Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Clinical Study to Compare the Efficacy and Safety of AK105 Plus Anlotinib and Capecitabine/Oxaliplatin (CapeOx) , Anlotinib Plus CapeOx, Bevacizumab Plus CapeOx

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05068206
Recruitment Status : Recruiting
First Posted : October 5, 2021
Last Update Posted : October 20, 2021
Sponsor:
Information provided by (Responsible Party):
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Brief Summary:
A clinical study to compare the efficacy and safety of AK105 plus anlotinib and Capecitabine/Oxaliplatin (CapeOx) , anlotinib plus CapeOx, bevacizumab plus CapeOx. A total of 120 cases will be enrolled to the group.

Condition or disease Intervention/treatment Phase
Unresectable Metastatic Colorectal Cancer Drug: AK105 injection Drug: Anlotinib hydrochloride capsule Drug: CapeOX Drug: Bevacizumab Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Open-label Phase II Clinical Study to Evaluate the Efficacy and Safety of AK105 Plus Anlotinib and CapeOx, Anlotinib in Combination With CapeOx Versus Bevacizumab in Combination With CapeOx in the Fisrt-line Treatment of Unresectable Metastatic Colorectal Cancer
Actual Study Start Date : October 8, 2021
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

Arm Intervention/treatment
Experimental: AK105+Anlotinib+CapeOx

Treatment period (6 cycles):

AK105 injection: intravenous drip on Day 1; Anlotinib hydrochloride capsule: oral administration, once daily(QD) ; Oxaliplatin for injection: intravenous infusion on Day 1; Capecitabine tablet:oral administration, twice daily (BID) .

Maintenance period:

AK105 injection: intravenous drip on Day 1; Anlotinib hydrochloride capsule: oral administration, once daily(QD) ; Capecitabine tablet:oral administration, twice daily (BID) . Every 3 weeks is as one cycle.Oxaliplatin is administered for 6 cycles, and AK105 can be administered continuously for 1 year but at most for 2 years. Other cases continue to be administered until the treatment termination event specified in the plan occurs.

Drug: AK105 injection
AK105 is programmed death 1(PD-1) monoclonal antibody

Drug: Anlotinib hydrochloride capsule
Anlotinib is small molecule multi-target tyrosine kinase inhibitor.

Drug: CapeOX
CapeOX is Capecitabine+Oxaliplatin. Capecitabine is a kind of fluorouracil drug, and Oxaliplatin is a kind of platinum anticancer drug.

Experimental: Anlotinib+CapeOx

Treatment period (6 cycles) Anlotinib hydrochloride capsule: QD orally; Oxaliplatin for injection: D1 intravenous infusion on Day 1; Capecitabine tablet: BID oral administration.

Maintenance period:

Anlotinib hydrochloride capsule: QD orally; Capecitabine tablet: BID oral administration. Every 3 weeks is as one cycle, and Oxaliplatin is administered for 6 cycles. Other cases continue to be administered until the treatment termination event specified in the plan occurs.

Drug: Anlotinib hydrochloride capsule
Anlotinib is small molecule multi-target tyrosine kinase inhibitor.

Drug: CapeOX
CapeOX is Capecitabine+Oxaliplatin. Capecitabine is a kind of fluorouracil drug, and Oxaliplatin is a kind of platinum anticancer drug.

Active Comparator: Bevacizumab+CapeOx

Treatment period (6 cycles):

Bevacizumab D1 intravenous infusion; Oxaliplatin D1 intravenous infusion; Capecitabine BID oral administration.

Maintenance period:

Bevacizumab D1 intravenous infusion; Capecitabine BID oral administration. Every 3 weeks is as one cycle, and Oxaliplatin is administered for 6 cycles. Other cases continue to be administered until the treatment termination event specified in the plan occurs.

Drug: CapeOX
CapeOX is Capecitabine+Oxaliplatin. Capecitabine is a kind of fluorouracil drug, and Oxaliplatin is a kind of platinum anticancer drug.

Drug: Bevacizumab
Bevacizumab is a recombinant human monoclonal antibody.




Primary Outcome Measures :
  1. Disease progression-free survival(PFS) [ Time Frame: up to 8-10 months ]
    According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the time between the beginning of randomization and the first occurrence of objective disease progression or recurrence or death from various causes (whichever occurs first).

  2. Overall survival (OS) [ Time Frame: up to 20-30 months ]
    Refers to the time between random grouping and death caused by various causes.

  3. Objective remission rates(ORR) [ Time Frame: up to 30 months ]
    Percentage of subjects with complete remission (CR) or partial remission (PR) as determined by RECIST 1.1.

  4. Disease Control Rate (DCR) [ Time Frame: up to 30 months ]
    Percentage of subjects with CR, PR, or disease stabilization (SD) at 6 weeks or more as determined by RECIST 1.1.


Secondary Outcome Measures :
  1. Duration of disease remission (DOR) [ Time Frame: up to 20-30 months ]
    For subjects whose best remission is CR or PR, it is defined as from the date when tumor remission is first recorded to the date when disease progression is first recorded or the date of death from any cause (whichever occurs first).



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.


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

Inclusion Criteria:

  • The subjects shall volunteer to join in the research and sign the informed consent under the good compliance.
  • Aged: 18-75 (calculated on the date of signing informed consent); the physical status of Eastern cooperative oncology group 0~1; expected lifetime≥3 months.
  • Unresectable and untreated metastatic colorectal adenocarcinoma patients diagnosed by histopathology Union for International Cancer Control (UICC) ,American Joint Committee on Cance( AJCC) tumor node metastasis staging system for colorectal cancer (8th edition in 2017) is clearly IV stage.
  • Subjects who have not received systematic treatment for colorectal cancer before, including chemotherapy, targeted therapy and immunotherapy; Subjects with tumor recurrence or metastasis at least 6 months after the end of previous adjuvant or neoadjuvant chemotherapy.
  • It can provide previously stored tumor tissue specimens or biopsy to collect tumor focus tissues for detecting programmed death 1 expression and kirsten rat sarcoma viral oncogene/neuroblastoma rat sarcoma viral oncogene mutation.
  • According to RECIST 1.1 criterion, there is at least one measurable lesion. It is required that the selected target lesion has not received local treatment before, or the selected target lesion is located in the previous local treatment area, but it is determined as progressive disease by imaging examination.
  • Good organ function (no blood transfusion, no hematopoietic stimulating factor, no infusion of albumin or blood products within 14 days before randomization).
  • Female subjects of childbearing age should agree that contraceptive measures (such as abstinence, intrauterine device, contraceptive pills or condoms) must be used during the study and within 6 months after the end of the study; Serum pregnancy test was negative within 7 days before the study was enrolled, and it must be a non-lactating subject; Male subjects should agree that contraception must be used during the study period and within 6 months after the end of the study period.

Exclusion Criteria:

  • 1) Combined diseases and medical history:

    1. Other malignant tumors have occurred or are currently suffering at the same time within 3 years. The following conditions can be included: cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumor [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invasive basement membrane)];
    2. Factors which affecting oral administration of drugs (such as inability to swallow, chronic diarrhoea and ileus, etc.);
    3. There is or tends to be gastrointestinal bleeding or perforation within 4 weeks before inclusion;
    4. Subjects with ulcerative colitis and Crohn's disease; Subjects with active inflammatory bowel disease within 4 weeks before inclusion;
    5. Uncontrollable pleural effusion and ascites requiring repeated drainage, and moderate and above hydropertcardium;
    6. Unmitigated toxic reactions above Common Terminology Criteria for Adverse Events S1 due to any previous treatment, excluding alopecia;
    7. Major surgical treatment, open biopsy or obvious traumatic injury were received within 28 days before inclusion (except tissue biopsy under gastrointestinal endoscope);
    8. Imaging(CT or MRI) showed that the tumor invaded large blood vessels or had unclear boundary with blood vessels;
    9. Subjects with hematemesis and hematochezia symptoms within 3 months before screening, and the daily bleeding volume is ≥ 2. 5 ml, or any bleeding event ≥ Common Terminology Criteria for Adverse Events S3, or subjects with any bleeding signs or medical history judged by researchers to be unsuitable for inclusion regardless of severity;
    10. There are unhealed wounds, ulcers or fractures;
    11. Arteriovenous thrombosis occurred within 6 months, such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc;
    12. Subjects who have a history of psychotropic drug abuse and can't quit;
    13. Subjects with any severe and/or uncontrolled diseases, including:

Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after standard antihypertensive treatment); Suffering from unstable angina pectoris/ S2 or over cardiogenic chest pain; Myocardial infarction occurred within 12 months before randomization; S1or over heart failure (New York Heart Association (NYHA) grade); Restrictive cardiomyopathy; S2 or over atrioventricular block, arrhythmia that cannot be stably controlled by drugs [including QTc ≥ 450 ms (male) and QTc ≥ 470 ms (female)], and arrhythmia that may have potential influence on experimental treatment; Active infection (≥ Common Terminology Criteria for Adverse Events S2 infection); Decompensated cirrhosis, active hepatitis *; (* Active hepatitis (hepatitis B reference: HBsAg positive, and HBV DNA positive (> 2500 copies/ml or > 500IU/ml); Hepatitis C reference: HCV antibody positive, and HCV virus titer detection value exceeds the upper limit of normal value); Note: Subjects with positive hepatitis B surface antigen or core antibody and hepatitis C patients who meet the entry conditions need continuous antiviral treatment to prevent virus activation. ) Subjects with renal failure requiring hemodialysis or peritoneal dialysis; Have a history of immunodeficiency, including HIV positive or suffering from other acquired and congenital immunodeficiency diseases, or have a history of organ transplantation; Diabetes mellitus is poorly controlled (fasting blood glucose (FBG) > 10mmol/L) Urine routine indicates that urine protein is ≥ + +, and it is confirmed that 24-hour urine protein quantity is > 1.0 g; Subjects who have a definite history of neurological or mental disorders, including epilepsy or dementia, and need treatment.

  • 2) Tumor-related symptoms and treatment:

    1. Have received surgery (except previous diagnostic biopsy), radiotherapy, chemotherapy or other anti-cancer therapy within 4 weeks before inclusion (wahsout period is calculated from the end of the last treatment); Note: Those who have received local radiotherapy in the past can be enrolled if the following conditions are met: the end of radiotherapy is more than 4 weeks from the start of study treatment (brain radiotherapy is more than 2 weeks), and the target lesions selected in this study are not in the radiotherapy area; Or the target lesion is located in the radiotherapy area, but the progress has been confirmed;
    2. Within 2 weeks before joining the group, subjects who received ready-for-use traditional Chinese medicine (including Compound Mylabris Capsule, Kang'ai Injection, Kanglaite Capsule/Injection, Aidi Injection, Brucea javanica Oil Injection/Capsule, Xiaoaiping Tablet/Injection, Cinobufagin Capsule, etc.) with anti-tumor indications specified in National Medical Products Administration approved drug instructions;
    3. Subjects who have previously received anti-PD-1 or anti-PD-L1/PD-L2 preparations or other treatments acting on T cell co-stimulation targets or checkpoints;
    4. Previous postoperative adjuvant therapy containing anti-vascular or anti-epidermal growth factor receptor targeted drugs (including but not limited to bevacizumab, cetuximab, panitumumab, aflibercept, regorafenib, etc.)
    5. Central nervous system metastasis with symptoms or symptoms control time less than 2 months;
  • 3) Research therapy related:

    1. Vaccination history of live attenuated vaccine within 28 days before enrollment or plan to vaccinate live attenuated vaccine during the study period;
    2. Subjects who are known to be allergic to research drugs or excipients, or allergic to similar drugs;
    3. Active autoimmune diseases requiring systemic treatment (such as the use of disease-relieving drugs, corticosteroids or immunosuppressants) occurred within 2 years before enrollment. Alternative therapies (such as thyroxine, insulin or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic treatment;
    4. Diagnosed as immunodeficiency or receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy (dose > 10mg/day prednisone or other equivalent hormone), and continuing to be used within 2 weeks after the first administration;
  • Participated in clinical trials of other anti-tumor drugs within 4 weeks before joining the group (washout period was calculated from the end of the last treatment);
  • According to the researcher's judgment, there are accompanying diseases that seriously endanger the safety of the subjects or affect the completion of the study, or there are other reasons why the subjects are not suitable for enrollment.

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): NCT05068206


Contacts
Layout table for location contacts
Contact: Jin Li, Doctor 13761222111 lijin@csco.org.cn

Locations
Layout table for location information
China, Gansu
First Hospital of Lanzhou University Recruiting
Lanzhou, Gansu, China, 730013
Contact: Xiaoming Hou, Doctor    13609366286    1795950416@qq.com   
China, Guangdong
Sixth Affiliated Hospital of Sun Yat-sen University Recruiting
Guangzhou, Guangdong, China, 510655
Contact: Yanhong Deng, Doctor    13925106525    13925106525@163.com   
Sun Yixian Memorial Hospital,Sun Yat-sen University Recruiting
Guangzhou, Guangdong, China, 511316
Contact: Zhonghua Chu, Doctor    13501502570    Chu9009@163.com   
Affiliated Hospital of Guangdong Medical University Recruiting
Zhanjiang, Guangdong, China, 510180
Contact: Zhong Xie, Doctor    13828234566    xiexieg@126.com   
China, Heilongjiang
Cancer Hospital Affiliated to Harbin Medical University Recruiting
Harbin, Heilongjiang, China, 150081
Contact: Yuxian Bai, Doctor    13945095085    15553115688@163.com   
China, Henan
The First Affiliated Hospital of Henan University of Scinece and Technology Recruiting
Luoyang, Henan, China, 450062
Contact: Jun Yao, Doctor    13663790098    yaojun74@163.com   
China, Hunan
Hunan Cancer Hospital Recruiting
Changsha, Hunan, China, 410031
Contact: Zhenyang Liu, Doctor    18673181133    1323081926@qq.com   
China, Jiangsu
Jiangsu Province Hospital Recruiting
Nanjing, Jiangsu, China, 210029
Contact: Lingjun Zhu, Doctor    13951807457    13951807457@139.com   
Affiliated Hospital of Jiangnan University Recruiting
Wuxi, Jiangsu, China, 214115
Contact: Yong Mao, Doctor    18651861690    mydoctorwx@aliyun.com   
Subei People's Hospital Recruiting
Yangzhou, Jiangsu, China, 225009
Contact: Xizhi Zhang, Doctor    18051060361    18051060361@163.com   
China, Jilin
Jilin Cancer Hospital Recruiting
Changchun, Jilin, China, 130021
Contact: Ying Cheng, Doctor    0431-80596065    jl.cheng@163.com   
China, Shandong
Shandong Cancer Hospital Recruiting
Jinan, Shandong, China, 250117
Contact: Bo Liu, Doctor    15553115688    15553115688@163.com   
China, Shanghai
Shanghai East Hospital Recruiting
Shanghai, Shanghai, China, 200120
Contact: Jin Li, Doctor    13761222111    lijin@csco.org.cn   
Sponsors and Collaborators
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Layout table for additonal information
Responsible Party: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
ClinicalTrials.gov Identifier: NCT05068206    
Other Study ID Numbers: ALTN-AK105-II-04
First Posted: October 5, 2021    Key Record Dates
Last Update Posted: October 20, 2021
Last Verified: October 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors