Metastatic Colorectal Cancer
Conditions
Brief summary
This is an open label, randomized, phase Ⅲ study to treat subjects with RAS/BRAF wild-type, unresectable metastatic colorectal cancer. The patients will be randomized into two arms consist of Anlotinib (3 weeks/cycle) + CapeOx and Bevacizumab (3 week/cycle) + CapeOx at a ratio of 1:1. This study is conducted to assess the efficacy and safety of Anlotinib and Chemotherapy as first-line treatment in subjects with RAS/BRAF wild-type Metastatic Colorectal Cancer.
Interventions
Anlotinib hydrochloride capsule 12mg given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)；
DRUGBevacizumab
Bevacizumab 7.5mg/kg, intravenous drip, on Day 1
DRUGOxaliplatin
Oxaliplatin 130mg/m2, intravenous drip, on Day 1；
DRUGCapecitabine
Capecitabine 850mg/m2 administrated orally twice daily from Day 1-14.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Understood and Signed an informed consent form. 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1；Life expectancy≥ 3 months. 3\. Histologically or cytologically confirmed unresectable metastatic colorectal cancer. 4\. Has RAS/BRAF wild-type. 5. Has at least one measurable lesion. 6. Adequate organ function. 7.Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study (such as intrauterine devices , contraceptives or condoms) ; No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the randomization.
Exclusion criteria
* 1.Has dMMR/MSI-H. 2. Combined with the following diseases or medical history: 1. Previous or co-existing malignancies within 3 years except for cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors； 2. Has many factors that affect the oral administration of drugs； 3. Has Gastrointestinal bleeding or perforation within 4 weeks before the first dose； 4. Has active inflammatory bowel disease within 4 weeks before the first dose； 5. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage； 6. Patients whose adverse events (except hair loss) caused by previous treatment did not recover to ≤CTCAE 1 degree； 7. Has received major surgical procedure、biopsy or obvious traumatic injury within 28 days before the first dose； 8. Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary of blood vessels is unclear； 9. Has any bleeding event or the level of bleeding events ≥ CTCAE 3； 10. Has unhealed wounds, ulcerative or fractures； 11. Has arterial or venous thromboembolic events occurred within 6 months, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism； 12. Has a history of psychotropic substance abuse and are unable to quit ； 13. Has any severe and / or uncontrolled disease； 3.Tumor related symptoms and treatment <!-- --> 1. Has received chemotherapy, surgery, radiotherapy, and other anti-cancer therapy within 4 weeks before the first dose. 2. Has received anti-tumor Chinese patent medicine which were approved by NMPA Within 2 weeks before the first dose. 3. Previous adjuvant therapy containing anti-vascular or anti-EGFR targeted drugs. 4. Has received systematic treatment for advanced colorectal cancer. 5. Has symptomatic brain metastases or control of symptoms \< 2 month. 4.Has participated in other anticancer drug clinical trials within 4 weeks. 5.According to the judgement of the researchers, there are other factors that may lead to the termination of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) assessed by IRC | Baseline up to 15 months | PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | Baseline up to 15 months | PFS defined as the time from first dose until the first documented progressive disease (PD) or death from any cause. |
| Overall survival (OS) | Baseline up to 20 months | OS defined as the time from the first dose to death from any cause. Survival time was censored at the date of last contact for patients who were still alive or lost to follow-up. |
| Objective Response Rate（ORR） | Baseline up to 15 months | Percentage of subjects achieving complete response (CR) and partial response (PR) . |
| Disease Control Rate (DCR) | Baseline up to 15 months | Percentage of subjects achieving complete response (CR) and partial response (PR) and stable disease (SD). |
| Duration of Response (DOR) | Baseline up to 15 months | DOR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurred first. |
Countries
China
Outcome results
None listed