LIQUID BIOPSY FOCUSING ON CIRCULATING TUMOR CELLS AND CIRCULATING TUMOR DNA AS PRECISION MEDICINE IN GASTROINTESTINAL TUMORS

Active, not recruiting

• Conditions: Cancer of Rectum; Cancer of Pancreas; Cancer of Stomach

• Registration Number: NCT06940778
• Lead Sponsor: Hospital do Coracao

Brief Summary

This is a prospective, observational, multicenter cohort study. Our main objective is to to evaluate the use of CTCs and ctDNA with prognostic factors in locally advanced rectal tumors treated with total neoadjuvant therapy (TNT), recently adopted as clinical practice, and to analyze the functionality of CTCs and ctDNA in the follow-up of locally advanced and metastatic pancreatic and gastric tumors.

Secondary objectives:

* To verify the influence of CTC and ctDNA kinetics on the response to treatment of the three tumors;

* To correlate RAD23B/TYMS findings and CTC kinetics with DFS in locally advanced rectal tumors;

* To correlate HER-2 and PDL-1 expression in CTCs in gastric cancer with progression-free and overall survival;

* To verify the correlation between EGFR methylation in ctDNA of metastatic gastric tumors and PFS and OS;

* Correlate KRAS mutations in ctDNA in locally advanced pancreatic and rectal cancer with progression-free and overall survival;

* Compare the mutational profile of the primary tumor with that of the main components of the liquid biopsy (CTCs and ctDNA), in the three disease scenarios.

Detailed Description

To evaluate CTCs we will isolate cells from blood of patients by ISET method (Rarecells, France). The DNA from CTCs will be evaluated by digital PCR (Qiagen). Also, the ctDNA. Patients will be evaluated three times ( before the beginning of therapy, 6 and 12 months later. The study will be only observational. Patients will be followed by clinical and images exams.

Study Timeline

• Study Start: 2025-01-10
• Status Verified: 2025-04
• Study First Submitted: 2025-04-07
• Study First Submitted QC: 2025-04-15
• Study First Posted: 2025-04-23
• Last Update Submitted: 2025-04-24
• Last Update Posted: 2025-04-27
• Primary Completion: 2026-06-10
• Study Completion: 2026-12-10

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 273

Inclusion Criteria

Inclusion criteria:

• Age ≥ 18 years;

For locally advanced rectal cancer:

• Patients with histological confirmation of adenocarcinoma of the distal rectum who are candidates for sphincter preservation and undergoing TNT, a long-course CRT regimen, followed by CT (5-FU + consolidation oxaliplatin);
• Tumors with a location that requires rectal amputation, except for very early tumors (cT1N0);
• Absence of distant metastases (M0).

For locally advanced or metastatic stomach cancer:

• Patients with histological confirmation of adenocarcinoma of the stomach or esophagogastric junction (EGJ) (cT2-4, cN0-3, M0-1) who have not undergone any previous treatment for the disease, surgical or systemic;

• Patients who will undergo the following treatments:

  1. (T2 to T4, N+ and M0): 4 cycles of FLOT, surgery, + 4 cycles of FLOT (5-Fluorouracil, Oxaliplatin and Docetaxel);
  2. Initial cases: T2 to T4 N0: Surgery followed by adjuvant chemotherapy: CAPOX (capecitabine + oxaliplatin) or FOLFOX (5-Fluorouracil + capecitabine) - 8 cycles;
  3. Initially unresectable T4N3: If PDL1+ and CPS > 5: CT (FOLFOX or XELOX) + nivolumab. If HER-2 + XELOX or FOLOFX + transtuzumab - after 8 cycles evaluate resectability;
  4. Metastatic disease: if HER2 negative - XELOX or FOLFOX with Nivolumab or pembrolizumab. If HER2 positive XELOX or FOLFOX with trastuzumab + pembrolizumab.

For localized or metastatic pancreatic cancer:

• Patients with histologically confirmed pancreatic adenocarcinoma (cT1-4, N0-2, M0-1) who have not undergone any prior surgical or systemic treatment for the disease.

• Patients who will undergo the following treatments:

  1. T1 to T3, N0 to N2 - resectable: Surgery followed by 12 cycles of FOLFIRINOX (oxaliplatin, 5-fluorouracil and irinotecan)
  2. Borderline resectable: Neoadjuvant chemotherapy with FOLFIRINOX for 8 cycles and surgery
  3. Unresectable disease - locally advanced: FOLFIRINOX for 12 cycles or Gemcitabine + nanoparticle paclitaxel for 8 cycles

Exclusion Criteria

• Mid-rectum tumors or tumors with microsatellite instability.
• Stomach tumors or early EGJ (cT1N0)
• Patients who have undergone prior treatment or any surgical intervention in the last 30 days.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
disease free survival	from baseline (day 1) until the date of first documented progression , assessed up to 24months	from the diagnosis of advanced disease to disease progression

Secondary Outcome Measures

Name	Time	Method
overall survival	from the day one until the date of death from any cause, assessed up to 30 months	from the diagnosis of advanced or metastatic disease to death

Trial Locations

Locations (1)

Hcor; 🇧🇷 São Paulo, SP, Brazil