ctDNA-Based Adjuvant Chemotherapy for High-Risk Rectal Cancer

NCT07188025 | Not Yet Recruiting Phase 3

• 2 other identifiers: NL82006.078.222024-517700-12-00
• Study Type: interventional
• Target: 103
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to investigate whether adjuvant chemotherapy can prevent disease recurrence in patients with high-risk rectal cancer who have detectable ctDNA after surgery. The main research question the REACT study aims to answer is: \- Does adjuvant chemotherapy improve disease-free survival in patients with high-risk rectal cancer with detectable ctDNA after surgery? Interventions: \- Patients with detectable ctDNA after surgery and randomised to the experimental group will be offered adjuvant chemotherapy (4 cycles CAPOX/6 cycles FOLFOX) within 12 weeks after surgery.

Conditions

Rectal Cancer

Keywords

ctDNA; Adjuvant Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Disease-free survival, intention-to-treat

  To investigate whether the disease-free survival in patients with rectal cancer who have detectable ctDNA after primary tumour resection, can be improved by administration of adjuvant chemotherapy.

  Calculated from the date of surgery to the date of progression (recurrence) or death from any cause of the patient, whichever occurs first, assessed up to 2 years of follow-up

Secondary Outcomes (8)

• Overall survival, intention-to-treat

  From the date of surgery to the date of death from any cause of the patient, with a median follow-up of 5 years

• Disease-free survival, per-protocol

  Calculated from the date of surgery to the date of progression (recurrence) or death from any cause of the patient, assessed up to 2 years of follow-up

• Overall survival, per-protocol

  Calculated from the date of surgery to the date of death from any cause of the patient, with a median follow-up of 5 years

• The effect of adjuvant chemotherapy on quality of life - EQ-5D-5L

  Questionnaires are obtained within PLCRC at baseline, 3 months, 6 months, 1 year, 1.5 years, 2 years and yearly after, assessed up to 4 years of follow-up

• The effect of adjuvant chemotherapy on quality of life - QLQ-C30

  Questionnaires are obtained within PLCRC at baseline, 3 months, 6 months, 1 year, 1.5 years, 2 years and yearly after, assessed up to 4 years of follow-up

Other Outcomes (3)

• The proportion of ctDNA-positive patients with specific mutational profiles.

  Assessed from the blood sample taken 14-28 days after rectal surgery.

• Correlations between ctDNA mutational profiles and clinical/pathological parameters and time to recurrence

  Assessed from the blood sample taken 14-28 days after rectal surgery.

• Concordance rate (%) between mutations identified in ctDNA and matched tumour tissue

  Assessed from the blood sample taken 14-28 days after rectal surgery.

Study Arms (2)

Standard of Care

NO INTERVENTION

Control group ctDNA+

Adjuvant chemotherapy

EXPERIMENTAL

Intervention group ctDNA+

Drug: Adjuvant chemotherapy

Interventions

Adjuvant chemotherapy DRUG

Adjuvant chemotherapy consists of 6 cycles of 5FU/folinic acid and oxaliplatin (FOLFOX) every 2 weeks, or 4 cycles of capecitabine and oxaliplatin (CAPOX). Duration of treatment will be 3 months (12 weeks).

Adjuvant chemotherapy

Eligibility Criteria

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

You may qualify if:

• Detectable ctDNA in the postoperative blood sample
• Age ≥ 18 years
• WHO performance score 0-1
• Informed consent for PLCRC with specific consent for additional blood withdrawals and offering of future experimental research
• Informed consent for the REACT trial.
• Histological confirmed rectal cancer; either treated with neoadjuvant (chemo)radiotherapy, and/or clinical/pathological T3/T4 and/or N+ in case no neoadjuvant therapy was administered.
• Eligible to receive treatment with combination adjuvant chemotherapy (CAPOX/FOLFOX) according to the treating physician.
• Mentally competent and able to read and understand Dutch language.

You may not qualify if:

• Metastatic disease
• Another malignancy in previous 5 years, with the exception of treated carcinoma in situ or skin cancer other than melanoma
• Incomplete primary tumour resection (R1 or R2 resection)
• Contra-indication for fluoropyrimidines or oxaliplatin
• Neoadjuvant oxaliplatin based systemic treatment, e.g. treated with the RAPIDO regimen consisting of short course radiotherapy followed by 6 cycles of CAPOX or 9 cycles of FOLFOX prior to surgery
• Patients with a clinical complete response, who will not undergo surgery.
• Pregnant and lactating women
• History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance of the intervention group
• Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator
• Serious infections (uncontrolled or requiring treatment)
• Current or recent (within 28 days prior to randomisation) treatment with another investigational drug or participation in another study interfering with the primary endpoint.

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Prospectief Landelijk CRC Cohort (PLCRC): collaborator
• Dutch Colorectal Cancer Group (DCCG): collaborator

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Chemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Cornelis Verhoef, MD, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mirthe Ubink, MD

CONTACT

+31650162308; REACT@erasmusmc.nl

Cornelis Verhoef, MD, PhD

CONTACT

0031 10 704 1902

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: The proposed study is conducted within the prospective Dutch ColoRectal Cancer (PLCRC) cohort and follows the trial within cohort (TwiCs) design, i.e. a randomised controlled trial within a prospective cohort

Study Record Dates

• First Submitted: September 3, 2025
• First Posted: September 23, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2035
• Last Updated: September 23, 2025

Record last verified: 2025-09