Metastatic Colon CancerPhase 3DIAMONDNCT06446557
De-scalation or swItch of Treatment According to Circulating tuMOr DNA Variation After 2 Cycles of Doublet Chemotherapy Plus Targeted Agent in Metastatic Unresectable Colorectal Cancer
A Phase 3 study testing treatment adaptation guided by ctDNA variation and standard management in people with Metastatic Colon Cancer, run by University Hospital, Rouen at 1 site in France.
Trial summary
Background : In unresectable mCRC, a de-escalation strategy using maintenance or chemotherapy (CT) discontinuation in selected cases is considered as a valid option in non-progressive patients after a first-line induction of doublet CT + targeted agent (TA) (1-7). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colon Cancer
- What is being tested?
- treatment adaptation guided by ctDNA variation and standard management
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 408 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2026to 1 Jun 2032
- Phase
- Phase 3
- 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
- Histologically proven diagnosis of RAS WT or mutant, MSS, BRAFV600E non-mutated colorectal cancer.
- Left side or rectal cancer
- An unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease.
- At least one measurable lesion according to RECIST criteria version 1.1.
- Age ≥ 18 years.
- ECOG PS ≤ 1
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- Neutrophils ≥ 1.5 x 10^9/L, Platelets ≥ 100 x 10^9/L, Hb > 9 g/dl.
- Total bilirubin ≤ 1.5 time the upper-normal limits (UNL) and ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 x UNL, or 5 x UNL in case of liver metastases, alkaline phosphatase ≤ 2.5 x UNL, or 5 x UNL in case of liver metastases.
- Creatinine clearance > 50 mL/min or serum creatinine ≤ 1.5 x UNL.
- The patient's urinary protein is ≤ 1+ on dipstick or routine urinalysis.
- Adequate coagulation function [International Normalized Ratio (INR) ≤1.5 and Partial. Thromboplastin Time (PTT) or activated PTT (aPTT) ≤1.5 x ULN.
- Written informed consent.
Who cannot join
- Right side colon cancer
- First-line chemotherapy +/- biologic agents for mCRC before C1
- Radiotherapy to any site within 4 weeks before C1
- Adjuvant oxaliplatin-based treatment completed less than 6 months before relapse.
- Treatment with any investigational drug within 30 days prior to C1
- Known allergy to any of the study treatment components.
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- Dihydropyrimidine dehydrogenase (DPD) deficiency.
- Documented and/or symptomatic brain or leptomeningeal metastases.
- Patient with active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thrombotic or hemorrhagic disorder, or any other serious uncontrolled medical disorders in the opinion of the investigator.
- Uncontrolled or poorly controlled hypertension despite standard medical management.
- Severe renal or hepatic failure
- Serious or non-healing wound, ulcer, or bone fracture within 28 days prior to C1
- Other co-existing malignancies or malignancies diagnosed within the last 3 years with the exception of basal and squamous cell carcinoma or cervical cancer in situ.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start.
- Infection with the human immunodeficiency virus.
- Symptomatic peripheral neuropathy grade 1 according the NCI CTC.
- Acute or subacute bowel obstruction or history of chronic diarrhea, which is considered clinically significant in the opinion of the investigator.
- Chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted.
- Pregnant or lactating women.
- Patient with active psychiatric illness or social situation that would severely limit compliance with study requirements.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site
CHU de ROUEN
Rouen, 76031
Frédéric Di Fiore, Pr, 232886456 ext. +33, Frederic.di-fiore@chu-rouen.fr
Frédéric Di Fiore, Pr
About this study
Official title: De-scalation or swItch of Treatment According to Circulating tuMOr DNA Variation After 2 Cycles of Doublet Chemotherapy Plus Targeted Agent in Metastatic Unresectable Colorectal Cancer (DIAMOND Study): A Randomized Phase III of PRODIGE Intergroup
Background : In unresectable mCRC, a de-escalation strategy using maintenance or chemotherapy (CT) discontinuation in selected cases is considered as a valid option in non-progressive patients after a first-line induction of doublet CT + targeted agent (TA) (1-7).
In this context, circulating tumor DNA (ctDNA) is considered very promising to optimize decision making. Indeed, ctDNA harbour the same main alterations of the tumor and has been recognized as biologically relevant to reflect tumor dynamics and therapeutic efficacy (8).
Read more
As reported in mCRC, that early variation of ctDNA during CT may be relevant to predict outcome (9-11). Indeed, patients with a ctDNA decrease from the first (C1) to the third (C3) cycles of CT (∆≥80% or ctDNA<0.1 ng/ml at C3) or without ctDNA detectable at C1 and C3 have significant better survival as compared to patients with less decrease or with ctDNA increase (10). ctDNA monitoring had never been prospectively evaluated to guide early adaptation in the treatment strategy in mCRC.
Aim: A randomized phase III, open label, strategy trial of the superiority in overall survival (OS) adjusted on quality of life of an early treatment adaptation guided by ctDNA variation versus a standard management in unresectable left-side, MSS-BRAFV600E non-mutated mCRC treated by first-line doublet CT + TA.
Patients and methods :
-Main inclusion criteria will be (i) unresectable left-side and non-pre-treated mCRC (ii) MSS and non-mutated BRAFV600E tumor (iii) at least one measurable lesion (iv) ECOG 0-1 and adequate biological functions for first-line doublet CT + TA (antiEGFR if RAS WT, bevacizumab (BV) if RAS MUT).
Randomization (1:1) between an experimental strategy guided by ctDNA variation with de-escalation (Arm A1 or A2) or switch of treatment (Arm A3) versus standard strategy (Arm B). The analysis of variation of ctDNA from C1-C3 will be centralized and detected using Digital PCR targeting hypermethylation of WIF1/NPY genes (10) in real-time in arm A and in second step in arm B.
Randomization in Arm A: after 4 cycles of doublet + TA, non-progressive patients will be allocated to a strategy according to ctDNA value and variation from C1-C3:
Arm A1: CT discontinuation (ctDNA normalization < 0.1 ng/ml or ctDNA not detectable) Arm A2 : maintenance with fluoropyrimidine + TA (ctDNA ≥ 0.1 ng/ml and ∆ctDNA≥ 80%).
Arm A3 : ctDNA non-responders (∆ctDNA < 80% or increase) : switch of CT +/- TA.
Randomisation in Arm B: at least 8 cycles of doublet CT + TA before adaptation of sequence at physician choice.
Statistical considerations : with an expected median OS at 32 months (mean 37.6 months), a mean QoL at 70.0% in first-line mCRC, corresponding to 0.700 x 37.6 = 26.3 QALM or 2.19 QALY (SD 1.18 QALY), 408 patients are required (randomization 1:1) to show a gain of 4 months of quality-adjusted OS (4 QALM or 0.33 QALY) in experimental ctDNA strategy versus standard strategy (5% two-sided type I error rate, 81% power and 1.18 QALY SD).
The secondary objectives will be:
- To compare strategies (standard vs ctDNA guided) overall and in the subgroups of ctDNA response on 18, 24 and 36-months restricted mean of QoL-adjusted OS, OS, PFS, response rate, toxicity, Quality of Life and cost utility.
- Bio-collection for further ctDNA analysis. Only cost of samples collection and their transportation to the resource center is requested. Further ancillary analysis will be subject to independent funding requests to evaluate :
- ctDNA kinetics during the induction and its impact on outcome in overall population and in each arm
- ctDNA changes between time points during de-escalation arms to determine thresholds of variations predictive of clinical and/or radiological progression.
Conclusion: DIAMOND is a randomized phase III strategy trial to show the superiority in OS adjusted on quality of life of an early treatment adaptation guided by ctDNA versus a standard management in unresectable left-side, MSS-BRAFV600E non-mutated mCRC treated by first-line doublet CT + TA.
- Conditions
- Metastatic Colon Cancer
- Being tested
- treatment adaptation guided by ctDNA variation, standard management
- Medical subject headings
- Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
treatment adaptation guided by ctDNA variationDrug
after 4 cycles of doublet + TA, non-progressive patients will be allocated to a strategy according to ctDNA value and variation from C1-C3: Arm A1: CT discontinuation (ctDNA normalization < 0.1 ng/ml or ctDNA not detectable) Arm A2 : maintenance with fluoropyrimidine + TA (ctDNA ≥ 0.1 ng/ml and ∆ctDNA≥ 80%).
Arm A3 : ctDNA non-responders (∆ctDNA < 80% or increase) : switch of CT +/- TA.
standard managementDrug
At least 8 cycles of doublet CT + TA before adaptation of sequence at physician choice.
| Study group | Role | What they receive |
|---|---|---|
| ctDNA Arm | Experimental | After 4 cycles of doublet + TA, non-progressive patients will be allocated to a strategy according to ctDNA value and variation from C1-C3 Receives: Drug: treatment adaptation guided by ctDNA variation |
| Control Arm | Active comparator | At least 8 cycles of doublet CT + TA before adaptation of sequence at physician choice. Receives: Drug: standard management |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the superiority in quality-adjusted OS of an early treatment adaptation guided by ctDNA variation
The primary endpoint is the superiority in overall survival (OS) adjusted on quality-adjusted life years (QALYs) for the experimental arm guided by ctDNA (Arm A1 + A2 + A3) as compared to the standard management (Arm B).
The follow-up will start from the date of randomization. Patients alive at last follow-up will have an extrapolation of their QALY, based on the OS curve and the patient QoL at last follow-up.
Measured: through study completion, an average of 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2024
- Study startJun 2026 (estimated)
- Primary completion1 Jun 2032 (estimated)
- Study completion1 Jun 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colon CancerStudies of the same condition, open and under way.
- More trials run by University Hospital, RouenThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 408 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06446557
- Sponsor's protocol ID
- 2022/0343/HP
- Acronym
- DIAMOND
- Status last verified
- Feb 2026
- First submitted
- 26 Feb 2024
- Last updated
- 9 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- De-scalation or swItch of Treatment According to Circulating tuMOr DNA Variation After 2 Cycles of Doublet Chemotherapy Plus Targeted Agent in Metastatic Unresectable Colorectal Cancer (DIAMOND Study): A Randomized Phase III of PRODIGE Intergroup
- ClinicalTrials.gov ID
- NCT06446557
- Acronym / sponsor ID
- DIAMOND / 2022/0343/HP
- Conditions
- Metastatic Colon Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 408 participants (estimated)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Study start
- Jun 2026 (estimated)
- Primary completion
- 1 Jun 2032 (estimated)
- Study completion
- 1 Jun 2032 (estimated)
- First posted
- 6 Jun 2024 (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.
Background : In unresectable mCRC, a de-escalation strategy using maintenance or chemotherapy (CT) discontinuation in selected cases is considered as a valid option in non-progressive patients after a first-line induction of doublet CT + targeted agent (TA) (1-7).
In this context, circulating tumor DNA (ctDNA) is considered very promising to optimize decision making. Indeed, ctDNA harbour the same main alterations of the tumor and has been recognized as biologically relevant to reflect tumor dynamics and therapeutic efficacy (8).
As reported in mCRC, that early variation of ctDNA during CT may be relevant to predict outcome (9-11). Indeed, patients with a ctDNA decrease from the first (C1) to the third (C3) cycles of CT (∆≥80% or ctDNA<0.1 ng/ml at C3) or without ctDNA detectable at C1 and C3 have significant better survival as compared to patients with less decrease or with ctDNA increase (10). ctDNA monitoring had never been prospectively evaluated to guide early adaptation in the treatment strategy in mCRC.
Aim: A randomized phase III, open label, strategy trial of the superiority in overall survival (OS) adjusted on quality of life of an early treatment adaptation guided by ctDNA variation versus a standard management in unresectable left-side, MSS-BRAFV600E non-mutated mCRC treated by first-line doublet CT + TA.
Patients and methods :
-Main inclusion criteria will be (i) unresectable left-side and non-pre-treated mCRC (ii) MSS and non-mutated BRAFV600E tumor (iii) at least one measurable lesion (iv) ECOG 0-1 and adequate biological functions for first-line doublet CT + TA (antiEGFR if RAS WT, bevacizumab (BV) if RAS MUT).
Randomization (1:1) between an experimental strategy guided by ctDNA variation with de-escalation (Arm A1 or A2) or switch of treatment (Arm A3) versus standard strategy (Arm B). The analysis of variation of ctDNA from C1-C3 will be centralized and detected using Digital PCR targeting hypermethylation of WIF1/NPY genes (10) in real-time in arm A and in second step in arm B.
Randomization in Arm A: after 4 cycles of doublet + TA, non-progressive patients will be allocated to a strategy according to ctDNA value and variation from C1-C3:
Arm A1: CT discontinuation (ctDNA normalization < 0.1 ng/ml or ctDNA not detectable) Arm A2 : maintenance with fluoropyrimidine + TA (ctDNA ≥ 0.1 ng/ml and ∆ctDNA≥ 80%).
Arm A3 : ctDNA non-responders (∆ctDNA < 80% or increase) : switch of CT +/- TA.
Randomisation in Arm B: at least 8 cycles of doublet CT + TA before adaptation of sequence at physician choice.
Statistical considerations : with an expected median OS at 32 months (mean 37.6 months), a mean QoL at 70.0% in first-line mCRC, corresponding to 0.700 x 37.6 = 26.3 QALM or 2.19 QALY (SD 1.18 QALY), 408 patients are required (randomization 1:1) to show a gain of 4 months of quality-adjusted OS (4 QALM or 0.33 QALY) in experimental ctDNA strategy versus standard strategy (5% two-sided type I error rate, 81% power and 1.18 QALY SD).
The secondary objectives will be:
- To compare strategies (standard vs ctDNA guided) overall and in the subgroups of ctDNA response on 18, 24 and 36-months restricted mean of QoL-adjusted OS, OS, PFS, response rate, toxicity, Quality of Life and cost utility.
- Bio-collection for further ctDNA analysis. Only cost of samples collection and their transportation to the resource center is requested. Further ancillary analysis will be subject to independent funding requests to evaluate :
- ctDNA kinetics during the induction and its impact on outcome in overall population and in each arm
- ctDNA changes between time points during de-escalation arms to determine thresholds of variations predictive of clinical and/or radiological progression.
Conclusion: DIAMOND is a randomized phase III strategy trial to show the superiority in OS adjusted on quality of life of an early treatment adaptation guided by ctDNA versus a standard management in unresectable left-side, MSS-BRAFV600E non-mutated mCRC treated by first-line doublet CT + TA.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ctDNA Arm | Experimental | Drug: treatment adaptation guided by ctDNA variationAfter 4 cycles of doublet + TA, non-progressive patients will be allocated to a strategy according to ctDNA value and variation from C1-C3 |
| Control Arm | Active comparator | Drug: standard managementAt least 8 cycles of doublet CT + TA before adaptation of sequence at physician choice. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically proven diagnosis of RAS WT or mutant, MSS, BRAFV600E non-mutated colorectal cancer.
- Left side or rectal cancer
- An unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease.
- At least one measurable lesion according to RECIST criteria version 1.1.
- Age ≥ 18 years.
Key exclusion criteria (20 listed)
- Right side colon cancer
- First-line chemotherapy +/- biologic agents for mCRC before C1
- Radiotherapy to any site within 4 weeks before C1
- Adjuvant oxaliplatin-based treatment completed less than 6 months before relapse.
- Treatment with any investigational drug within 30 days prior to C1
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 |
|---|---|---|
| treatment adaptation guided by ctDNA variationafter 4 cycles of doublet + TA, non-progressive patients will be allocated to a strategy according to ctDNA value and variation from C1-C3: Arm A1: CT discontinuation (ctDNA normalization < 0.1 ng/ml or ctDNA not detectable) Arm A2 : maintenance with fluoropyrimidine + TA (ctDNA ≥ 0.1 ng/ml and ∆ctDNA≥ 80%). Arm A3 : ctDNA non-responders (∆ctDNA < 80% or increase) : switch of CT +/- TA. | Drug | ctDNA Arm |
| standard managementAt least 8 cycles of doublet CT + TA before adaptation of sequence at physician choice. | Drug | Control Arm |
Primary outcome
Evaluate the superiority in quality-adjusted OS of an early treatment adaptation guided by ctDNA variation
Time frame: through study completion, an average of 7 years
The primary endpoint is the superiority in overall survival (OS) adjusted on quality-adjusted life years (QALYs) for the experimental arm guided by ctDNA (Arm A1 + A2 + A3) as compared to the standard management (Arm B). The follow-up will start from the date of randomization. Patients alive at last follow-up will have an extrapolation of their QALY, based on the OS curve and the patient QoL at last follow-up.
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 9 Jun 2026.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing treatment adaptation guided by ctDNA variation and standard management in people with Metastatic Colon Cancer, run by University Hospital, Rouen at 1 site in France.
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 12 inclusion and 20 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: opening soon, as of the sponsor's last update on 9 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Frédéric Di Fiore, Pr (232886456 ext. +33, Frederic.di-fiore@chu-rouen.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the superiority in quality-adjusted OS of an early treatment adaptation guided by ctDNA variation (time frame: through study completion, an average of 7 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 9 Jun 2026; AzTrials last refreshed its copy on 7 Nov 2026.