Clinical Trials /

MoLiMoR - A Study With FOLFIRI-based First-line Therapy With or Without Intermittent Cetuximab

NCT04554836

Description:

This is an open-label, prospective, randomized, multicenter phase II trial that will evaluate the efficacy and safety of intermittent addition of cetuximab to a FOLFIRI-based first line therapy to patients with RAS (Rat sarcoma)-mutant mCRC (Metastatic colorectal cancer) diagnosis who convert to RAS wild-type using monitoring of the RAS mutation status by liquid biopsy.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: MoLiMoR - A Study With FOLFIRI-based First-line Therapy With or Without Intermittent Cetuximab
  • Official Title: Modulation of the FOLFIRI-based Standard First-line Therapy With Cetuximab, Controlled by Monitoring the RAS (Rat Sarcoma) Mutation Load by Liquid Biopsy in RAS-mutated mCRC (Metastatic Colorectal Cancer): A Randomized Phase II Study With FOLFIRI-based First-line Therapy With or Without Intermittent Cetuximab (MoLiMoR)

Clinical Trial IDs

  • ORG STUDY ID: 4213000
  • NCT ID: NCT04554836

Conditions

  • Adenocarcinoma of the Colon
  • Adenocarcinoma of the Rectum

Interventions

DrugSynonymsArms
CetuximabFOLFIRI + cetuximab

Purpose

This is an open-label, prospective, randomized, multicenter phase II trial that will evaluate the efficacy and safety of intermittent addition of cetuximab to a FOLFIRI-based first line therapy to patients with RAS (Rat sarcoma)-mutant mCRC (Metastatic colorectal cancer) diagnosis who convert to RAS wild-type using monitoring of the RAS mutation status by liquid biopsy.

Trial Arms

NameTypeDescriptionInterventions
FOLFIRI + cetuximabExperimentalPatients in Arm A will receive FOLFIRI + cetuximab until progressive disease (PD), unacceptable toxicity, withdrawal of informed consent or death, whatever occurs first. The recurrence of RAS-mutation without PD to switch back to FOLFIRI. In case of repeated conversion to RAS wild-type without PD, treatment will shift to FOLFIRI + cetuximab again, and so on. Switches of treatment will proceed until progressive disease (PD), unacceptable toxicity, withdrawal of informed consent or death, whatever occurs first. [FOLFIRI = Irinotecan, Folinic acid (racemic), Fluorouracil (5-FU)]
  • Cetuximab
FOLFIRIOtherPatients in Arm B will continue therapy with FOLFIRI until PD, unacceptable toxicity, withdrawal of informed consent or death, whatever occurs first.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Histologically confirmed, UICC stage IV adenocarcinoma of the left-sided colon or
                 rectum with metastases (metastatic colorectal cancer), primarily non-resectable,
                 confirmed RAS mutations proven in the primary tumor or metastasis (KRAS ans NRAS exon
                 2, 3, 4)
    
              -  Age ≥ 18 years on day of signing informed consent
    
              -  No previous chemotherapy for metastatic disease
    
              -  Patients suitable for chemotherapy administration
    
              -  ECOG (Eastern Cooperative Oncology Group) status 0-1
    
              -  Consent to liquid biopsy and RAS mutation analysis
    
              -  Estimated life expectancy > 3 months
    
              -  Presence of at least one measurable reference lesion according to the RECIST 1.1
                 criteria (chest CT and abdominal CT 4 weeks or less before enrollment)
    
              -  Adequate bone marrow function defined as: Leukocytes 3.0 x 10 9/L with neutrophils 1.5
                 x 10 9/L, Thrombocytes 100 x 10 9/L, Hemoglobin 9 g/dL
    
              -  Adequate hepatic function defined as: Serum bilirubin 1.5 x ULN (Upper limit of
                 normal), ALAT (Alanine-aminotransferase (= SGPT = serum glutamate pyruvate
                 transaminase) and ASAT (aspartate-aminotransferase (= SGOT = serum glutamate
                 oxalacetate transaminase) 2.5 x ULN (Upper limit of normal) (in the presence of
                 hepatic metastases, ALAT and ASAT 5 x ULN)
    
              -  Adequate renal function: Creatinine clearance ≥ 50 mL/min
    
              -  Adequate cardiac function defined as Normal ECG and echocardiogram with a left
                 ventricular ejection fraction (LVEF) of 55%
    
              -  INR (International normalized ratio) < 1.5 and aPTT (activated Partial thromboplastin
                 time) < 1.5 x ULN (patients without anticoagulation). Therapeutic anticoagulation is
                 allowed if INR and aPTT have remained stable within the therapeutic range for at least
                 2 weeks.
    
              -  Time interval of at least 6 months since last administration of any previous
                 neoadjuvant/adjuvant chemotherapy or radiochemotherapy of the primary tumor in
                 curative treatment intention
    
              -  Any relevant toxicities of prior treatments must have resolved to grade ≤ 1 according
                 to the CTCAE (version 5), except alopecia
    
              -  Women of childbearing potential (WOCBP) should have a negative urine pregnancy test
                 within 72 hours prior to receiving the first dose of study medication.
    
              -  Highly effective contraception for both male and female patients throughout the study
                 and for at least 3 months after last dose of study medication administration if the
                 risk of conception exists. Highly effective contraception has to be in line with the
                 definition of the CTFG (Clinical Trial Facilitation Group) recommendation
    
              -  Signed written informed consent and capacity of understanding the informed consent
    
            Exclusion Criteria:
    
              -  Right sided mCRC
    
              -  Primarily resectable metastases
    
              -  Previous chemotherapy for the colorectal cancer with the exception of adjuvant
                 treatment, completed at least 6 months before entering the study
    
              -  Patients with known brain metastases
    
              -  Symptomatic peritoneal carcinosis
    
              -  Progressive disease before randomization
    
              -  History of acute or subacute intestinal occlusion, inflammatory bowel disease, immune
                 colitis or chronic diarrhea
    
              -  Grade II heart failure (NYHA classification), Myocardial infarction, balloon
                 angioplasty (PTCA) with or without stenting, and cerebral vascular accident/stroke
                 within the past 12 months before enrollment, unstable angina pectoris, serious cardiac
                 arrhythmia according to investigator's judgment requiring medication
    
              -  Active infection with hepatitis B or C
    
              -  Medical or psychological impairments associated with restricted ability to give
                 consent or not allowing conduct of the study
    
              -  Additional cancer; Exceptions include adequately treated basal cell carcinoma of the
                 skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has
                 undergone potentially curative therapy without evidence of recurrence
    
              -  Uncontrolled hypertension
    
              -  Marked proteinuria (nephrotic syndrome)
    
              -  Arterial thromboembolism or severe hemorrhage within 6 months prior to randomization
                 (with the exception of tumor bleeding before tumor resection surgery)
    
              -  Hemorrhagic diathesis or tendency towards thrombosis
    
              -  Participation in a clinical study or experimental drug treatment within 30 days prior
                 to study
    
              -  Known hypersensitivity or allergic reaction to any of the study medications
    
              -  Severe, non-healing wounds, ulcers, bone fractures or an infection requiring systemic
                 therapy
    
              -  Known history of alcohol or drug abuse
    
              -  Known dihydropyrimidine dehydrogenase (DPD) deficiency or glucuronidation deficiency
                 (Gilbert's syndrome) (specific screening not required)
    
              -  Absent or restricted legal capacity
    
              -  For female patients only: Pregnancy (absence to be confirmed by ß-HCG test) or
                 lactating
          
    Maximum Eligible Age:99 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Evaluation of efficacy
    Time Frame:From the start of the first line treatment in the study up to 24 months.
    Safety Issue:
    Description:In terms of progression free survival (PFS)

    Secondary Outcome Measures

    Measure:Overall survival (OS)
    Time Frame:From the start of the first line treatment in the study up to 24 months.
    Safety Issue:
    Description:In experimental and control arms
    Measure:Time to failure of treatment strategy (TFTS)
    Time Frame:From the start of the first line treatment in the study up to 24 months.
    Safety Issue:
    Description:In experimental and control arms
    Measure:PFS (progression free survival) rate
    Time Frame:1 year after the start of the first line treatment.
    Safety Issue:
    Description:In experimental and control arms
    Measure:Depth of response
    Time Frame:From the start of the first line treatment in the study up to 24 months.
    Safety Issue:
    Description:In terms of reduction of tumor mass in experimental and control arms
    Measure:Metastasis resections.
    Time Frame:From the start of the first line treatment in the study up to 24 months.
    Safety Issue:
    Description:In experimental and control arms.
    Measure:Objective response rate (ORR)
    Time Frame:From the start of the first line treatment in the study up to 24 months.
    Safety Issue:
    Description:Defined as patients with partial or complete response (CR or PR) in experimental and control arms
    Measure:Safety profile
    Time Frame:From the start of the first line treatment in the study up to 24 months.
    Safety Issue:
    Description:According to CTCAE (Common Terminology Criteria of Adverse Events), Version 5.0 criteria in experimental and control arms.
    Measure:Identification of driver mutations.
    Time Frame:From the start of the first line treatment in the study up to 24 months.
    Safety Issue:
    Description:In patients with progressive disease (PD) under cetuximab therapy who remain RAS (Rat sarcoma) wild-type in liquid biopsy.
    Measure:Comparison the efficacy in terms of progression free survival (PFS)
    Time Frame:From the start of the first line treatment in the study up to 24 months.
    Safety Issue:
    Description:In patients with conversion to RAS (RAt sarcoma) wild-type in both ddPCR (Droplet Digital PCR) BEAMing with those patients showing conversion to RAS wild-type in ddPCR but not in BEAMing.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:TheraOp

    Trial Keywords

    • Left sided Adenocarcinoma of the Colon
    • RAS mutated

    Last Updated

    September 14, 2020