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

Primary Purpose

Colorectal Cancer, Circulating Tumor DNA, Adjuvant Chemotherapy

Status
Recruiting
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapy
Intensified Follow-up Schedule
Sponsored by
Karen-Lise Garm Spindler
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer

Eligibility Criteria

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

Inclusion Criteria:

  • Surgically removed Adenocarcinoma of the colon or rectum
  • Pathologically stage I or II disease, and radical resection
  • Detectable ctDNA in two weeks postoperative plasma sample
  • No indication for adjuvant chemotherapy according to DCCG guidelines (website)
  • Age at least 18 years
  • ECOG performance status 0-2
  • Clinically eligible for adjuvant chemotherapy at investigators decision.
  • Adequate bone marrow, liver and renal function allowing systemic chemotherapy (Absolute neutrophil count ≥1.5x109/l and thrombocytes ≥ 100x109/l. Bilirubin ≤ 1.5 x upper normal value and alanine aminotransferase ≤ 3 x upper normal value, and Calculated or measured renal glomerular filtration rate at least 30 mL/min)
  • Anticonception for fertile women and for male patients with a fertile partner. Intrauterine device, vasectomy of a female subject's male partner or hormonal contraceptive are acceptable •
  • Written and verbally informed consent

Exclusion Criteria:

  • Radiological evidence of distant metastasis, by CT- chest and abdomen
  • Incapacity, frailty, disability and comorbidity to a degree that according to the investigator is not compatible with combination chemotherapy
  • Previous treatment with 5FU or oxaliplatin
  • Neuropathy NCI grade > 1
  • Other malignant tumor within 5 years except non-melanoma skin cancer or carcinoma in situ cervicis uteri
  • Pregnant (positive pregnancy test) or breast feeding women

Sites / Locations

  • Aalborg University HospitalRecruiting
  • Aarhus University HospitalRecruiting
  • Herlev HospitalRecruiting
  • Odense University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

A

B

Arm Description

Intensified follow-up schedule

Adjuvant chemotherapy + intensified follow-up schedule

Outcomes

Primary Outcome Measures

DFS
Disease free survival

Secondary Outcome Measures

Molecular biological response
Molecular biological response at 6 months
MB-DFS
Molecular biological disease free survival at 1 year
TT-MBR
Time to molecular biological recurrence
TTR
Time to radiological recurrence
LRR
Local recurrence rate
DRR
Distant recurrence rate
OS
Overall survival
TR
Translational research exploratory

Full Information

First Posted
November 19, 2018
Last Updated
February 24, 2022
Sponsor
Karen-Lise Garm Spindler
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1. Study Identification

Unique Protocol Identification Number
NCT03748680
Brief Title
IMPROVE Intervention Trial Implementing Non-invasive Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer
Acronym
IMPROVE-IT
Official Title
Implementing Non-invasive Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2018 (Actual)
Primary Completion Date
October 1, 2023 (Anticipated)
Study Completion Date
October 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Karen-Lise Garm Spindler

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A open label 1:1 randomized phase II exploratory study investigating adjuvant therapy in patients with molecular biologically detectable residual disease after primary resection for localized colorectal tumors.
Detailed Description
The main clinical hypothesis is that patients having undergone radical resection from CRC do not present with detectable tumor DNA in the plasma, whereas patients with detectable tumor DNA two weeks' post surgery have residual microscopic disease, and consequently a high risk of diseases recurrence which can be prevented with adjuvant chemotherapy. The primary aim of the present study is to investigate - in a randomized trial - if use of standard adjuvant chemotherapy therapy improves the disease free survival in patients with molecular biological residual disease where adjuvant chemotherapy is not standard treatment . Secondary aims include investigating molecular biological response to adjuvant chemotherapy in patients with post-operative ctDNA.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Circulating Tumor DNA, Adjuvant Chemotherapy, Progression Free Survival

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
A open label 1:1 randomized phase II exploratory study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
64 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Active Comparator
Arm Description
Intensified follow-up schedule
Arm Title
B
Arm Type
Experimental
Arm Description
Adjuvant chemotherapy + intensified follow-up schedule
Intervention Type
Drug
Intervention Name(s)
Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapy
Intervention Description
Six months of adjuvant combination chemotherapy with Capox (or FOLFOX) Patients will receive adjuvant chemotherapy with eight cycles of CAPOX (oxaliplatin 130 mg/m2 day 1 and capecitabine 1000 mg/m2 b.i.d. days 1-14, repeated every 3 weeks. (Patients with an ileostomy are only eligible for FOLFOX and will be treated with 12 cycles of FOLFOX (oxaliplatin 85 mg/m2 day 1, leucovorin 400 mg/m2 day 1, 5FU 400 mg/m2 bolus day 1 and 5FU 2400 mg/ m2 over 46-48 hours day 1-3, repeated every second weeks)
Intervention Type
Other
Intervention Name(s)
Intensified Follow-up Schedule
Intervention Description
Close monitoring with Imaging during follow-up Patients included in this trial will undergo intensified follow-up with CT-chest and abdomen every four months after surgery for the first 2 years, then every 6 months for 1 years and finally once yearly for the last 2 years up to 5 years follow-up is completed.
Primary Outcome Measure Information:
Title
DFS
Description
Disease free survival
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Molecular biological response
Description
Molecular biological response at 6 months
Time Frame
6 months
Title
MB-DFS
Description
Molecular biological disease free survival at 1 year
Time Frame
1 year
Title
TT-MBR
Description
Time to molecular biological recurrence
Time Frame
3 years
Title
TTR
Description
Time to radiological recurrence
Time Frame
3 years
Title
LRR
Description
Local recurrence rate
Time Frame
3 years
Title
DRR
Description
Distant recurrence rate
Time Frame
3 years
Title
OS
Description
Overall survival
Time Frame
5 years
Title
TR
Description
Translational research exploratory
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Surgically removed Adenocarcinoma of the colon or rectum Pathologically stage I or II disease, and radical resection Detectable ctDNA in two weeks postoperative plasma sample No indication for adjuvant chemotherapy according to DCCG guidelines (website) Age at least 18 years ECOG performance status 0-2 Clinically eligible for adjuvant chemotherapy at investigators decision. Adequate bone marrow, liver and renal function allowing systemic chemotherapy (Absolute neutrophil count ≥1.5x109/l and thrombocytes ≥ 100x109/l. Bilirubin ≤ 1.5 x upper normal value and alanine aminotransferase ≤ 3 x upper normal value, and Calculated or measured renal glomerular filtration rate at least 30 mL/min) Anticonception for fertile women and for male patients with a fertile partner. Intrauterine device, vasectomy of a female subject's male partner or hormonal contraceptive are acceptable • Written and verbally informed consent Exclusion Criteria: Radiological evidence of distant metastasis, by CT- chest and abdomen Incapacity, frailty, disability and comorbidity to a degree that according to the investigator is not compatible with combination chemotherapy Previous treatment with 5FU or oxaliplatin Neuropathy NCI grade > 1 Other malignant tumor within 5 years except non-melanoma skin cancer or carcinoma in situ cervicis uteri Pregnant (positive pregnancy test) or breast feeding women
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Karen-Lise G Spindler, Professor
Phone
0045 7846 2535
Ext
+4578462535
Email
k.g.spindler@rm.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Karen-Lise G Spindler, Professor
Phone
+4578462535
Ext
+4578462535
Email
k.g.spindler@rm.dk
Facility Information:
Facility Name
Aalborg University Hospital
City
Aalborg
Country
Denmark
Individual Site Status
Recruiting
Facility Name
Aarhus University Hospital
City
Aarhus
ZIP/Postal Code
8000
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karen-Lise G Spindler, Prof.
Phone
+457846 2535
Email
k.g.spindler@rm.dk
First Name & Middle Initial & Last Name & Degree
Line M Sparvath, CRN
Phone
457846 2610
Email
linspa@rm.dk
First Name & Middle Initial & Last Name & Degree
Søren Lauerberg, Prof.
First Name & Middle Initial & Last Name & Degree
Claus L Andersen, Prof.
Facility Name
Herlev Hospital
City
Herlev
Country
Denmark
Individual Site Status
Recruiting
Facility Name
Odense University Hospital
City
Odense
Country
Denmark
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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

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