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

Primary Purpose

Colorectal Cancer, Colo-rectal Cancer, ctDNA

Status
Recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
ctDNA-analysis
Intensified Follow-up Schedule
Sponsored by
Claus Lindbjerg Andersen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Colorectal Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Surgical Department, Randers Regional HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

ctDNA guided surveillance

Standard Danish follow-up program

Arm Description

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.

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
September 4, 2019
Last Updated
August 15, 2023
Sponsor
Claus Lindbjerg Andersen
Collaborators
University of Aarhus
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1. Study Identification

Unique Protocol Identification Number
NCT04084249
Brief Title
Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer - Intervention Trial 2
Acronym
IMPROVE-IT2
Official Title
Implementing Non-invasive Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer - Intervention Trial 2
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2020 (Actual)
Primary Completion Date
June 30, 2028 (Anticipated)
Study Completion Date
June 30, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Claus Lindbjerg Andersen
Collaborators
University of Aarhus

4. Oversight

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

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
340 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ctDNA guided surveillance
Arm Type
Experimental
Arm Description
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.
Arm Title
Standard Danish follow-up program
Arm Type
No Intervention
Arm Description
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).
Intervention Type
Diagnostic Test
Intervention Name(s)
ctDNA-analysis
Intervention Description
Minimally-invasive blood-based analysis of circulating tumor DNA (ctDNA).
Intervention Type
Other
Intervention Name(s)
Intensified Follow-up Schedule
Intervention Description
PET/CT-scans every 3. month
Primary Outcome Measure Information:
Title
FCI
Description
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 Outcome Measure Information:
Title
3yr-OS
Description
Overall survival at 3 years
Time Frame
3 years
Title
5yr-OS
Description
Overall survival at 5 years
Time Frame
5 years
Title
TTCR
Description
Time to clinical recurrence
Time Frame
3 years
Title
TTMR
Description
Time to molecular recurrence
Time Frame
2 years
Title
QoL
Description
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
Title
FCRI
Description
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
Title
IES-C
Description
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
Title
CE
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Claus L Andersen, PhD
Phone
+45 78455319
Email
cla@clin.au.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Kaare A Gotschalck, PhD
Phone
+45 78423786
Email
kaarsune@rm.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claus L Andersen, PhD
Organizational Affiliation
Department of Molecular Medicin, Aarhus University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Surgical Department, Randers Regional Hospital
City
Randers
ZIP/Postal Code
8930
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kaare Andersson Gotschalck, MD, PhD
Ext
+45
Email
kaarsune@rm.dk
First Name & Middle Initial & Last Name & Degree
Jesper Nors, MD
Phone
c
Ext
+45
Email
jenors@rm.dk

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31920137
Citation
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.
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Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer - Intervention Trial 2

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