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

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ClinicalTrials.gov Identifier: NCT03206151
Recruitment Status : Recruiting
First Posted : July 2, 2017
Last Update Posted : October 14, 2020
Sponsor:
Information provided by (Responsible Party):
Taizhou Mabtech Pharmaceutical Co.,Ltd

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: CMAB009 Drug: Irinotecan Drug: Folinic acid Drug: 5-fluorouracil Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 512 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : December 12, 2017
Estimated Primary Completion Date : October 1, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: CMAB009 + FOLFIRI

Drug: 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.

Drug: CMAB009
for injection only
Other Name: Eribitux

Drug: Irinotecan
for injection only
Other Name: Camptosar

Drug: Folinic acid
for injection only
Other Name: leucovorin

Drug: 5-fluorouracil
for injection only
Other Name: Fluoroplex

Active Comparator: FOLFIRI

FOLFIRI 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.

Drug: Irinotecan
for injection only
Other Name: Camptosar

Drug: Folinic acid
for injection only
Other Name: leucovorin

Drug: 5-fluorouracil
for injection only
Other Name: Fluoroplex




Primary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: Baseline up to 24 months ]
    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 :
  1. Best Overall Response Rate(ORR) [ Time Frame: Baseline up to 24 months ]
    Defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as the best overall response based on RECIST1.1

  2. Overall Survival Time (OS) [ Time Frame: Baseline up to 48 months ]
    Defined as the time from randomization to death

  3. Duration of Response [ Time Frame: Baseline up to 24 months ]
    Defined as the time from first assessment of CR or PR to disease progression or death

  4. Number of Subjects with Curative Surgery of Liver Metastases [ Time Frame: Baseline up to 12 months ]
    Defined as the number of subjects who underwent liver metastatic surgery with all lesions been resected completely after start of treatment

  5. Quality of Life Assessment [ Time Frame: Baseline up to 24 months ]
    EORTC-QLQ-C30

  6. Pharmacokinetic Parameters [ Time Frame: Baseline up to 50 days ]
    Area under the curve and the Maximum concentration of CMAB009

  7. Incidence of anti-CMAB009 antibody [ Time Frame: baseline up to 32 weeks ]
    The incidence rate of ADA (anti-CMAB009 antibody)and Nab(neutralizing antibody)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03206151


Contacts
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Contact: Yuankai Shi Professor, Ph.D 13701251865 syuankaipumc@126.com
Contact: Yi Ba Professor, Ph.D 13752157916 dryiba@gmail.com

Locations
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China, Beijing
Cancer hospital Chinese academy of medical sciences Not yet recruiting
Beijing, Beijing, China, 100021
Contact: yuankai shi, doctor    +8613701251865    syuankaipumc@126.com   
China, Tianjin
Tianjing medical university cancer institute and hospital Recruiting
Tianjin, Tianjin, China, 300000
Contact: yi ba, doctor    +8613752157916    yiba999@163.com   
Sponsors and Collaborators
Taizhou Mabtech Pharmaceutical Co.,Ltd
Investigators
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Principal Investigator: Yuankai Shi Professor, Ph.D Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Principal Investigator: Yi Ba Professor, Ph.D Tianjin Medical University Cancer Institute & Hospital
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Responsible Party: Taizhou Mabtech Pharmaceutical Co.,Ltd
ClinicalTrials.gov Identifier: NCT03206151    
Other Study ID Numbers: 009mCRCIIIP
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: October 14, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Leucovorin
Folic Acid
Fluorouracil
Irinotecan
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antidotes
Protective Agents
Vitamin B Complex
Vitamins