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

Colorectal Cancer Clinical Trial

— IMPROVE-IT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03748680
• Other study ID #: KFE-1803
• Status: Recruiting
• Phase: Phase 2
• Start date: October 1, 2018
• Est. completion date: October 1, 2025

Study information

• Verified date: February 2022
• Source: Aarhus University Hospital
• Contact: Karen-Lise G Spindler, Professor
• Phone: 0045 7846 2535
• Email: k.g.spindler[@]rm.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: October 1, 2025
• Est. primary completion date: October 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adjuvant Chemotherapy
• Circulating Tumor DNA
• Colorectal Cancer
• Colorectal Neoplasms
• Progression Free Survival

Intervention

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)

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.

Locations

Country	Name	City	State
Denmark	Aalborg University Hospital	Aalborg
Denmark	Aarhus University Hospital	Aarhus
Denmark	Herlev Hospital	Herlev
Denmark	Odense University Hospital	Odense

Sponsors (1)

Lead Sponsor	Collaborator
Karen-Lise Garm Spindler

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DFS	Disease free survival	3 years
Secondary	Molecular biological response	Molecular biological response at 6 months	6 months
Secondary	MB-DFS	Molecular biological disease free survival at 1 year	1 year
Secondary	TT-MBR	Time to molecular biological recurrence	3 years
Secondary	TTR	Time to radiological recurrence	3 years
Secondary	LRR	Local recurrence rate	3 years
Secondary	DRR	Distant recurrence rate	3 years
Secondary	OS	Overall survival	5 years
Secondary	TR	Translational research exploratory	3 years