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

Not Applicable

Active, not recruiting

• Conditions: Digestive System Disease; Gastro-Intestinal Disorder; Gastrointestinal Cancer; Rectal Neoplasms; Rectal Cancer; ctDNA; Colorectal Neoplasms; Colonic Diseases; Rectal Diseases; Colorectal Cancer
• Interventions: Diagnostic Test: ctDNA-analysis; Other: Intensified Follow-up Schedule

• Registration Number: NCT04084249
• Lead Sponsor: Claus Lindbjerg Andersen

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-09-04
• Study First Submitted QC: 2019-09-06
• Study First Posted: 2019-09-10
• Study Start: 2020-01-01
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-04
• Last Update Posted: 2024-07-09
• Primary Completion: 2028-06-30
• Study Completion: 2028-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 359

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

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ctDNA guided surveillance	ctDNA-analysis	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.
ctDNA guided surveillance	Intensified Follow-up Schedule	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.

Primary Outcome Measures

Name	Time	Method
FCI	5 years	Fraction of patients with relapse receiving intended curative resection or local treatment aiming at complete tumor destruction as defined at the relevant MDT conference.

Secondary Outcome Measures

Name	Time	Method
TTMR	2 years	Time to molecular recurrence
AR	3 years	Adherence rate for patients following ctDNA-guided and standard of care surveillance
CE	5 years	Cost-effectiveness. QoL/Utility weights for the quality-adjusted life years parameter will be QLU-C10D based on EORTC QLQ-C30.
3yr-OS	3 years	Overall survival at 3 years
TTCR	3 years	Time to clinical recurrence
5yr-OS	5 years	Overall survival at 5 years
FCRI	3 years	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.
QoL	3 years	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.
IES-C	3 years	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.

Trial Locations

Locations (10)

Regional Hospital Horsens; 🇩🇰 Horsens, Central Denmark Region, Denmark

Regional Hospital Randers; 🇩🇰 Randers, Central Denmark Region, Denmark

Herlev Hospital; 🇩🇰 Herlev, Capital Region Of Denmark, Denmark

Gødstrup Hospital; 🇩🇰 Herning, Central Denmark Region, Denmark

Aalborg University Hospital; 🇩🇰 Aalborg, North Denmark Region, Denmark

Zealand University Hospital; 🇩🇰 Køge, Denmark

Regional Hospital Viborg; 🇩🇰 Viborg, Denmark

Odense University Hospital; 🇩🇰 Odense, The Region Of Southern Denmark, Denmark

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Bispebjerg Hospital; 🇩🇰 Copenhagen, Denmark