Clinical Trials /

CMAB009 Combined With FOLFIRI First-line Treatment in Patients With RAS/BRAF Wild-type, Metastatic Colorectal Cancer

NCT03206151

Description:

Drugs used against cancer work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as CMAB009, can block tumor growth in different ways. Giving combination chemotherapy together with CMAB009 as first treatment after diagnosis of a metastatic colorectal cancer(first-line treatment)may improve the treatment efficacy. However, it is not yet known whether giving combination chemotherapy together with CMAB009 is more effective than combination chemotherapy alone. This open-label trial investigates the effectiveness of CMAB009 in combination with a standard and effective chemotherapy FOLFIRI(5-Fluorouracil /Folinic acid plus Irinotecan)for RAS/BRAF wild-type, metastatic colorectal cancer in first-line setting, compared to the same chemotherapy alone.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: CMAB009 Combined With FOLFIRI First-line Treatment in Patients With RAS/BRAF Wild-type, Metastatic Colorectal Cancer
  • Official Title: Open, Randomized, Controlled, Multicenter Phase III Study Comparing CMAB009 Plus FOLFIRI Versus FOLFIRI Alone as First-line Treatment for Epidermal Growth Factor Receptor-expressing, RAS/BRAF Wild-type, Metastatic Colorectal Cancer

Clinical Trial IDs

  • ORG STUDY ID: 009mCRCIIIP
  • NCT ID: NCT03206151

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
CMAB009EribituxCMAB009 + FOLFIRI
IrinotecanCamptosarCMAB009 + FOLFIRI
Folinic acidleucovorinCMAB009 + FOLFIRI
5-fluorouracilFluoroplexCMAB009 + FOLFIRI

Purpose

Drugs used against cancer work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as CMAB009, can block tumor growth in different ways. Giving combination chemotherapy together with CMAB009 as first treatment after diagnosis of a metastatic colorectal cancer(first-line treatment)may improve the treatment efficacy. However, it is not yet known whether giving combination chemotherapy together with CMAB009 is more effective than combination chemotherapy alone. This open-label trial investigates the effectiveness of CMAB009 in combination with a standard and effective chemotherapy FOLFIRI5-Fluorouracil /Folinic acid plus Irinotecan)for RAS/BRAF wild-type, metastatic colorectal cancer in first-line setting, compared to the same chemotherapy alone.

Detailed Description

      Patients will be randomly assign in one of the two groups to either receive the combination
      chemotherapy alone or with CMAB009 and will then be treated until progression of the disease
      or unacceptable toxicity occurred. Regular efficacy assessments(every 8 weeks)based on
      imaging will be performed throughout the study together with regular safety assessments.

      After participant discontinuation from the trial, regular updates on further treatments and
      survival status will be requested from the investigator.
    

Trial Arms

NameTypeDescriptionInterventions
CMAB009 + FOLFIRIExperimentalDrug: CMAB009(recombinant chimeric anti-EGFR monoclonal antibody injection), will be administered every 7 days at an initial dose of 400mg/m^2 and 250mg/m^2 for subsequent infusions until progression of disease , withdrawal of consent, or unacceptable toxicity. Drug: Irinotecan bi-weekly irinotecan infusion of 180mg/m^2 on Day 1. Drug: Folinic Acid infusion 400mg/m^2 of folinic acid in on Day 1. Drug: 5-Fluorouracil bolus 5-Fluorouracil bolus of 400mg/m^2 followed by a 46-48 h continuous infusion of 2400mg/m^2. every 2 weeks until progression of disease , withdrawal of consent, or unacceptable toxicity.
  • CMAB009
  • Irinotecan
  • Folinic acid
  • 5-fluorouracil
FOLFIRIActive ComparatorFOLFIRI Drug: Irinotecan bi-weekly irinotecan infusion of 180mg/m^2 on Day 1. Drug: Folinic Acid infusion 400mg/m^2 of folinic acid in on Day 1. Drug: 5-Fluorouracil bolus 5-Fluorouracil bolus of 400mg/m^2 followed by a 46-48 h continuous infusion of 2400mg/m^2. every 2 weeks until progression of disease , withdrawal of consent, or unacceptable toxicity.
  • Irinotecan
  • Folinic acid
  • 5-fluorouracil

Eligibility Criteria

        Inclusion Criteria:

          1. Males or females, Aged ≥18 years and ≤75 years

          2. Diagnosis of histologically confirmed adenocarcinoma of the colon or rectum

          3. First occurrence of metastatic disease(not curatively resected)

          4. RAS/BRAF wild-type status in tumor tissue

          5. At least one measurable lesion by computer tomography(CT) or magnetic resonance
             imaging (MRI)according to RECIST1.1 criteria (not in an irradiated area)

          6. Eastern Cooperative Oncology Group(ECOG)performance status of 0 or 1 at trial entry

          7. Life expectancy of at least 3 months

          8. Medically accepted effective contraception if procreative potential exists(applicable
             for both male and female subjects until at least 90 days after the last dose of trial
             treatment)

          9. Recovery from relevant toxicity due to previous treatment before trial entry

         10. Signed the informed consent form voluntarily

        Exclusion Criteria:

          1. Radiotherapy or surgery(excluding prior diagnostic biopsy)in the 30 days before trial
             treatment

          2. Hepatic, marrow, liver and renal function as follows:

             Marrow: white blood cell count <3.0 × 109/L with neutrophils<1.5 × 109/L, platelet
             count<100×109/L and hemoglobin<90 g/L; Liver function: Total bilirubin >1.5 × upper
             limit of reference range; Aspartate transaminase (AST) and alanine transaminase (ALT)
             > 2.5 × upper limit of reference range , or> 5 × upper reference range in subjects
             with liver metastasis; Renal function: Serum creatinine >1.5 × upper limit of
             reference range, or creatinine clearance<50 mL/min

          3. Previous chemotherapy for CRC adjuvant treatment if terminated <12 months before
             diagnosis of recurrence or metastatic disease

          4. Previous treatment with anti-EGFR monoclonal antibody, epidermal growth factor
             receptor tyrosine kinase inhibitor, or other EGFR targeted inhibitors(such as
             cetuximab, Nimotuzumab, or panitumumab)

          5. Known hypersensitivity or allergic reactions against any of the components of the
             trial treatments

          6. History of organ allograft, autologous stem cell transplantation, or allogeneic stem
             cell transplantation

          7. Other non-permitted concomitant anti-cancer therapies

          8. Known brain metastasis and/or leptomeningeal disease

          9. Previous malignancy other than CRC in the last 5 years except basal cell cancer of the
             skin or preinvasive cancer of the cervix

         10. Participation in another clinical trial within the past 30 days

         11. Concurrent chronic systemic immune therapy or hormone therapy except physiologic
             replacement

         12. Any unstable systemic disease, such as active infection, uncontrolled hypertension,
             unstable angina pectoris, angina in the last 3 months, cardiac failure of New York
             Heart Association classes ≥II, history of myocardial infarction, serious cardiac
             arrhythmias that require drug treatment, liver, kidney or metabolic disease in the
             last 6 months

         13. Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease

         14. severe bone marrow function failure

         15. Any disease, metabolic disorders, or physical/laboratory examination suspected, or
             patients with high risk of complications

         16. Known and declared history of human immunodeficiency virus(HIV)infection

         17. HBV-DNA >1.0 × 103copy

         18. Pregnancy or breastfeeding

         19. Alcohol or drug abuse

         20. Legal incapacity or limited legal capacity
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free Survival (PFS)
Time Frame:Baseline up to 24 months
Safety Issue:
Description:Defined as the duration from randomization until the date of first documented progression or date of death from any cause when death occurred within 90 days of randomization or the last tumor assessment, whichever was later. Progressive disease assessed by RECIST1.1

Secondary Outcome Measures

Measure:Best Overall Response Rate(ORR)
Time Frame:Baseline up to 24 months
Safety Issue:
Description:Defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as the best overall response based on RECIST1.1
Measure:Overall Survival Time (OS)
Time Frame:Baseline up to 48 months
Safety Issue:
Description:Defined as the time from randomization to death
Measure:Duration of Response
Time Frame:Baseline up to 24 months
Safety Issue:
Description:Defined as the time from first assessment of CR or PR to disease progression or death
Measure:Number of Subjects with Curative Surgery of Liver Metastases
Time Frame:Baseline up to 12 months
Safety Issue:
Description:Defined as the number of subjects who underwent liver metastatic surgery with all lesions been resected completely after start of treatment
Measure:Quality of Life Assessment
Time Frame:Baseline up to 24 months
Safety Issue:
Description:EORTC-QLQ-C30
Measure:Pharmacokinetic Parameters
Time Frame:Baseline up to 50 days
Safety Issue:
Description:Area under the curve and the Maximum concentration of CMAB009
Measure:Incidence of anti-CMAB009 antibody
Time Frame:baseline up to 32 weeks
Safety Issue:
Description:The incidence rate of ADA (anti-CMAB009 antibody)and Nab(neutralizing antibody)

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Taizhou Mabtech Pharmaceutical Co.,Ltd

Last Updated

October 9, 2020