OPTIMIzation of Treatment SElection and Follow up in Oligometastatic Colorectal Cancer

NCT ID: NCT04680260

Last Updated: 2024-08-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-25
• Study Completion Date: 2030-03-01

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.

Conditions

Colorectal Cancer; Metastatic Cancer

Study Design

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

Study Groups

A: Standard of care

Standard decision making regarding adjuvant chemotherapy with fluoropyrimidine and oxaliplatin as per institutional standards.

Group Type: ACTIVE_COMPARATOR

Standard of care

Intervention Type: OTHER

Patients will be offered adjuvant chemotherapy according to standard of care. Follow up will be performed with imaging according to standard guidelines, equal to the experimental arm. Blood samples will be analyzed retrospectively to evaluate the ctDNA status.

B: ctDNA guided therapy approach

Post ablation ctDNA results will be used for treatment decision.

Group Type: EXPERIMENTAL

Circulating tumor DNA guided treatment approach

Intervention Type: OTHER

Circulating tumor-marker positivity will lead to escalation with 6 months of intensified chemotherapy consisting of 4 months of FOLFOXIRI followed by 2 months of 5FU monotherapy. Circulating tumor-marker negativity will based on shared decision-making lead to de-escalation i.e. possibilities for observation in patients otherwise eligible for monotherapy or observation/monotherapy in patients, otherwise eligible for combination chemotherapy according to standard of care.

Interventions

Standard of care

Patients will be offered adjuvant chemotherapy according to standard of care. Follow up will be performed with imaging according to standard guidelines, equal to the experimental arm. Blood samples will be analyzed retrospectively to evaluate the ctDNA status.

Intervention Type: OTHER

Circulating tumor DNA guided treatment approach

Circulating tumor-marker positivity will lead to escalation with 6 months of intensified chemotherapy consisting of 4 months of FOLFOXIRI followed by 2 months of 5FU monotherapy. Circulating tumor-marker negativity will based on shared decision-making lead to de-escalation i.e. possibilities for observation in patients otherwise eligible for monotherapy or observation/monotherapy in patients, otherwise eligible for combination chemotherapy according to standard of care.

Intervention Type: OTHER

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

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

Sponsors

Vejle Hospital

OTHER

Sponsor Role: collaborator

Zealand University Hospital

OTHER

Sponsor Role: collaborator

Karen-Lise Garm Spindler

OTHER

Sponsor Role: lead

Responsible Party

Karen-Lise Garm Spindler

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Karen-Lise G Spindler, Professor

Role: PRINCIPAL_INVESTIGATOR

Department of Oncology, Aarhus University Hospital

Locations

Department of Oncology, Aarhus University Hospital

Aarhus N, , Denmark

Site Status: RECRUITING

Department pf Oncology, Vejle Hospital

Vejle, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Karen-Lise G Spindler, Professor

Role: CONTACT

k.g.spindler@rm.dk

+4591167244

Facility Contacts

Louise B Callesen, MD

Role: primary

Torben F Hansen, MD, Ass. Prof.

Role: primary

Other Identifiers

KFE2022

Identifier Type: -

Identifier Source: org_study_id