Back to resultsOPTIMIzation of Treatment SElection and Follow up in Oligometastatic Colorectal Cancer (OPTIMISE)
Primary Purpose
Colorectal Cancer, Metastatic Cancer
Status
Recruiting
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Standard of care
Circulating tumor DNA guided treatment approach
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring Circulating tumor DNA, Adjuvant chemotherapy, Colorectal cancer, Metastatic
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)
- 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
Sites / Locations
- Department of Oncology, Aarhus University HospitalRecruiting
- Department pf Oncology, Vejle HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
A: Standard of care
B: ctDNA guided therapy approach
Arm Description
Standard decision making regarding adjuvant chemotherapy with fluoropyrimidine and oxaliplatin as per institutional standards.
Post ablation ctDNA results will be used for treatment decision.
Outcomes
Primary Outcome Measures
Recurrence Free Rate
Rate of patients free from recurrent colorectal cancer at 2 years post local treatment
Secondary Outcome Measures
Toxicity of treatment
Rate of grade 3-4 toxicity according to CTCAE version 5
Molecular biological response to therapy
Rate of patients with lack of detectable tumor DNA in plasma samples
Molecular biological Disease Free Survival
Rate of patients with no detectable ctDNA
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
Time to radiological recurrence
Time to radiological recurrence is calculated from inclusion until radiological evidence of disease recurrence
Local and distant relapse
Rate of patients with local and distant relapse
Overall survival
Time from inclusion to death from any cause
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.
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.
Cost-effectiveness analysis
Economic evaluation of ctDNA guided chemotherapy after curative treatment of metastatic colorectal cancer
Full Information
NCT ID
NCT04680260
First Posted
October 19, 2020
Last Updated
February 7, 2023
Sponsor
Karen-Lise Garm Spindler
Collaborators
Vejle Hospital, Zealand University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04680260
Brief Title
OPTIMIzation of Treatment SElection and Follow up in Oligometastatic Colorectal Cancer
Acronym
OPTIMISE
Official Title
OPTIMIzation of Treatment SElection and Follow up in Oligometastatic Colorectal Cancer - a ctDNA Guided Phase II Randomized Approach
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 25, 2021 (Actual)
Primary Completion Date
March 1, 2027 (Anticipated)
Study Completion Date
March 1, 2030 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Karen-Lise Garm Spindler
Collaborators
Vejle Hospital, Zealand University Hospital
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Metastatic Cancer
Keywords
Circulating tumor DNA, Adjuvant chemotherapy, Colorectal cancer, Metastatic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
An open label 1:1 randomized phase II exploratory study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
350 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
A: Standard of care
Arm Type
Active Comparator
Arm Description
Standard decision making regarding adjuvant chemotherapy with fluoropyrimidine and oxaliplatin as per institutional standards.
Arm Title
B: ctDNA guided therapy approach
Arm Type
Experimental
Arm Description
Post ablation ctDNA results will be used for treatment decision.
Intervention Type
Other
Intervention Name(s)
Standard of care
Intervention Description
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
Intervention Name(s)
Circulating tumor DNA guided treatment approach
Intervention Description
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.
Primary Outcome Measure Information:
Title
Recurrence Free Rate
Description
Rate of patients free from recurrent colorectal cancer at 2 years post local treatment
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Toxicity of treatment
Description
Rate of grade 3-4 toxicity according to CTCAE version 5
Time Frame
6 months post-treatment
Title
Molecular biological response to therapy
Description
Rate of patients with lack of detectable tumor DNA in plasma samples
Time Frame
6 months post-treatment
Title
Molecular biological Disease Free Survival
Description
Rate of patients with no detectable ctDNA
Time Frame
1 year from inclusion
Title
Time to molecular biological recurrence
Description
Time to molecular biological recurrence is calculated from first time of no detectable DNA until detectable DNA in a samples
Time Frame
5 years last patient
Title
Time to radiological recurrence
Description
Time to radiological recurrence is calculated from inclusion until radiological evidence of disease recurrence
Time Frame
5 years last patient
Title
Local and distant relapse
Description
Rate of patients with local and distant relapse
Time Frame
5 years last patient
Title
Overall survival
Description
Time from inclusion to death from any cause
Time Frame
5 years last patient
Title
Quality of life according to EORTC QLQ-CR29 and -C30
Description
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.
Time Frame
5 years last patient
Title
Quality of life according to EQ-5D-5L
Description
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.
Time Frame
5 years last patient
Title
Cost-effectiveness analysis
Description
Economic evaluation of ctDNA guided chemotherapy after curative treatment of metastatic colorectal cancer
Time Frame
5 years last patient
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Karen-Lise G Spindler, Professor
Phone
+4591167244
Email
k.g.spindler@rm.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karen-Lise G Spindler, Professor
Organizational Affiliation
Department of Oncology, Aarhus University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Oncology, Aarhus University Hospital
City
Aarhus N
ZIP/Postal Code
8200
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Louise B Callesen, MD
Facility Name
Department pf Oncology, Vejle Hospital
City
Vejle
ZIP/Postal Code
7100
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Torben F Hansen, MD, Ass. Prof.
12. IPD Sharing Statement
Learn more about this trial
OPTIMIzation of Treatment SElection and Follow up in Oligometastatic Colorectal Cancer
We'll reach out to this number within 24 hrs