OPTIMIzation of Treatment SElection and Follow up in Oligometastatic Colorectal Cancer (OPTIMISE)

OPTIMIzation of Treatment SElection and Follow up in Oligometastatic Colorectal Cancer - a ctDNA Guided Phase II Randomized Approach

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

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Metastatic Cancer
• Intervention / Treatment: Other: Standard of care; Other: Circulating tumor DNA guided treatment approach

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 Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Karen-Lise G Spindler, Professor; Phone Number: +4591167244; Email: k.g.spindler@rm.dk

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Recruiting
    • Department of Oncology, Aarhus University Hospital
    • Contact: Louise B Callesen, MD
  • Vejle, Denmark, 7100
    • Recruiting
    • Department pf Oncology, Vejle Hospital
    • Contact: Torben F Hansen, MD, Ass. Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A: Standard of care; Standard decision making regarding adjuvant chemotherapy with fluoropyrimidine and oxaliplatin as per institutional standards.	Other: 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.
Experimental: B: ctDNA guided therapy approach; Post ablation ctDNA results will be used for treatment decision.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence Free Rate	Rate of patients free from recurrent colorectal cancer at 2 years post local treatment	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity of treatment	Rate of grade 3-4 toxicity according to CTCAE version 5	6 months post-treatment
Molecular biological response to therapy	Rate of patients with lack of detectable tumor DNA in plasma samples	6 months post-treatment
Molecular biological Disease Free Survival	Rate of patients with no detectable ctDNA	1 year from inclusion
Time to molecular biological recurrence	Time to molecular biological recurrence is calculated from first time of no detectable DNA until detectable DNA in a samples	5 years last patient
Time to radiological recurrence	Time to radiological recurrence is calculated from inclusion until radiological evidence of disease recurrence	5 years last patient
Local and distant relapse	Rate of patients with local and distant relapse	5 years last patient
Overall survival	Time from inclusion to death from any cause	5 years last patient
Cost-effectiveness analysis	Economic evaluation of ctDNA guided chemotherapy after curative treatment of metastatic colorectal cancer	5 years last patient
Quality of life according to EORTC QLQ-CR29 and -C30	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.	5 years last patient
Quality of life according to EQ-5D-5L	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.	5 years last patient

Collaborators and Investigators

• Sponsor: Karen-Lise Garm Spindler
• Collaborators: Zealand University Hospital; Vejle Hospital
• Investigators: Principal Investigator: Karen-Lise G Spindler, Professor, Department of Oncology, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2021
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: October 19, 2020
• First Submitted That Met QC Criteria: December 21, 2020
• First Posted (Actual): December 22, 2020

Study Record Updates

• Last Update Posted (Actual): August 14, 2024
• Last Update Submitted That Met QC Criteria: August 13, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Colorectal cancer; Adjuvant chemotherapy; Metastatic; Circulating tumor DNA
• 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
• Other Study ID Numbers: KFE2022

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