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Active, not recruitingNCT04084249Updated Apr 29, 2026

ctDNA-guided Surveillance for Stage III CRC, a Randomized Intervention Trial

An interventional study of ctDNA-analysis and Intensified Follow-up Schedule in Colorectal Cancer, Colo-rectal Cancer and ctDNA, sponsored by Claus Lindbjerg Andersen. Active, not recruiting at 10 sites in Denmark. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-29.

Sponsored by Claus Lindbjerg Andersen · Not applicable, Interventional, and Diagnostic

Phase
Not applicable
Study type
Interventional
Enrollment
359
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

IMPROVE-IT2 is a randomized multicenter trial comparing the outcomes of ctDNA guided post-operative surveillance and standard-of-care CT-scan surveillance. The hypothesis of this study is that ctDNA guided post-operative surveillance combining ctDNA and radiological assessments could result in earlier detection of recurrent disease and identify more patients eligible for curative treatment.

02

Conditions studied

  • Colorectal Cancer
  • Colo-rectal Cancer
  • ctDNA
  • Gastro-Intestinal Disorder
  • Colorectal Neoplasms
  • Gastrointestinal Cancer
  • Gastrointestinal Neoplasms
  • Digestive System Disease
  • Digestive System Neoplasm
  • Colonic Diseases
  • Colonic Neoplasms
  • Colonic Cancer
  • Rectal Diseases
  • Rectal Neoplasms
  • Rectal Cancer
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Colon or rectal cancer, tumor stage III (pT1-4N1-2,cM0) or stage II high-risk (pT4N0,cM0 and pT3N0, cM0 with risk factors)
  • Have received curative intend resection and be candidates for adjuvant chemotherapy

Exclusion criteria

Exclusion Criteria:

  • Not treated with adjuvant chemotherapy
  • Synchronous colorectal and non-colorectal cancer diagnosed per-operative (except skin cancer other than melanoma)
  • Other cancers (excluding colorectal cancer or skin cancer other than melanoma) within 3 years from screening
  • Patients who are unlikely to comply with the protocol (e.g. uncooperative attitude), inability to return for subsequent visits) and/or otherwise considered by the Investigator to be unlikely to complete the study.
04

Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
359 participants (actual)

Study arms

  • Experimental
    ctDNA guided surveillance

    ctDNA analysis will be performed every 4 months postoperatively (4, 8, 12, 16, 20 and 24). At time of first positive ctDNA, patients undergo a whole-body FDG-PET/CT-scan for radiological assessment and a colonoscopy. If the initial assessment is without evidence of recurrence, patients will be offered high-intensive radiological surveillance with FDG-PET/CT-scans every 3 months, until recurrence detection or 21 months has passed. At baseline and months 12, 18, 24 and 36 patients complete the QoL questionnaires including EORTC QLQ-C30, fear of cancer recurrence inventory (FCRI), and impact of events scale for cancer (IES-C). At every FDG-PET/CT-scans the patients also complete the questionnaire.

    Diagnostic Test: ctDNA-analysis · Other: Intensified Follow-up Schedule

  • No intervention
    Standard Danish follow-up program

    Patients will undergo surveillance according to current Danish Guidelines with CT-scans at months 12 and 36 postoperative and colonoscopy every 5 year until age 75. Longitudinal blood samples will be collected at same time-points as in the experimental group but not analyzed until end of trial. At baseline and months 12, 18, 24 and 36 patients complete the QoL questionnaires including EORTC QLQ-C30, fear of cancer recurrence inventory (FCRI), and impact of events scale for cancer (IES-C).

Interventions

  • Diagnostic testctDNA-analysis

    Minimally-invasive blood-based analysis of circulating tumor DNA (ctDNA).

  • OtherIntensified Follow-up Schedule

    PET/CT-scans every 3. month

05

What researchers measure

Primary outcomes

  1. FCI

    Fraction of patients with relapse receiving intended curative resection or local treatment aiming at complete tumor destruction as defined at the relevant MDT conference.

    Time frame: 5 years

Secondary outcomes

  1. TTCR

    Time to clinical recurrence

    Time frame: 3 years

  2. 3yr-OS

    Overall survival at 3 years

    Time frame: 3 years

  3. 5yr-OS

    Overall survival at 5 years

    Time frame: 5 years

  4. QoL

    Quality of Life by use of EORTC QLQ-C30, version 3.0. The QoL outcome measure is differences in QLQ-C30 score at 12, 24 and 36 months between the experimental and control arm.

    Time frame: 3 years

  5. CE

    Cost-effectiveness. QoL/Utility weights for the quality-adjusted life years parameter will be QLU-C10D based on EORTC QLQ-C30.

    Time frame: 5 years

  6. AR

    Adherence rate for patients following ctDNA-guided and standard of care surveillance

    Time frame: 3 years

  7. TTMR

    Time to molecular recurrence

    Time frame: 2 years

  8. FCRI

    Fear of Cancer Recurrence Inventory. The FCRI outcome measure is differences in FCRI at 12, 24 and 36 months between the experimental and control arm.

    Time frame: 3 years

  9. IES-C

    Impact of Events Scale Cancer. The IES-C outcome measure is differences in IES-C at 12, 24 and 36 months between the experimental and control arm.

    Time frame: 3 years

06

Study locations

10 sites
  • Herlev Hospital
    Herlev, Capital Region of Denmark 2730, Denmark
  • Gødstrup Hospital
    Herning, Central Jutland 7400, Denmark
  • Regional Hospital Horsens
    Horsens, Central Jutland 8700, Denmark
  • Regional Hospital Randers
    Randers, Central Jutland 8930, Denmark
  • Aalborg University Hospital
    Aalborg, North Denmark 9000, Denmark
  • Odense University Hospital
    Odense, The Region of Southern Denmark 5000, Denmark
  • Aarhus University Hospital
    Aarhus, 8000, Denmark
  • Bispebjerg Hospital
    Copenhagen, 2400, Denmark
  • Zealand University Hospital
    Køge, 4600, Denmark
  • Regional Hospital Viborg
    Viborg, 8800, Denmark
07

References and documents

Publications

  • Nors J, Henriksen TV, Gotschalck KA, Juul T, Sogaard J, Iversen LH, Andersen CL. IMPROVE-IT2: implementing noninvasive circulating tumor DNA analysis to optimize the operative and postoperative treatment for patients with colorectal cancer - intervention trial 2. Study protocol. Acta Oncol. 2020 Mar;59(3):336-341. doi: 10.1080/0284186X.2019.1711170. Epub 2020 Jan 10. No abstract available. PubMed 31920137 ↗

Study documents

  • Study protocol · Jul 3, 2024
  • Statistical analysis plan · Jun 25, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT04084249
Lead sponsor
Claus Lindbjerg Andersen
Collaborators
University of Aarhus
Responsible party
Claus Lindbjerg Andersen (Professor, University of Aarhus) — Sponsor-investigator
First posted
Sep 10, 2019
Start date
Jan 1, 2020
Primary completion
Jun 30, 2028 (estimated)
Completion
Jun 30, 2028 (estimated)
Last update
Apr 29, 2026

Study contacts

Claus L Andersen, PhD
principal investigator · Department of Molecular Medicin, Aarhus University Hospital

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is active, not recruiting, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.

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