Clinical Trials /

Study of Abituzumab in Combination With Cetuximab and FOLFIRI in Patients With Metastatic Colorectal Cancer.

NCT03688230

Description:

The purpose of this study is to evaluate the safety and efficacy of the experimental drug abituzumab (EMD525797) in combination with cetuximab and FOLFIRI in RAS wild-type, left-sided, metastatic colorectal cancer patients with high ανβ6 integrin expression.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Abituzumab in Combination With Cetuximab and FOLFIRI in Patients With Metastatic Colorectal Cancer.
  • Official Title: AMELION: A Randomized, Double Blinded, Phase 2, Efficacy and Safety Study of Abituzumab (EMD 525797) in Combination With Cetuximab and FOLFIRI Versus Placebo in Combination With Cetuximab and FOLFIRI in First-line RAS Wild-type, Left-sided, Metastatic Colorectal Cancer Patients With High ανβ6 Integrin Expression.

Clinical Trial IDs

  • ORG STUDY ID: AP218797
  • SECONDARY ID: 2018-003439-31
  • SECONDARY ID: AIO-KRK-0318/ass
  • NCT ID: NCT03688230

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
abituzumabEMD525797Abituzumab + Cetuximab + FOLFIRI

Purpose

The purpose of this study is to evaluate the safety and efficacy of the experimental drug abituzumab (EMD525797) in combination with cetuximab and FOLFIRI in RAS wild-type, left-sided, metastatic colorectal cancer patients with high ανβ6 integrin expression.

Trial Arms

NameTypeDescriptionInterventions
Abituzumab + Cetuximab + FOLFIRIExperimentalCetuximab: 400 mg/m2 over 120 min followed by 250 mg/m2 weekly 60 min or 500 mg/m2 every two weeks, initially 120 min followed by 60 to 90 min (60 min [± 5 min] after completion of the cetuximab infusion) Abituzumab 1000 mg: every 2 weeks for 60 min (60 min [± 5 min] after completion of the abituzumab infusion) FOLFIRI: every 2 weeks Irinotecan 180 mg/m² IV, 30 - 90 min day 1 Folinic acid (racemic) 400 mg/m² IV, 120 min day 1 5-FU 400 mg/m² bolus day 1 5-FU 2400 mg/m² IV over a period of 46 h day 1-2
  • abituzumab
Placebo + Cetuximab + FOLFIRIPlacebo ComparatorCetuximab: 400 mg/m2 over 120 min followed by 250 mg/m2 weekly 60 min or 500 mg/m2 every two weeks, initially 120 min followed by 60 to 90 min (60 min [± 5 min] after completion of the cetuximab infusion) Placebo: every 2 weeks for 60 min (60 min [± 5 min] after completion of the placebo infusion) FOLFIRI: every 2 weeks Irinotecan 180 mg/m² IV, 30 - 90 min day 1 Folinic acid (racemic) 400 mg/m² IV, 120 min day 1 5-FU 400 mg/m² bolus day 1 5-FU 2400 mg/m² IV over a period of 46 h day 1-2

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Signed and dated written informed consent prior to any study specific procedure;
    
              2. Age: ≥18 years;
    
              3. Evidence of newly diagnosed stage IV metastatic colorectal cancer. Primary tumor
                 location on the left side of the Colon (including left splenic flexure) or rectum;
    
              4. Demonstrated wild-type RAS mutation status in the tumor (primary tumor or metastasis)
                 by local assessment;
    
              5. Tumor tissue specimen shows high ανβ6 integrin expression, as determined by central
                 laboratory assessment;
    
              6. Tumor tissue specimen (formalin-fixed, paraffin-embedded block) preferably from
                 primary resection and/or if available from a surgical sample from metastatic site must
                 be available for central laboratory based ανβ6 integrin expression analysis. (No Fine
                 Needle Aspiration [FNA] will be accepted);
    
              7. At least 1 radiographically documented measurable lesion in a previously
                 non-irradiated area according to RECIST (Version 1.1), i.e., this lesion must be
                 adequately measurable in at least 1 dimension (longest diameter to be recorded) as ≥2
                 cm by conventional techniques or ≥1 cm by spiral CT scan;
    
              8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1;
    
              9. Females of childbearing potential must have a negative pregnancy test at screening and
                 be willing to have additional pregnancy tests during the study;
    
            Exclusion Criteria:
    
              1. Demonstrated any RAS or BRAF mutation;
    
              2. Prior anti-EGFR or other targeted therapy;
    
              3. Prior chemotherapy of the colorectal cancer, except for (neo) adjuvant therapy
                 completed at least 6 months before randomization;
    
              4. Radiotherapy (localized radiotherapy for pain relief is allowed to non-target
                 lesions);
    
              5. Investigational drug treatment for the treatment of malignancies in the past;
    
              6. Concurrent participation in another interventional clinical study;
    
              7. Pregnancy (exclusion confirmed with beta-hCG test) or lactation;
    
              8. Any history or evidence of brain metastases or leptomeningeal metastases;
    
              9. History of secondary malignancy within the past 5 years, except for basal cell
                 carcinoma or carcinoma in situ of the cervix uteri, if treated with curative intent;
    
             10. Concomitant chronic systemic immune or hormone therapy not indicated in this study
                 protocol (except for physiologic replacement; steroids up to 10 mg per day of
                 prednisone equivalent or topical and inhaled steroids are allowed);
    
             11. Clinically relevant coronary artery disease (New York Heart Association [NYHA]
                 functional angina classification III/IV), congestive heart failure (NYHA III/IV), or
                 clinically relevant cardiomyopathy;
    
             12. Uncontrolled hypertension defined as systolic blood pressure >160 mmHg and/or
                 diastolic blood pressure >100 mmHg under resting conditions;
    
             13. History of myocardial infarction in the last 12 months, or a high risk of uncontrolled
                 arrhythmia, coagulation disorder associated with bleeding or recurrent thrombotic
                 events, with the exception of arterial fibrillation treated with anti-coagulants;
    
             14. Recent peptic ulcer disease (endoscopically proven) within 6 months of randomization,
                 chronic inflammatory bowel disease, or acute/chronic ileus;
    
             15. Active infection (requiring IV antibiotics and/or antiviral therapy), including active
                 tuberculosis, active or chronic Hepatitis B or C, or ongoing HIV infection, AIDS;
    
             16. Presence of any contra-indications or known hypersensitivity to treatment with
                 abituzumab, cetuximab, and FOLFIRI, or to any of the excipients of these drugs;
    
             17. Concomitant treatment with prohibited medications;
    
             18. Medical or psychological conditions that would not permit the patient to complete the
                 study.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Progression Free Survival (PFS)
    Time Frame:16 months
    Safety Issue:
    Description:Progression free survival per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as determined by investigator.

    Secondary Outcome Measures

    Measure:Overall Survival (OS)
    Time Frame:68 months
    Safety Issue:
    Description:The overall survival is defined as the time from randomization to death from any cause.
    Measure:Objective Response Rate (ORR)
    Time Frame:16 months
    Safety Issue:
    Description:ORR will be estimated as the proportion of responders in each treatment arm, defined as a patient whose best overall response is PR or better during the treatment period according to RECIST 1.1.
    Measure:Depth of Response (DPR)
    Time Frame:16 months
    Safety Issue:
    Description:Depth of response will be estimated as the maximum percent tumor shrinkage during treatment.
    Measure:Early Tumor Shrinkage (ETS)
    Time Frame:68 months
    Safety Issue:
    Description:ETS will be estimated as the proportion of patients achieving a ≥20 % decrease from baseline in the sum of longest tumor diameters.
    Measure:Secondary Resection Rate With a Potentially Curative Intent
    Time Frame:16 months
    Safety Issue:
    Description:Patients for whom the resectability of metastases becomes evident during the study therapy should undergo a surgical resection of the metastases.
    Measure:Number of participants with treatment-related adverse events summarized by CTCAE severity grade (v5.0).
    Time Frame:68 months
    Safety Issue:
    Description:Adverse events will be summarized by body system, preferred term, severity, and relationship to treatment

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:SFJ Pharmaceuticals X, LTD.

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