Antineoplastic AgentsPhase 3NCT02484833
Erbitux MEtastatic Colorectal Cancer Strategy Study
A Phase 3 study testing Cetuximab and FOLFIRI in people with Antineoplastic Agents, run by Armando Orlandi at 1 site in Italy.
Trial summary
To investigate whether cetuximab alone (given until progression or cumulative toxicity) after 8 cycles of FOLFIRI + cetuximab results in a non inferior Progression Free Survival when compared with continuous FOLFIRI + cetuximab (given until progression or cumulative toxicity). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Antineoplastic Agents
- What is being tested?
- Cetuximab and FOLFIRI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 607 participants
- Where
- 1 siteItaly
- Study dates
- Feb 2015to Mar 2020
- Phase
- Phase 3
- 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
- Histologically proven diagnosis of colorectal adenocarcinoma
- Diagnosis of metastatic disease
- RAS and BRAF wildtype
- Measurable disease according to RECIST criteria v1.1
- Male or female over 18 years of age
- ECOG Performance Status 2
Show all 11Show fewer
- Life expectancy of at least 3 months
- Adequate bone marrow, liver and renal function assessed within 14 days before starting study treatment
- If female and of childbearing potential, have a negative result on a pregnancy test performed a maximum of 7 days before initiation of study treatment
- If female and of childbearing potential, or if male, agreement to use adequate contraception
- Signed informed consent obtained at screening
Who cannot join
- Any contraindication to use cetuximab, irinotecan, 5 FU or folinic acid
- Active uncontrolled infections or active disseminated intravascular coagulation
- Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix
- Pregnancy.
- Breastfeeding.
- Grade III or IV heart failure (NYHA classification)
Show all 20Show fewer
- Myocardial infarction, unstable angina pectoris, balloon angioplasty (PTCA) with or without stenting within the past 12 months before inclusion in the study
- Cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin
- Medical or psychological impairments associated with restricted ability to give consent or not allowing conduct of the study
- Previous chemotherapy for colorectal cancer with the exception of adjuvant treatment, completed at least 6 months before entering the study
- Participation in a clinical study or experimental drug treatment within 30 days prior to study inclusion or during participation in the study
- Known or clinically suspected brain metastases
- History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhoea
- Severe, non-healing wounds, ulcers or bone fractures
- Uncontrolled hypertension
- Marked proteinuria (nephrotic syndrome)
- Known DPD deficiency (specific screening not required)
- Known history of alcohol or drug abuse
- A significant concomitant disease which, in the investigating physician's opinion, rules out the patient's participation in the study
- Absent or restricted legal capacity
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Erbitux MEtastatic Colorectal Cancer Strategy Study (ERMES): A Phase III Randomized Two Arm Study With FOLFIRI + Cetuximab Until Disease Progression Compared to FOLFIRI + Cetuximab for 8 Cycles Followed by Cetuximab Alone Until Disease Progression in First Line Treatment of Patients With RAS and BRAF Wild Type Metastatic Colorectal Cancer
- To investigate whether cetuximab alone (given until progression or cumulative toxicity) after 8 cycles of FOLFIRI + cetuximab results in a non inferior Progression Free Survival when compared with continuous FOLFIRI + cetuximab (given until progression or cumulative toxicity).
- To assess whether an improvement in the incidence of grade 3-4 hematological and non-hematological adverse events (AEs) can be achieved in the experimental arm (cetuximab alone after 8 cycles FOLFIRI + cetuximab) as compared to the continuous chemotherapy arm (FOLFIRI plus cetuximab)
- To explore the possibility of using liquid biopsies for molecular profiling as well as monitoring treatment activity in mCRC pts receiving cetuximab based therapy
Read the detailed description
Survival of patients undergoing therapy with FOLFIRI + cetuximab seems to be related to the ability of this treatment to induce a rapid reduction in tumor mass. In the retrospective analyses of the FIRE-3 trial ETS was significantly associated with PFS and OS, suggesting that ETS reflects the existence of a selected population of patients highly sensitive to cetuximab. This permits the assumption that, once this goal has been achieved, further exposure to combined antineoplastic treatment (cytotoxic drugs and targeted therapy) may not result in improvement or preservation of the result, but only in an increase of side effects that will be additional to unavoidable disease progression. In addition, the heavy exposure to cytotoxic antineoplastic treatments may lead to bone marrow toxicity, hepatic and renal function decreases that could compromise the sequential treatment plan, negatively affecting OS. With the availability of an effective treatment such as cetuximab in monotherapy4 without major side effects on blood counts and liver and kidney function, the use of this treatment alone after achievement of the deepest clinical response could be a viable strategy to achieve a good control of the disease, limiting side effects. As shown in several studies designed to understand the most effective treatment sequence in colorectal carcinoma, the most important factor that influences the overall survival is the possibility to administer more lines of effective therapy. As a consequence, a de-intensifying strategy in a subgroup of highly selected RAS and BRAF WT population might segregate a group of patients with the largest potential for fast-primary treatment. Joining the best induction treatment with the expression of patients capability to undergo additional lines of antineoplastic therapy may be the way to optimize the continuum of care.
Recently, several mechanisms of resistance to anti-EGFR therapy have been described, but until now none may used early in order to support the treatment choice.Moreover, assessment of secondary resistance requires further tissue samples and often it is not really feasible. Therefore, a prospective multiple gene mutation analysis could meet the need of characterizing primary resistance, whereas liquid biopsy might help to recognize resistance occurring early during treatment by means of a simple and repeatable assay. Based on all these considerations, the investigators designed a strategy study: a phase III randomized two arm study with FOLFIRI + cetuximab until disease progression compared to FOLFIRI + cetuximab for 8 cycles followed by cetuximab alone until disease progression in the first line treatment of patients with RAS and BRAF WT metastatic colorectal cancer combined with a prospective multiple gene mutation analysis of both tumor tissue and blood.
- Conditions
- Antineoplastic Agents
- Being tested
- Cetuximab, FOLFIRI
- Keywords
- First line, metastatic colorectal cancer, Cetuximab, strategy study
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
FOLFIRIDrug
| Study group | Role | What they receive |
|---|---|---|
| FOLFIRI + Cetuximab until disease progression | Active comparator | FOLFIRI + Cetuximab until disease progression Receives: Drug: Cetuximab; Drug: FOLFIRI |
| FOLFIRI + Cetuximab followed by Cetuximab alone | Experimental | FOLFIRI + Cetuximab for 8 cycles followed by Cetuximab alone until disease progression Receives: Drug: Cetuximab; Drug: FOLFIRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
PFS
Measured: every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Incidence of grade 3-4 AEs
AEs
Measured: weekly from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Secondary outcomes (6)
Response rate
RR
Measured: every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Early tumor shrinkage assessed by Response rate at week 8
ETS
Measured: at 8 weeks
Overall survival
OS
Measured: every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Cetuximab-related skin toxicity by CTCAE
Cetuximab-related skin toxicity
Measured: weekly from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Safety profile assessed by CTCAE
Safety profile
Measured: weekly until from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Quality of life assessed by EORT QLQ-C30 and DLQI questionnaires
QoL
Measured: every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 32 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2015 (estimated)
- Study startFeb 2015
- Primary completionDec 2019
- Study completionMar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Antineoplastic AgentsStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 607 participants (actual)
Sponsor and investigators
- Lead sponsor
- Armando Orlandi
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Armando Orlandi, Catholic University of the Sacred Heart
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02484833
- Sponsor's protocol ID
- 2014-004299-41
- Other IDs
- 2014
- Status last verified
- Mar 2020
- First submitted
- 26 Apr 2015
- Last updated
- 31 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Pinto C, Orlandi A, Normanno N, Maiello E, Calegari MA, Antonuzzo L, Bordonaro R, Zampino MG, Pini S, Bergamo F, Tonini G, Avallone A, Latiano TP, Rosati G, Cogoni AA, Ballestrero A, Zaniboni A, Roselli M, Tamberi S, Barone C. Fluorouracil, Leucovorin, and Irinotecan Plus Cetuximab Versus Cetuximab as Maintenance Therapy in First-Line Therapy for RAS and BRAF Wild-Type Metastatic Colorectal Cancer: Phase III ERMES Study. J Clin Oncol. 2024 Apr 10;42(11):1278-1287. doi: 10.1200/JCO.23.01021. Epub 2024 Jan 5.
PubMed 38181312
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Erbitux MEtastatic Colorectal Cancer Strategy Study (ERMES): A Phase III Randomized Two Arm Study With FOLFIRI + Cetuximab Until Disease Progression Compared to FOLFIRI + Cetuximab for 8 Cycles Followed by Cetuximab Alone Until Disease Progression in First Line Treatment of Patients With RAS and BRAF Wild Type Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT02484833
- Acronym / sponsor ID
- 2014-004299-41
- Conditions
- Antineoplastic Agents
- Keywords
- First line, metastatic colorectal cancer, Cetuximab, strategy study
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 607 participants (actual)
- Lead sponsor
- Armando OrlandiUniversity, hospital or other
- Study start
- Feb 2015 (actual)
- Primary completion
- Dec 2019 (actual)
- Study completion
- Mar 2020 (actual)
- First posted
- 30 Jun 2015 (estimated)
- 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.
- To investigate whether cetuximab alone (given until progression or cumulative toxicity) after 8 cycles of FOLFIRI + cetuximab results in a non inferior Progression Free Survival when compared with continuous FOLFIRI + cetuximab (given until progression or cumulative toxicity).
- To assess whether an improvement in the incidence of grade 3-4 hematological and non-hematological adverse events (AEs) can be achieved in the experimental arm (cetuximab alone after 8 cycles FOLFIRI + cetuximab) as compared to the continuous chemotherapy arm (FOLFIRI plus cetuximab)
- To explore the possibility of using liquid biopsies for molecular profiling as well as monitoring treatment activity in mCRC pts receiving cetuximab based therapy
Detailed description
Survival of patients undergoing therapy with FOLFIRI + cetuximab seems to be related to the ability of this treatment to induce a rapid reduction in tumor mass. In the retrospective analyses of the FIRE-3 trial ETS was significantly associated with PFS and OS, suggesting that ETS reflects the existence of a selected population of patients highly sensitive to cetuximab. This permits the assumption that, once this goal has been achieved, further exposure to combined antineoplastic treatment (cytotoxic drugs and targeted therapy) may not result in improvement or preservation of the result, but only in an increase of side effects that will be additional to unavoidable disease progression. In addition, the heavy exposure to cytotoxic antineoplastic treatments may lead to bone marrow toxicity, hepatic and renal function decreases that could compromise the sequential treatment plan, negatively affecting OS. With the availability of an effective treatment such as cetuximab in monotherapy4 without major side effects on blood counts and liver and kidney function, the use of this treatment alone after achievement of the deepest clinical response could be a viable strategy to achieve a good control of the disease, limiting side effects. As shown in several studies designed to understand the most effective treatment sequence in colorectal carcinoma, the most important factor that influences the overall survival is the possibility to administer more lines of effective therapy. As a consequence, a de-intensifying strategy in a subgroup of highly selected RAS and BRAF WT population might segregate a group of patients with the largest potential for fast-primary treatment. Joining the best induction treatment with the expression of patients capability to undergo additional lines of antineoplastic therapy may be the way to optimize the continuum of care.
Recently, several mechanisms of resistance to anti-EGFR therapy have been described, but until now none may used early in order to support the treatment choice.Moreover, assessment of secondary resistance requires further tissue samples and often it is not really feasible. Therefore, a prospective multiple gene mutation analysis could meet the need of characterizing primary resistance, whereas liquid biopsy might help to recognize resistance occurring early during treatment by means of a simple and repeatable assay. Based on all these considerations, the investigators designed a strategy study: a phase III randomized two arm study with FOLFIRI + cetuximab until disease progression compared to FOLFIRI + cetuximab for 8 cycles followed by cetuximab alone until disease progression in the first line treatment of patients with RAS and BRAF WT metastatic colorectal cancer combined with a prospective multiple gene mutation analysis of both tumor tissue and blood.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FOLFIRI + Cetuximab until disease progression | Active comparator | Drug: Cetuximab, Drug: FOLFIRIFOLFIRI + Cetuximab until disease progression |
| FOLFIRI + Cetuximab followed by Cetuximab alone | Experimental | Drug: Cetuximab, Drug: FOLFIRIFOLFIRI + Cetuximab for 8 cycles followed by Cetuximab alone until disease progression |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically proven diagnosis of colorectal adenocarcinoma
- Diagnosis of metastatic disease
- RAS and BRAF wildtype
- Measurable disease according to RECIST criteria v1.1
- Male or female over 18 years of age
Key exclusion criteria (20 listed)
- Any contraindication to use cetuximab, irinotecan, 5 FU or folinic acid
- Active uncontrolled infections or active disseminated intravascular coagulation
- Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix
- Pregnancy.
- Breastfeeding.
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 |
|---|---|---|
| Cetuximab | Drug | FOLFIRI + Cetuximab followed by Cetuximab alone, FOLFIRI + Cetuximab until disease progression |
| FOLFIRI | Drug | FOLFIRI + Cetuximab followed by Cetuximab alone, FOLFIRI + Cetuximab until disease progression |
Primary outcome
Progression-free survival
Time frame: every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
PFS
Incidence of grade 3-4 AEs
Time frame: weekly from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
AEs
6 secondary outcomes
Response rate
Time frame: every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Early tumor shrinkage assessed by Response rate at week 8
Time frame: at 8 weeks
Overall survival
Time frame: every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Cetuximab-related skin toxicity by CTCAE
Time frame: weekly from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Safety profile assessed by CTCAE
Time frame: weekly until from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Quality of life assessed by EORT QLQ-C30 and DLQI questionnaires
Time frame: every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 32 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2020.
- Derived from this study: PubMed 38181312Pinto C, Orlandi A, Normanno N, Maiello E, Calegari MA, Antonuzzo L, Bordonaro R, Zampino MG, Pini S, Bergamo F, Tonini G, Avallone A, Latiano TP, Rosati G, Cogoni AA, Ballestrero A, Zaniboni A, Roselli M, Tamberi S, Barone C. Fluorouracil, Leucovorin, and Irinotecan Plus Cetuximab Versus Cetuximab as Maintenance Therapy in First-Line Therapy for RAS and BRAF Wild-Type Metastatic Colorectal Cancer: Phase III ERMES Study. J Clin Oncol. 2024 Apr 10;42(11):1278-1287. doi: 10.1200/JCO.23.01021. Epub 2024 Jan 5.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Cetuximab and FOLFIRI in people with Antineoplastic Agents, run by Armando Orlandi at 1 site in Italy.
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 11 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: finished, as of the sponsor's last update on 31 Mar 2020. 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 Italy. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (time frame: every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02484833, which also lists 1 linked publication.
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 31 Mar 2020; AzTrials last refreshed its copy on 2 Nov 2026.