Clinical trial NCT04680260: OPTIMIzation of Treatment SElection and Follow up in Oligometastatic Colorectal Cancer
Official title: OPTIMIzation of Treatment SElection and Follow up in Oligometastatic Colorectal Cancer - a ctDNA Guided Phase II Randomized Approach
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colorectal Cancer
Metastatic Cancer
Keywords: Circulating tumor DNA
Adjuvant chemotherapy
Colorectal cancer
Metastatic
Lead sponsor: Aarhus University Hospital
Sponsor class: OTHER
Collaborators: name: Vejle Hospital
name: Zealand University Hospital
First posted: 2020-12-22
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: An open label 1:1 randomized phase II exploratory study
Primary purpose: TREATMENT

Brief summary: A study investigating if analysis of circulating tumor DNA (ctDNA) can guide adjuvant treatment in patients with advanced colorectal cancer (CRC)

Detailed description: An open label 1:1 randomized phase II exploratory study investigating use of ctDNA-guided adjuvant chemotherapy compared to standard of care (SOC) after local treatment for metastatic colorectal cancer.

Patients are randomized 1:1 between SOC and ctDNA guided treatment and follow-up.

Escalation therapy comprises standard regimen of Fluorouracil (5-FU), Irinotecan and oxaliplatin (FOLFOXIRI), de-escalation therapy of monotherapy capecitabine or observation only. SOC is per institutional practice, based on national guidelines.

Eligibility criteria: Inclusion Criteria:

* Radical intended treatment for metastatic spread from CRC, by resection, radiofrequency ablation, stereotactic body radiation therapy (or other experimental local treatment options) not including cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC)
* No evidence of further disease based on pre-treatment work-up according to SOC
* Age at least 18 years
* Eastern Cooperative Oncology Group performance status 0-2
* Clinically eligible for adjuvant triple CT 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, abdomen, and pelvis
* Incapacity, frailty, disability and comorbidity to a degree that according to the investigator is not compatible with triple combination chemotherapy
* Neuropathy National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 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
* Intolerance or allergy to 5FU, leucovorin, oxaliplatin, irinotecan or capecitabine

Primary outcomes:
measure: Recurrence Free Rate
timeFrame: 2 years
Secondary outcomes:
measure: Toxicity of treatment
timeFrame: 6 months post-treatment
measure: Molecular biological response to therapy
timeFrame: 6 months post-treatment
measure: Molecular biological Disease Free Survival
timeFrame: 1 year from inclusion
measure: Time to molecular biological recurrence
timeFrame: 5 years last patient
measure: Time to radiological recurrence
timeFrame: 5 years last patient
measure: Local and distant relapse
timeFrame: 5 years last patient
measure: Overall survival
timeFrame: 5 years last patient
measure: Quality of life according to EORTC QLQ-CR29 and -C30
timeFrame: 5 years last patient
measure: Quality of life according to EQ-5D-5L
timeFrame: 5 years last patient
measure: Cost-effectiveness analysis
timeFrame: 5 years last patient
Other outcomes:
Locations:
city: Aarhus N
country: Denmark
facility: Department of Oncology, Aarhus University Hospital
city: Vejle
country: Denmark
facility: Department pf Oncology, Vejle Hospital
Study officials:
affiliation: Department of Oncology, Aarhus University Hospital
name: Karen-Lise G Spindler, Professor
role: PRINCIPAL_INVESTIGATOR
References: