Clinical trial NCT06589388: ctDNA Monitoring to Predict the Efficacy of TNT for Rectal Cancer
Official title: ctDNA Monitoring to Predict the Efficacy of Total Neoadjuvant Therapy for Rectal Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Rectal Cancer
Rectal Cancer Stage II
Rectal Cancer Stage III
Keywords: liquid biopsy
circulating tumor DNA
Vietnam
total neoadjuvant therapy
Lead sponsor: Gene Solutions
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population consists of patients aged 18 years and older, diagnosed with stage II-III rectal cancer, and indicated for total neoadjuvant chemotherapy. Participants must meet all inclusion criteria and no exclusion criteria. Recruitment will take place at 175 Military Hospital, Nguyen Tri Phuong Hospital, and 108 Military Center Hospital.

Brief summary: This is a prospective observational study with three primary objectives:

Objective 1: Evaluate the detection rate and changes in circulating tumor DNA (ctDNA) levels in blood samples from colorectal cancer patients before, during, and after total neoadjuvant therapy (TNT).

Determine the detection rate and change of CtDNA in blood samples of cancer patients before, during, and after TNT then assess changes in ctDNA expression within the study population during treatment.

* Determine the ctDNA positivity rate before treatment.
* Determine the ctDNA positivity rate during TNT.
* Determine the ctDNA positivity rate after TNT and assess ctDNA level changes during treatment.

Objective 2: Investigate the relationship between ctDNA expression and MRI/CT scan imaging with the pathological complete response (pCR) to neoadjuvant therapy :

* Correlation between ctDNA detection and pCR/TRG/NAR score. Calculate the Positive Prediction Value - PPV, Negative Prediction Value - NPV of ctDNA,
* Correlation between MRI/CT scan imaging and pCR. Calculate the PPV and NPV of MRI/CT scan
* Combination of ctDNA detection and MRI/CT scan imaging to predict pCR. Calculate the PPV and NPV of the combined markers.

Objective 3: Evaluate the relationship between post-TNT ctDNA expression and disease-free survival in colorectal cancer patients.

Detailed description: This is a prospective observational study conducted at the Medical Genetics Institute (MGI), in collaboration with 3 hospitals (175 Military Hospital, Nguyen Tri Phuong Hospital, and 108 Military Central Hospital). Participants must meet all inclusion criteria and no exclusion criteria (detailed in the eligibility section).

Sample Collection

* 10 mL of peripheral blood (Streck tubes) is collected for ctDNA analysis at 3 time points: pre-TNT (at diagnosis), middle of treatment (after chemoradiotherapy or after chemotherapy), and post-TNT (before surgery).
* 6-8 slides (6um thickness/slide) of FFPE biopsy tumor samples before treatment
* 6-8 slides (6um thickness/slide) of FFPE tumor samples collected after surgery. This sample is used to compare the mutational profiles with the corresponding biopsy samples.

Clinical results for collection

* Age, sex, medical history
* Number, size, and stage (TNM) of tumor
* MRI and/or CT scan images and reports at pre-treatment, mid-treatment, and end-treatment (before surgery)
* Histopathological evaluation of biopsy and surgery tissues, and conclusion of pathological response

  * TNM classification, pCR conclusion
  * TRG conclusion
* Disease-free survival follow-up for 2 years

Eligibility criteria: Inclusion Criteria:

* 18 years and older, both genders
* Patients are diagnosed with stage II-III rectal cancer and indicated for total neoadjuvant therapy
* Biopsy FFPE sample is available at the time of diagnosis
* Patients consented to participate in the study

Exclusion Criteria:

* Stage I rectal cancer, recurrent or metastatic cancer
* Other cancer metastasis to the rectum
* Patients are indicated for chemoradiation therapy only
* Have been or are being treated for cancer
* Patients do not agree to participate in the studies.

Primary outcomes:
measure: To investigate the detection rate and change of ctDNA in blood samples of rectal cancer patients during total neoadjuvant therapy
timeFrame: 12 months
measure: To investigate the relationship between ctDNA expression and MRI/CT scan imaging with pCR response in total neoadjuvant therapy (TNT)
timeFrame: 6 months
measure: Evaluate the relationship between post-TNT ctDNA expression and disease-free survival in colorectal cancer patients in 2 years
timeFrame: 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Ho Chi Minh City
country: Vietnam
facility: Medical Genetics Institute
Study officials:
affiliation: Medical Genetics Institude
name: Sinh D Nguyen, PhD
role: PRINCIPAL_INVESTIGATOR
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