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Erbitux MEtastatic Colorectal Cancer Strategy Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02484833
Recruitment Status : Completed
First Posted : June 30, 2015
Last Update Posted : March 31, 2020
Sponsor:
Information provided by (Responsible Party):
Armando Orlandi, Catholic University of the Sacred Heart

Tracking Information
First Submitted Date  ICMJE April 26, 2015
First Posted Date  ICMJE June 30, 2015
Last Update Posted Date March 31, 2020
Actual Study Start Date  ICMJE February 2015
Actual Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 25, 2015)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2015)
  • 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 ]
    RR
  • Early tumor shrinkage assessed by Response rate at week 8 [ Time Frame: at 8 weeks ]
    ETS
  • 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 ]
    OS
  • 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 ]
    Cetuximab-related skin toxicity
  • 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 ]
    Safety profile
  • 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 ]
    QoL
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Erbitux MEtastatic Colorectal Cancer Strategy Study
Official Title  ICMJE 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
Brief 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).
  • 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Antineoplastic Agents
Intervention  ICMJE
  • Drug: Cetuximab
  • Drug: FOLFIRI
Study Arms  ICMJE
  • Active Comparator: FOLFIRI + Cetuximab until disease progression
    FOLFIRI + Cetuximab until disease progression
    Interventions:
    • Drug: Cetuximab
    • Drug: FOLFIRI
  • Experimental: FOLFIRI + Cetuximab followed by Cetuximab alone
    FOLFIRI + Cetuximab for 8 cycles followed by Cetuximab alone until disease progression
    Interventions:
    • Drug: Cetuximab
    • Drug: FOLFIRI
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 29, 2020)
607
Original Estimated Enrollment  ICMJE
 (submitted: June 25, 2015)
600
Actual Study Completion Date  ICMJE March 2020
Actual Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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)
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02484833
Other Study ID Numbers  ICMJE 2014-004299-41
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Armando Orlandi, Catholic University of the Sacred Heart
Original Responsible Party Carlo Barone, Catholic University of the Sacred Heart, Clinical Professor and Head of Medical Oncology Department
Current Study Sponsor  ICMJE Armando Orlandi
Original Study Sponsor  ICMJE Carlo Barone
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Catholic University of the Sacred Heart
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP