Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer - Intervention Trial 2 (IMPROVE-IT2)

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ClinicalTrials.gov Identifier: NCT04084249

Recruitment Status : Recruiting

First Posted : September 10, 2019

Last Update Posted : June 22, 2022

See Contacts and Locations

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

University of Aarhus

Information provided by (Responsible Party):

Claus Lindbjerg Andersen, Aarhus University Hospital

Tracking Information

First Submitted Date ^ICMJE

September 4, 2019

First Posted Date ^ICMJE

September 10, 2019

Last Update Posted Date

June 22, 2022

Actual Study Start Date ^ICMJE

January 1, 2020

Estimated Primary Completion Date

March 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

FCI [ Time Frame: 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.

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Current Secondary Outcome Measures ^ICMJE

3yr-OS [ Time Frame: 3 years ]
Overall survival at 3 years
5yr-OS [ Time Frame: 5 years ]
Overall survival at 5 years
TTCR [ Time Frame: 3 years ]
Time to clinical recurrence
TTMR [ Time Frame: 2 years ]
Time to molecular recurrence
QoL [ Time Frame: 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.
FCRI [ Time Frame: 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.
IES-C [ Time Frame: 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.
CE [ Time Frame: 5 years ]
Cost-effectiveness. QoL/Utility weights for the quality-adjusted life years parameter will be QLU-C10D based on EORTC QLQ-C30.

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer - Intervention Trial 2

Official Title ^ICMJE

Implementing Non-invasive Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer - Intervention Trial 2

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 Provided

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Not Applicable

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic

Condition ^ICMJE

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

Intervention ^ICMJE

Diagnostic Test: ctDNA-analysis
Minimally-invasive blood-based analysis of circulating tumor DNA (ctDNA).
Other: Intensified Follow-up Schedule
PET/CT-scans every 3. month

Study Arms ^ICMJE

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 months 4, 12, 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 FCRI questionnaire.
Interventions:
- 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 months 4, 12, 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).

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

254

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date ^ICMJE

March 31, 2028

Estimated Primary Completion Date

March 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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.

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: Claus L Andersen, PhD	+45 78455319	cla@clin.au.dk
Contact: Kaare A Gotschalck, PhD	+45 78423786	kaarsune@rm.dk

Listed Location Countries ^ICMJE

Denmark

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT04084249

Other Study ID Numbers ^ICMJE

IMPROVE-IT2

Has Data Monitoring Committee

Not Provided

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Plan to Share IPD:

Current Responsible Party

Claus Lindbjerg Andersen, Aarhus University Hospital

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

Claus Lindbjerg Andersen

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

University of Aarhus

Investigators ^ICMJE

Principal Investigator:

Claus L Andersen, PhD

Department of Molecular Medicin, Aarhus University Hospital

PRS Account

University of Aarhus

Verification Date

June 2022

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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