Colorectal CancerPhase 2IMPROVE-ITNCT03748680
IMPROVE Intervention Trial Implementing Non-invasive Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer
A Phase 2 study testing Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapy and Intensified Follow-up Schedule in people with Colorectal Cancer and Circulating Tumor DNA, run by Karen-Lise Garm Spindler at 4 sites in Denmark.
Trial summary
A open label 1:1 randomized phase II exploratory study investigating adjuvant therapy in patients with molecular biologically detectable residual disease after primary resection for localized colorectal tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Circulating Tumor DNA, Adjuvant Chemotherapy
- What is being tested?
- Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapy and Intensified Follow-up Schedule
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 4 sitesDenmark
- Study dates
- 1 Oct 2018to 1 Oct 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Surgically removed Adenocarcinoma of the colon or rectum
- Pathologically stage I or II disease, and radical resection
- Detectable ctDNA in two weeks postoperative plasma sample
- No indication for adjuvant chemotherapy according to DCCG guidelines (website)
- Age at least 18 years
- ECOG performance status 0-2
Show all 10Show fewer
- Clinically eligible for adjuvant chemotherapy 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 and abdomen
- Incapacity, frailty, disability and comorbidity to a degree that according to the investigator is not compatible with combination chemotherapy
- Previous treatment with 5FU or oxaliplatin
- Neuropathy NCI 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
Trial locations and contacts
4 sites in 1 country.
Denmark4 sites, 4 recruiting
- Recruiting
Aalborg University Hospital
Aalborg
- Recruiting
Aarhus University Hospital
Aarhus, 8000
Karen-Lise G Spindler, Prof., +457846 2535, k.g.spindler@rm.dk
Line M Sparvath, CRN, 457846 2610, linspa@rm.dk
- Recruiting
Herlev Hospital
Herlev
- Recruiting
Odense University Hospital
Odense
About this study
Official title: Implementing Non-invasive Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer
A open label 1:1 randomized phase II exploratory study investigating adjuvant therapy in patients with molecular biologically detectable residual disease after primary resection for localized colorectal tumors.
Read the detailed description
The main clinical hypothesis is that patients having undergone radical resection from CRC do not present with detectable tumor DNA in the plasma, whereas patients with detectable tumor DNA two weeks' post surgery have residual microscopic disease, and consequently a high risk of diseases recurrence which can be prevented with adjuvant chemotherapy.
The primary aim of the present study is to investigate - in a randomized trial - if use of standard adjuvant chemotherapy therapy improves the disease free survival in patients with molecular biological residual disease where adjuvant chemotherapy is not standard treatment .
Secondary aims include investigating molecular biological response to adjuvant chemotherapy in patients with post-operative ctDNA.
- Conditions
- Colorectal Cancer, Circulating Tumor DNA, Adjuvant Chemotherapy, Progression Free Survival
- Being tested
- Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapy, Intensified Follow-up Schedule
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapyDrug
Six months of adjuvant combination chemotherapy with Capox (or FOLFOX) Patients will receive adjuvant chemotherapy with eight cycles of CAPOX (oxaliplatin 130 mg/m2 day 1 and capecitabine 1000 mg/m2 b.i.d. days 1-14, repeated every 3 weeks.
(Patients with an ileostomy are only eligible for FOLFOX and will be treated with 12 cycles of FOLFOX (oxaliplatin 85 mg/m2 day 1, leucovorin 400 mg/m2 day 1, 5FU 400 mg/m2 bolus day 1 and 5FU 2400 mg/ m2 over 46-48 hours day 1-3, repeated every second weeks)
Intensified Follow-up ScheduleOther
Close monitoring with Imaging during follow-up Patients included in this trial will undergo intensified follow-up with CT-chest and abdomen every four months after surgery for the first 2 years, then every 6 months for 1 years and finally once yearly for the last 2 years up to 5 years follow-up is completed.
| Study group | Role | What they receive |
|---|---|---|
| A | Active comparator | Intensified follow-up schedule Receives: Other: Intensified Follow-up Schedule |
| B | Experimental | Adjuvant chemotherapy + intensified follow-up schedule Receives: Drug: Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
DFS
Disease free survival
Measured: 3 years
Secondary outcomes (8)
Molecular biological response
Molecular biological response at 6 months
Measured: 6 months
MB-DFS
Molecular biological disease free survival at 1 year
Measured: 1 year
TT-MBR
Time to molecular biological recurrence
Measured: 3 years
TTR
Time to radiological recurrence
Measured: 3 years
LRR
Local recurrence rate
Measured: 3 years
DRR
Distant recurrence rate
Measured: 3 years
OS
Overall survival
Measured: 5 years
TR
Translational research exploratory
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2018
- Study start1 Oct 2018
- Primary completion1 Oct 2023 (estimated)
- Study completion1 Oct 2025 (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
- A open label 1:1 randomized phase II exploratory study
- Masking
- None (open label)
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karen-Lise Garm Spindler
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Karen-Lise Garm Spindler, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03748680
- Sponsor's protocol ID
- KFE-1803
- Acronym
- IMPROVE-IT
- Status last verified
- Feb 2022
- First submitted
- 19 Nov 2018
- Last updated
- 25 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Implementing Non-invasive Circulating Tumor DNA Analysis to Optimize the Operative and Postoperative Treatment for Patients With Colorectal Cancer
- ClinicalTrials.gov ID
- NCT03748680
- Acronym / sponsor ID
- IMPROVE-IT / KFE-1803
- Conditions
- Colorectal Cancer, Circulating Tumor DNA, Adjuvant Chemotherapy, Progression Free Survival
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- Karen-Lise Garm SpindlerUniversity, hospital or other
- Study start
- 1 Oct 2018 (actual)
- Primary completion
- 1 Oct 2023 (estimated)
- Study completion
- 1 Oct 2025 (estimated)
- First posted
- 21 Nov 2018 (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 open label 1:1 randomized phase II exploratory study investigating adjuvant therapy in patients with molecular biologically detectable residual disease after primary resection for localized colorectal tumors.
Detailed description
The main clinical hypothesis is that patients having undergone radical resection from CRC do not present with detectable tumor DNA in the plasma, whereas patients with detectable tumor DNA two weeks' post surgery have residual microscopic disease, and consequently a high risk of diseases recurrence which can be prevented with adjuvant chemotherapy.
The primary aim of the present study is to investigate - in a randomized trial - if use of standard adjuvant chemotherapy therapy improves the disease free survival in patients with molecular biological residual disease where adjuvant chemotherapy is not standard treatment .
Secondary aims include investigating molecular biological response to adjuvant chemotherapy in patients with post-operative ctDNA.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A open label 1:1 randomized phase II exploratory study
| Arm | Type | Receives |
|---|---|---|
| A | Active comparator | Other: Intensified Follow-up ScheduleIntensified follow-up schedule |
| B | Experimental | Drug: Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapyAdjuvant chemotherapy + intensified follow-up schedule |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Surgically removed Adenocarcinoma of the colon or rectum
- Pathologically stage I or II disease, and radical resection
- Detectable ctDNA in two weeks postoperative plasma sample
- No indication for adjuvant chemotherapy according to DCCG guidelines (website)
- Age at least 18 years
Key exclusion criteria (6 listed)
- Radiological evidence of distant metastasis, by CT- chest and abdomen
- Incapacity, frailty, disability and comorbidity to a degree that according to the investigator is not compatible with combination chemotherapy
- Previous treatment with 5FU or oxaliplatin
- Neuropathy NCI grade > 1
- Other malignant tumor within 5 years except non-melanoma skin cancer or carcinoma in situ cervicis uteri
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 |
|---|---|---|
| Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapySix months of adjuvant combination chemotherapy with Capox (or FOLFOX) Patients will receive adjuvant chemotherapy with eight cycles of CAPOX (oxaliplatin 130 mg/m2 day 1 and capecitabine 1000 mg/m2 b.i.d. days 1-14, repeated every 3 weeks. (Patients with an ileostomy are only eligible for FOLFOX and will be treated with 12 cycles of FOLFOX (oxaliplatin 85 mg/m2 day 1, leucovorin 400 mg/m2 day 1, 5FU 400 mg/m2 bolus day 1 and 5FU 2400 mg/ m2 over 46-48 hours day 1-3, repeated every second weeks) | Drug | B |
| Intensified Follow-up ScheduleClose monitoring with Imaging during follow-up Patients included in this trial will undergo intensified follow-up with CT-chest and abdomen every four months after surgery for the first 2 years, then every 6 months for 1 years and finally once yearly for the last 2 years up to 5 years follow-up is completed. | Other | A |
Primary outcome
DFS
Time frame: 3 years
Disease free survival
8 secondary outcomes
Molecular biological response
Time frame: 6 months
MB-DFS
Time frame: 1 year
TT-MBR
Time frame: 3 years
TTR
Time frame: 3 years
LRR
Time frame: 3 years
DRR
Time frame: 3 years
OS
Time frame: 5 years
TR
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2022.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
4 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 Capox (or FOLFOX) including flouropyrimidine and oxaliplatin combination chemotherapy and Intensified Follow-up Schedule in people with Colorectal Cancer and Circulating Tumor DNA, run by Karen-Lise Garm Spindler at 4 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 10 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: status not confirmed, as of the sponsor's last update on 25 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Karen-Lise G Spindler, Professor (0045 7846 2535 ext. +4578462535, 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?
DFS (time frame: 3 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 25 Feb 2022.