A Study of Anlotinib Hydrochloride Capsule Combined With Chemotherapy as First-line Treatment in Subjects With RAS/BRAF Wild Metastatic Colorectal Cancer

A Randomized, Open-label, Parallel Controlled, Multi-center Phase III Study of Anlotinib Hydrochloride Capsule Combined With Chemotherapy as First-line Treatment in Subjects With RAS/BRAF Wild Metastatic Colorectal Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Anlotinib hydrochloride capsule; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 748
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Chizhou, Anhui, China, 247000
      • The People's Hospital of Chizhou
    • Fuzhou, Anhui, China, 350011
      • Fujian Medical University Union Hospital
    • Hefei, Anhui, China, 230001
      • Anhui Provincial Hospital
    • Hefei, Anhui, China, 230031
      • Anhui Cancer Hospital
    • Xuancheng, Anhui, China, 242000
      • Xuancheng People's Hospital
  • Beijing
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing, China, 100029
      • China-Japan Friendship Hospital
    • Beijing, Beijing, China, 100034
      • Peking University Frist Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • The First Affiliated Hospital of Chongqing Medical University
    • Chongqing, Chongqing, China, 408099
      • Fuling Hospital Affiliated to Chongqing University
  • Fujian
    • Fuzhou, Fujian, China, 350011
      • Fujian Cancer Hospital
    • Xiamen, Fujian, China, 361003
      • The First Affiliated Hospital of Xiamen University
  • Gansu
    • Lanzhou, Gansu, China, 730030
      • Lanzhou University Second Hospital
    • Lanzhou, Gansu, China, 730000
      • Gansu Provincial Hospital
    • Lanzhou, Gansu, China, 730000
      • Gansu Provincial Cancer Hospital
    • Lanzhou, Gansu, China, 730030
      • The First Hospital of Lanzhou University
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • The First Affiliated Hospital of Guangzhou Medical University
    • Qingyuan, Guangdong, China, 511518
      • Qingyuan People's Hospital
    • Shantou, Guangdong, China, 515031
      • Cancer Hospital of Shantou University Medical College
    • Zhanjiang, Guangdong, China, 524000
      • Affiliated Hospital of Guangdong Medical University
  • Guangxi
    • Liuzhou, Guangxi, China, 545007
      • Liuzhou Workers' Hospital
  • Guizhou
    • Guiyang, Guizhou, China, 550000
      • The Affiliated Cancer Hospital of Guizhou Medical University
    • Guiyang, Guizhou, China, 550002
      • Guizhou Provincial People's Hospital
  • Hebei
    • Qinhuangdao, Hebei, China, 660000
      • The first hospital of Qinhuangdao
    • Tangshan, Hebei, China, 63001
      • Tangshan people's Hospital
    • Zhangjiakou, Hebei, China, 75000
      • The First affiliated Hospital of Hebei North University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150086
      • The Second Affiliated Hospital of Harbin Medical University
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Affiliated Cancer Hospital
  • Henan
    • Kaifeng, Henan, China, 475000
      • Huaihe Hospital of Henan University
    • Luoyang, Henan, China, 471000
      • The First Affiliated Hospital of Henan University of Science and Technology
    • Nanyang, Henan, China, 473000
      • Nanyang second general hospital
    • Xinyang, Henan, China, 464099
      • Xinyang Central Hospital
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
    • Zhengzhou, Henan, China, 45000
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital Affiliated to Tongji Medical College Hust
    • Xiangyang, Hubei, China, 441021
      • Xiangyang Central Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
  • Inner Mongolia
    • Chifeng, Inner Mongolia, China, 024000
      • Affiliated Hospital of Chifeng University
    • Chifeng, Inner Mongolia, China, 024000
      • Chifeng Municipal Hospital
  • Jiangsu
    • Changzhou, Jiangsu, China, 213000
      • The First Peoples Hospital of Changzhou
    • Nanjing, Jiangsu, China, 210009
      • Jiangsu Cancer Hospital
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital Southeast University
    • Nanjing, Jiangsu, China, 210012
      • Nanjing First Hospital
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province People's Hospital
    • Nanjing, Jiangsu, China, 210022
      • Nanjing Hospital of C.M.
    • Taizhou, Jiangsu, China, 225300
      • Jiangsu Taizhou People's Hospital
    • Taizhou, Jiangsu, China, 225300
      • Taizhou Second People's Hospital
    • Wuxi, Jiangsu, China, 214062
      • Affiliated Hospital of Jiangnan University
    • Yangzhou, Jiangsu, China, 225001
      • Subei People's Hospital of Jiangsu province
  • Jiangxi
    • Nanchang, Jiangxi, China, 330000
      • The Second Affiliated Hospital of Nanchang University
    • Pingxiang, Jiangxi, China, 337055
      • Jiangxi Pingxiang People's Hospital
  • Jilin
    • Changchun, Jilin, China, 130012
      • Jilin Cancer Hospital
    • Changchun, Jilin, China, 130011
      • Jilin Province FAW General Hospital
    • Meihekou, Jilin, China, 135022
      • Meihekou Central Hospital
    • Yanji, Jilin, China, 133099
      • Yanbian University Hospital
  • Liaoning
    • Dalian, Liaoning, China, 116011
      • The First Affiliatde Hospital of DaLin Medical University
    • Jinzhou, Liaoning, China, 121012
      • The First Affiliated Hospital Of Jinzhou Medical University
    • Panjin, Liaoning, China, 124009
      • Genertec Liaoyou Gem Flower Hospital
    • Shenyang, Liaoning, China, 110000
      • Shengjing Hospital of China Medical University
    • Shenyang, Liaoning, China
      • The First Hospital of China Medical University
    • Shenyang, Liaoning, China, 110801
      • Liaoning Cancer Hospital
  • Neimenggu
    • Hohhot, Neimenggu, China, 170000
      • Inner Mongolia Autonomous Region Cancer Hospital
  • Qinghai
    • Xining, Qinghai, China, 810000
      • Qinghai University Affiliated Hospital
  • Shaanxi
    • Hanzhong, Shaanxi, China, 723000
      • Hanzhong Central Hospital
    • Hanzhong, Shaanxi, China, 723000
      • 3201 Hospital
    • Xi'an, Shaanxi, China, 710068
      • Shaanxi Provincial People's Hospital
    • Xi'an, Shaanxi, China, 710061
      • Xi'an International Medical Center Hospital
    • Xi'an, Shaanxi, China, 710068
      • The First Affiliated Hospital of Xi'an Jiaotong University
    • Xi'an, Shaanxi, China, 710068
      • The Second Affiliated Hospital of PLA Air Force Military Medical University
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital Affiliated to Shandong Univercity
    • Jining, Shandong, China, 272001
      • Affiliated hospital of Jining Medical University
    • Liaocheng, Shandong, China, 252000
      • Liaocheng People's Hospital
    • Weifang, Shandong, China, 261041
      • Weifang Hospital of Traditional Chinese Medicine
    • Yantai, Shandong, China, 264000
      • Yantai Yuhuangding Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Shanghai General Hospital
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai, China, 200032
      • Longhua Hospital Shanghai University of Traditional Chinese Medicine
    • Shanghai, Shanghai, China, 200032
      • Shanghai Tenth People's Hospital
    • Shanghai, Shanghai, China, 200080
      • Xinhua Hospital Affiliated To Shanghai Jiaotong University School of Medicine
  • Shanxi
    • Changzhi, Shanxi, China, 46000
      • Changzhi People's Hospital
    • Taiyuan, Shanxi, China, 030000
      • Shanxi Provincial People's Hospital
    • Taiyuan, Shanxi, China, 030000
      • Shanxi Provincial Cancer Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer institute and hospital
    • Tianjin, Tianjin, China, 300450
      • Peking University BinHai Hospital
  • Xinjiang
    • Kashgar, Xinjiang, China, 844000
      • The First People's Hospital of Kashgar
    • Ürümqi, Xinjiang, China, 830000
      • Affiliated Tumor Hospital of Xinjiang Medical University
    • Ürümqi, Xinjiang, China, 830000
      • First Affiliated Hospital of Xinjiang Medical University
  • Yunnan
    • Kunming, Yunnan, China, 650118
      • Yunnan Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310009
      • The Second Affiliated Hospital Zhejiang University School of Medicine
    • Huzhou, Zhejiang, China, 313099
      • Huzhou Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anlotinib + CapeOx; Anlotinib combined with CapeOx(Oxaliplatin+Capecitabine) were used for 4-8 cycles, each cycle is 3 weeks. After 8 cycles, the regimen is changed to Anlotinib combined with Capecitabine.	Drug: Anlotinib hydrochloride capsule; 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)； Drug: Oxaliplatin; Oxaliplatin 130mg/m2, intravenous drip, on Day 1； Drug: Capecitabine; Capecitabine 850mg/m2 administrated orally twice daily from Day 1-14.
Active Comparator: Bevacizumab + CapeOx; Bevacizumab combined with CapeOx(Oxaliplatin+Capecitabine) were used for 4-8 cycles, each cycle is 3 weeks. After 8 cycles, the regimen is changed to Bevacizumab combined with Capecitabine.	Drug: Oxaliplatin; Oxaliplatin 130mg/m2, intravenous drip, on Day 1； Drug: Capecitabine; Capecitabine 850mg/m2 administrated orally twice daily from Day 1-14.; Drug: Bevacizumab; Bevacizumab 7.5mg/kg, intravenous drip, on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) assessed by IRC	PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.	Baseline up to 15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	PFS defined as the time from first dose until the first documented progressive disease (PD) or death from any cause.	Baseline up to 15 months
Overall survival (OS)	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.	Baseline up to 20 months
Objective Response Rate（ORR）	Percentage of subjects achieving complete response (CR) and partial response (PR) .	Baseline up to 15 months
Disease Control Rate (DCR)	Percentage of subjects achieving complete response (CR) and partial response (PR) and stable disease (SD).	Baseline up to 15 months
Duration of Response (DOR)	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.	Baseline up to 15 months

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: April 21, 2021
• First Submitted That Met QC Criteria: April 21, 2021
• First Posted (Actual): April 22, 2021

Study Record Updates

• Last Update Posted (Estimated): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Capecitabine; Oxaliplatin; Bevacizumab
• Other Study ID Numbers: ALTN-Ⅲ-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No