OPTIMIzation of Treatment SElection and Follow up in Oligometastatic Colorectal Cancer

Phase 2

Recruiting

• Conditions: Colorectal Cancer; Metastatic Cancer
• Interventions: Other: Circulating tumor DNA guided treatment approach; Other: Standard of care

• Registration Number: NCT04680260
• Lead Sponsor: Karen-Lise Garm Spindler

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.

Study Timeline

• Study First Submitted: 2020-10-19
• Study First Submitted QC: 2020-12-21
• Study First Posted: 2020-12-22
• Study Start: 2021-10-25
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-13
• Last Update Posted: 2024-08-14
• Primary Completion: 2027-03-01
• Study Completion: 2030-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 350

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B: ctDNA guided therapy approach	Circulating tumor DNA guided treatment approach	Post ablation ctDNA results will be used for treatment decision.
A: Standard of care	Standard of care	Standard decision making regarding adjuvant chemotherapy with fluoropyrimidine and oxaliplatin as per institutional standards.

Primary Outcome Measures

Name	Time	Method
Recurrence Free Rate	2 years	Rate of patients free from recurrent colorectal cancer at 2 years post local treatment

Secondary Outcome Measures

Name	Time	Method
Time to molecular biological recurrence	5 years last patient	Time to molecular biological recurrence is calculated from first time of no detectable DNA until detectable DNA in a samples
Time to radiological recurrence	5 years last patient	Time to radiological recurrence is calculated from inclusion until radiological evidence of disease recurrence
Molecular biological response to therapy	6 months post-treatment	Rate of patients with lack of detectable tumor DNA in plasma samples
Local and distant relapse	5 years last patient	Rate of patients with local and distant relapse
Overall survival	5 years last patient	Time from inclusion to death from any cause
Quality of life according to EQ-5D-5L	5 years last patient	The EQ-5D-5L essentially consists of: the EQ-5D descriptive system and the EQ visual analogue scale. The descriptive system comprises 5 dimensions. Each dimension has 5 levels. The patient is asked to indicate his/her health. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the 5 dimensions can be combined into a 5-digit number that describes the patient's health state.The EQ VAS records the patient's self-rated health on a vertical visual analogue scale.
Molecular biological Disease Free Survival	1 year from inclusion	Rate of patients with no detectable ctDNA
Toxicity of treatment	6 months post-treatment	Rate of grade 3-4 toxicity according to CTCAE version 5
Cost-effectiveness analysis	5 years last patient	Economic evaluation of ctDNA guided chemotherapy after curative treatment of metastatic colorectal cancer
Quality of life according to EORTC QLQ-CR29 and -C30	5 years last patient	The EORTC QLQ-CR29 is a tumor-specific health related QoL questionnaire module for CRC patients, which complement the EORTC QLQ-C30 questionnaire. Patients indicate their symptoms during the past week(s). Scores can be linearly transformed to a score from 0-100. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales.

Trial Locations

Locations (2)

Department of Oncology, Aarhus University Hospital; 🇩🇰 Aarhus N, Denmark

Department pf Oncology, Vejle Hospital; 🇩🇰 Vejle, Denmark