Circulating Tumor DNA Based Decision for Adjuvant Treatment in Colon Cancer Stage II-III

NCT07821333 | Active Not Recruiting Phase 2

• 1 other identifier: CIRCULATE-SPAIN-01
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 7

Brief Summary

This trial has been designed to prove the feasibility of using liquid biopsy detection of minimal residual disease (MRD) to guide the postsurgical clinical management of early colon cancer patients. Moreover, it is important to define if conventional (CAPOX) versus intensive (FOLFOXIRI) adjuvant chemotherapy could convert plasma ctDNA positive into a ctDNA negative status.

Conditions

Minimal Residual Disease; Circulating Tumor Cell; Colorectal Neoplasms Malignant

Outcome Measures

Primary Outcomes (2)

• Proportion of patients with ctDNA clearance following FOLFOXIRI treatment

  Proportion of patients with detectable circulating tumor DNA (ctDNA) prior to treatment who become ctDNA-negative following intensive adjuvant treatment with FOLFOXIRI.

  Prior to treatment initiation, immediately after adjuvant chemotherapy completion, and every 4 months for 2 years (phase IIa).

• Difference in ctDNA clearance rate between FOLFOXIRI and CAPOX(FOLFOXIRI) versus conventional adjuvant therapy (CAPOX).

  Proportion of patients with detectable circulating tumor DNA (ctDNA) prior to treatment who become ctDNA-negative following adjuvant chemotherapy, compared between the intensive treatment group (FOLFOXIRI) and the standard-of-care group (CAPOX).

  Prior to treatment initiation, immediately after adjuvant chemotherapy completion, and every 4 months for 2 years (phase IIb).

Secondary Outcomes (5)

• Disease-free survival in patients with positive ctDNA

  At 24 months after the end of treatment (phase IIb).

• Disease-free survival according to ctDNA clearance status

  At 12 months after the end of treatment (phase IIb).

• Treatment-related toxicity of FOLFOXIRI compared with CAPOX

  During the treatment period and immediately after adjuvant chemotherapy completion (phase IIb).

• Quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

  At baseline, 3 months after treatment initiation, and immediately after adjuvant chemotherapy completion (phase IIb).

• Quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29)

  At baseline, 3 months after treatment initiation, and immediately after adjuvant chemotherapy completion (phase IIb).

Study Arms (2)

FOLFOXIRI

EXPERIMENTAL

FOLFOXIRI intensive adjuvant chemotherapy

Drug: FOLFOXIRI

CAPOX

ACTIVE COMPARATOR

CAPOX standard adjuvant chemotherapy

Drug: CAPOX

Interventions

FOLFOXIRI DRUG

Patients will receive 12 cycles each 14 days

Also known as: intensive adjuvant chemotherapy

FOLFOXIRI

CAPOX DRUG

Patients will receive 8 cycles each 21 days

Also known as: standard adjuvant chemotherapy

CAPOX

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• CIRCULATE-SPAIN-01 trial written informed consent.
• Age ≥ 18 years and ≤ 75 years.
• Histologically confirmed diagnosis of operable stage II or stage III Colon Cancer.
• Postoperative, ctDNA positive.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Normal organ functions, as follows:
• Absolute neutrophil count (ANC) ≥ 1500/μL.
• Platelets ≥ 100.000/μL.
• Hemoglobin ≥ 9.0 g/dL OR ≥ 5.6 mmol/L.
• Total bilirubin ≤ 1.5 x upper level of normality (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 x ULN.
• Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) ≤ 2.5 x ULN.
• Note: Synchronous primary tumours are accepted. Note: Patients with rectal cancer above the peritoneal reflection, who have not undergone postoperative chemotherapy or radiotherapy and who have risk factors, may be included in the trial.

You may not qualify if:

• Patients having a MicroSatellite Instability High (MSI-H) or MisMatch Repair Deficient (MMRd) tumor are excluded from the study (done according to standard clinical practice).
• History of another neoplastic disease, unless in remission for ≥ 5 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Had an incomplete diagnostic colonoscopy and/or polyps' removal for patients in whom the remaining colon was not removed or explored. Note: Patients with intraoperative complete colonoscopy or early perioperative complete colonoscopy and/or patients with incomplete colonoscopy, but who do have a CT Colono or Intraoperative Colonoscopy, may be eligible to be recruited in the study.
• Macroscopic or microscopic evidence of residual tumor (R1 or R2 resections). Patients should never have had any evidence of metastatic disease (including presence of tumor cells in the peritoneal lavage).
• Current treatment with another investigational drug or participation in another investigational study.
• Patient unable to comply with the study protocol owing to psychological, social or geographical reasons.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
• Inadequate contraception (male or female patients) if of childbearing or procreational potential.
• Current clinically unresolved cardiovascular disease.
• Acute or subacute intestinal occlusion or history of inflammatory bowel disease.
• Pre-existing neuropathy \> grade 1. Known grade 3 or 4 allergic reaction to any of the components of the treatment.
• Has a known DihydroPyrimidine Dehydrogenase (DPD) deficiency.
• Has a known Gilbert Syndrome or UGT1A1 homozygous \*28/\*28 germline variant.
• Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required.
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus infection. Note: no testing for Hepatitis B and Hepatitis C is required.

Sponsors & Collaborators

• Fundación para la Investigación del Hospital Clínico de Valencia: lead

Study Sites (7)

Hospital Universitario de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitari Vall D'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, 14004, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

MeSH Terms

Conditions

Colonic Neoplasms; Neoplasm, Residual; Neoplastic Cells, Circulating

Interventions

FOLFOXIRI protocol

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis

Study Officials

• Andrés Cervantes Ruipérez, MD

  Hospital Clínico Universitario de Valencia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single to double arm transition study in which patients are firstly enrolled into a single arm (Phase IIa) study expandable to a randomized double arm (Phase IIb). In the first stage (Phase IIa) the success of the experimental treatment (FOLFOXIRI) is compared to a fixed value. If the pre-fixed result is achieved, the trial will be expanded to a phase IIb in which patients will be enrolled to randomly receive experimental treatment (FOLFOXIRI) or control (CAPOX).

Study Record Dates

• First Submitted: July 23, 2021
• First Posted: September 15, 2026
• Study Start: January 1, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: September 15, 2026

Record last verified: 2026-09

Locations

ES (7)