. Those with poor physical condition and difficult to complete chemotherapy
6. Patients or family members cannot understand the conditions and objectives of this study

Primary outcomes:
measure: 3-year disease-free survival rate
timeFrame: 3 year
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking university cancer hospital
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Aiwen Wu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: