Clinical trial NCT03748680: IMPROVE Intervention Trial Implementing Non-invasive Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer
Official title: Implementing Non-invasive Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colorectal Cancer
Circulating Tumor DNA
Adjuvant Chemotherapy
Progression Free Survival
Lead sponsor: Aarhus University Hospital
Sponsor class: OTHER
First posted: 2018-11-21
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A open label 1:1 randomized phase II exploratory study
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: DFS
timeFrame: 3 years
Secondary outcomes:
measure: Molecular biological response
timeFrame: 6 months
measure: MB-DFS
timeFrame: 1 year
measure: TT-MBR
timeFrame: 3 years
measure: TTR
timeFrame: 3 years
measure: LRR
timeFrame: 3 years
measure: DRR
timeFrame: 3 years
measure: OS
timeFrame: 5 years
measure: TR
timeFrame: 3 years
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
References: