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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Adjuvant Chemotherapy; Circulating Tumor DNA; Progression Free Survival
• Intervention / Treatment: Other: Intensified Follow-up Schedule; Drug: Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapy

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 Type: Interventional
• Enrollment (Anticipated): 64
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Karen-Lise G Spindler, Professor; Phone Number: +4578462535 0045 7846 2535; Email: k.g.spindler@rm.dk
• Study Contact Backup: Name: Karen-Lise G Spindler, Professor; Phone Number: +4578462535 +4578462535; Email: k.g.spindler@rm.dk

Study Locations

• Denmark
  • Aalborg, Denmark
    • Recruiting
    • Aalborg University Hospital
  • Aarhus, Denmark, 8000
    • Recruiting
    • Aarhus University Hospital
    • Contact: Karen-Lise G Spindler, Prof.; Phone Number: +457846 2535; Email: k.g.spindler@rm.dk
    • Contact: Line M Sparvath, CRN; Phone Number: 457846 2610; Email: linspa@rm.dk
    • Sub-Investigator: Søren Lauerberg, Prof.
    • Sub-Investigator: Claus L Andersen, Prof.
  • Herlev, Denmark
    • Recruiting
    • Herlev Hospital
  • Odense, Denmark
    • Recruiting
    • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DFS	Disease free survival	3 years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Karen-Lise Garm Spindler

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2018
• Primary Completion (ANTICIPATED): October 1, 2023
• Study Completion (ANTICIPATED): October 1, 2025

Study Registration Dates

• First Submitted: November 19, 2018
• First Submitted That Met QC Criteria: November 19, 2018
• First Posted (ACTUAL): November 21, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 25, 2022
• Last Update Submitted That Met QC Criteria: February 24, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Oxaliplatin
• Other Study ID Numbers: KFE-1803

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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