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

Sponsor

Karen-Lise Garm Spindler (Other)

Overall Status

Recruiting

CT.gov ID

NCT03748680

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Circulating Tumor DNA Adjuvant Chemotherapy Progression Free Survival	Drug: Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapy Other: Intensified Follow-up Schedule	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

64 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

A open label 1:1 randomized phase II exploratory studyA open label 1:1 randomized phase II exploratory study

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 1, 2018

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A Intensified follow-up schedule	Other: Intensified Follow-up Schedule 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.
Experimental: B Adjuvant chemotherapy + intensified follow-up schedule	Drug: Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapy 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)

Arm

Intervention/Treatment

Active Comparator: A

Intensified follow-up schedule

Other: Intensified Follow-up Schedule

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.

Experimental: B

Adjuvant chemotherapy + intensified follow-up schedule

Drug: Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapy

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)

Outcome Measures

Primary Outcome Measures

DFS [3 years]
Disease free survival

Secondary Outcome Measures

Molecular biological response [6 months]
Molecular biological response at 6 months
MB-DFS [1 year]
Molecular biological disease free survival at 1 year
TT-MBR [3 years]
Time to molecular biological recurrence
TTR [3 years]
Time to radiological recurrence
LRR [3 years]
Local recurrence rate
DRR [3 years]
Distant recurrence rate
OS [5 years]
Overall survival
TR [3 years]
Translational research exploratory

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Aalborg University Hospital	Aalborg	Denmark
2	Aarhus University Hospital	Aarhus	Denmark	8000
3	Herlev Hospital	Herlev	Denmark
4	Odense University Hospital	Odense	Denmark

Sponsors and Collaborators

Karen-Lise Garm Spindler

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Karen-Lise Garm Spindler, Professor, Aarhus University Hospital

ClinicalTrials.gov Identifier:

NCT03748680

Other Study ID Numbers:

KFE-1803

First Posted:

Nov 21, 2018

Last Update Posted:

Feb 25, 2022

Last Verified:

Feb 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Colorectal Neoplasms

Oxaliplatin

Study Results

No Results Posted as of Feb 25, 2022