Colorectal CancerPhase 2OPTIMISENCT04680260
OPTIMIzation of Treatment SElection and Follow up in Oligometastatic Colorectal Cancer
A Phase 2 study testing Circulating tumor DNA guided treatment approach in people with Colorectal Cancer and Metastatic Cancer, run by Karen-Lise Garm Spindler at 2 sites in Denmark.
Trial summary
A study investigating if analysis of circulating tumor DNA (ctDNA) can guide adjuvant treatment in patients with advanced colorectal cancer (CRC) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Metastatic Cancer
- What is being tested?
- Circulating tumor DNA guided treatment approach
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 350 participants
- Where
- 2 sitesDenmark
- Study dates
- 25 Oct 2021to 1 Mar 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark2 sites, 2 recruiting
- Recruiting
Department of Oncology, Aarhus University Hospital
Aarhus N, 8200
Louise B Callesen, MD
- Recruiting
Department pf Oncology, Vejle Hospital
Vejle, 7100
Torben F Hansen, MD, Ass. Prof.
About this study
Official title: 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)
Read the 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
- Being tested
- Standard of care, Circulating tumor DNA guided treatment approach
- Keywords
- Circulating tumor DNA, Adjuvant chemotherapy, Colorectal cancer, Metastatic
- Medical subject headings
- Colorectal Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of careOther
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 approachOther
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.
| Study group | Role | What they receive |
|---|---|---|
| A: Standard of care | Active comparator | Standard decision making regarding adjuvant chemotherapy with fluoropyrimidine and oxaliplatin as per institutional standards. Receives: Other: Standard of care |
| B: ctDNA guided therapy approach | Experimental | Post ablation ctDNA results will be used for treatment decision. Receives: Other: Circulating tumor DNA guided treatment approach |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence Free Rate
Rate of patients free from recurrent colorectal cancer at 2 years post local treatment
Measured: 2 years
Secondary outcomes (10)
Toxicity of treatment
Rate of grade 3-4 toxicity according to CTCAE version 5
Measured: 6 months post-treatment
Molecular biological response to therapy
Rate of patients with lack of detectable tumor DNA in plasma samples
Measured: 6 months post-treatment
Molecular biological Disease Free Survival
Rate of patients with no detectable ctDNA
Measured: 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
Measured: 5 years last patient
Time to radiological recurrence
Time to radiological recurrence is calculated from inclusion until radiological evidence of disease recurrence
Measured: 5 years last patient
Local and distant relapse
Rate of patients with local and distant relapse
Measured: 5 years last patient
Overall survival
Time from inclusion to death from any cause
Measured: 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.
Measured: 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.
Measured: 5 years last patient
Cost-effectiveness analysis
Economic evaluation of ctDNA guided chemotherapy after curative treatment of metastatic colorectal cancer
Measured: 5 years last patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2020
- Study start25 Oct 2021
- Primary completion1 Mar 2027 (estimated)
- Study completion1 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- An open label 1:1 randomized phase II exploratory study
- Masking
- None (open label)
- Enrolment
- 350 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karen-Lise Garm Spindler
- Sponsor type
- University, hospital or other
- Collaborators
- Vejle Hospital, Zealand University Hospital
- Responsible party
- Sponsor-investigator, Karen-Lise Garm Spindler, Aarhus University Hospital
- Investigators
- Karen-Lise G Spindler, Professor, Principal investigator, Department of Oncology, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04680260
- Sponsor's protocol ID
- KFE2022
- Acronym
- OPTIMISE
- Status last verified
- Aug 2024
- First submitted
- 19 Oct 2020
- Last updated
- 14 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- OPTIMIzation of Treatment SElection and Follow up in Oligometastatic Colorectal Cancer - a ctDNA Guided Phase II Randomized Approach
- ClinicalTrials.gov ID
- NCT04680260
- Acronym / sponsor ID
- OPTIMISE / KFE2022
- Conditions
- Colorectal Cancer, Metastatic Cancer
- Keywords
- Circulating tumor DNA, Adjuvant chemotherapy, Colorectal cancer, Metastatic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- Karen-Lise Garm SpindlerUniversity, hospital or other
- Collaborators
- Vejle Hospital, Zealand University Hospital
- Study start
- 25 Oct 2021 (actual)
- Primary completion
- 1 Mar 2027 (estimated)
- Study completion
- 1 Mar 2030 (estimated)
- First posted
- 22 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- An open label 1:1 randomized phase II exploratory study
| Arm | Type | Receives |
|---|---|---|
| A: Standard of care | Active comparator | Other: Standard of careStandard decision making regarding adjuvant chemotherapy with fluoropyrimidine and oxaliplatin as per institutional standards. |
| B: ctDNA guided therapy approach | Experimental | Other: Circulating tumor DNA guided treatment approachPost ablation ctDNA results will be used for treatment decision. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard of carePatients 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. | Other | A: Standard of care |
| Circulating tumor DNA guided treatment approachCirculating 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. | Other | B: ctDNA guided therapy approach |
Primary outcome
Recurrence Free Rate
Time frame: 2 years
Rate of patients free from recurrent colorectal cancer at 2 years post local treatment
10 secondary outcomes
Toxicity of treatment
Time frame: 6 months post-treatment
Molecular biological response to therapy
Time frame: 6 months post-treatment
Molecular biological Disease Free Survival
Time frame: 1 year from inclusion
Time to molecular biological recurrence
Time frame: 5 years last patient
Time to radiological recurrence
Time frame: 5 years last patient
Local and distant relapse
Time frame: 5 years last patient
Overall survival
Time frame: 5 years last patient
Quality of life according to EORTC QLQ-CR29 and -C30
Time frame: 5 years last patient
Quality of life according to EQ-5D-5L
Time frame: 5 years last patient
Cost-effectiveness analysis
Time frame: 5 years last patient
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Karen-Lise G Spindler, Professor principal investigator
Department of Oncology, Aarhus University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Circulating tumor DNA guided treatment approach in people with Colorectal Cancer and Metastatic Cancer, run by Karen-Lise Garm Spindler at 2 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Karen-Lise G Spindler, Professor (+4591167244, k.g.spindler@rm.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence Free Rate (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2024.