OPTIMIzation of Treatment SElection and Follow up in Oligometastatic Colorectal Cancer

Colorectal Cancer Clinical Trial

— OPTIMISE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04680260
• Other study ID #: KFE2022
• Status: Recruiting
• Phase: Phase 2
• Start date: October 25, 2021
• Est. completion date: March 1, 2030

Study information

• Verified date: February 2023
• Source: Aarhus University Hospital
• Contact: Karen-Lise G Spindler, Professor
• Phone: +4591167244
• Email: k.g.spindler[@]rm.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: March 1, 2030
• Est. primary completion date: March 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Metastatic Cancer

Intervention

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.
• 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.

Locations

Country	Name	City	State
Denmark	Department of Oncology, Aarhus University Hospital	Aarhus N
Denmark	Department pf Oncology, Vejle Hospital	Vejle

Sponsors (3)

Lead Sponsor	Collaborator
Karen-Lise Garm Spindler	Vejle Hospital, Zealand University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence Free Rate	Rate of patients free from recurrent colorectal cancer at 2 years post local treatment	2 years
Secondary	Toxicity of treatment	Rate of grade 3-4 toxicity according to CTCAE version 5	6 months post-treatment
Secondary	Molecular biological response to therapy	Rate of patients with lack of detectable tumor DNA in plasma samples	6 months post-treatment
Secondary	Molecular biological Disease Free Survival	Rate of patients with no detectable ctDNA	1 year from inclusion
Secondary	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
Secondary	Time to radiological recurrence	Time to radiological recurrence is calculated from inclusion until radiological evidence of disease recurrence	5 years last patient
Secondary	Local and distant relapse	Rate of patients with local and distant relapse	5 years last patient
Secondary	Overall survival	Time from inclusion to death from any cause	5 years last patient
Secondary	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
Secondary	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
Secondary	Cost-effectiveness analysis	Economic evaluation of ctDNA guided chemotherapy after curative treatment of metastatic colorectal cancer	5 years last patient