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

NCT ID: NCT03748680

Last Updated: 2022-02-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-01
• Study Completion Date: 2025-10-01

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.

Conditions

Colorectal Cancer; Circulating Tumor DNA; Adjuvant Chemotherapy; Progression Free Survival

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

Intensified follow-up schedule

Group Type: ACTIVE_COMPARATOR

Intensified Follow-up Schedule

Intervention Type: OTHER

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.

B

Adjuvant chemotherapy + intensified follow-up schedule

Group Type: EXPERIMENTAL

Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapy

Intervention Type: DRUG

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)

Interventions

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)

Intervention Type: DRUG

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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karen-Lise Garm Spindler

OTHER

Sponsor Role: lead

Responsible Party

Karen-Lise Garm Spindler

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Aalborg University Hospital

Aalborg, , Denmark

Site Status: RECRUITING

Aarhus University Hospital

Aarhus, , Denmark

Site Status: RECRUITING

Herlev Hospital

Herlev, , Denmark

Site Status: RECRUITING

Odense University Hospital

Odense, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Karen-Lise G Spindler, Professor

Role: CONTACT

k.g.spindler@rm.dk

0045 7846 2535 ext. +4578462535

Karen-Lise G Spindler, Professor

Role: CONTACT

k.g.spindler@rm.dk

+4578462535 ext. +4578462535

Facility Contacts

Karen-Lise G Spindler, Prof.

Role: primary

k.g.spindler@rm.dk

+457846 2535

Line M Sparvath, CRN

Role: backup

linspa@rm.dk

457846 2610

Other Identifiers

KFE-1803

Identifier Type: -

Identifier Source: org_study_id