Clinical trial NCT03206151: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Taizhou Mabtech Pharmaceutical Co.,Ltd
Sponsor class: INDUSTRY
First posted: 2017-07-02
Enrollment: 520
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Tumor assessments are conducted every 8 weeks after randomization until the end of the study, an average of 1 year.
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Tumor assessments are conducted every 8 weeks after randomization until the end of the study, an average of 1 year.
measure: Overall Survival（OS）
timeFrame: From randomization until the end of the study, an average of 1 year.
measure: Disease Control Rate (DCR)
timeFrame: Tumor assessments are conducted every 8 weeks after randomization until the end of the study, an average of 1 year.
measure: Time to Response (TTR)
timeFrame: Tumor assessments are conducted every 8 weeks after randomization until the end of the study, an average of 1 year.
measure: Quality of Life Assessment Indicators
timeFrame: Assessments are conducted at baseline and subsequent visits every 8 weeks until withdrawal from the study and entry into the follow-up period.
measure: Resection Rate of Hepatic Metastasis
timeFrame: From randomization to the end of study
measure: Safety Endpoint
timeFrame: From enrollment to the end of study
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer hospital Chinese academy of medical sciences
state: Beijing
city: Tianjin
country: China
facility: Tianjing medical university cancer institute and hospital
state: Tianjin
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Yuankai Shi Professor, Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin Medical University Cancer Institute and Hospital
name: Yi Ba Professor, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: