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

October 18, 2021 updated by: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Gansu
      • Lanzhou, Gansu, China, 730013
        • Recruiting
        • First Hospital of Lanzhou University
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China, 510655
        • Recruiting
        • Sixth Affiliated Hospital of Sun Yat-sen University
        • Contact:
      • Guangzhou, Guangdong, China, 511316
        • Recruiting
        • Sun Yixian Memorial Hospital,Sun Yat-sen University
        • Contact:
      • Zhanjiang, Guangdong, China, 510180
        • Recruiting
        • Affiliated Hospital of Guangdong Medical University
        • Contact:
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150081
        • Recruiting
        • Cancer Hospital Affiliated to Harbin Medical University
        • Contact:
    • Henan
      • Luoyang, Henan, China, 450062
        • Recruiting
        • The First Affiliated Hospital of Henan University of Scinece and Technology
        • Contact:
    • Hunan
      • Changsha, Hunan, China, 410031
        • Recruiting
        • Hunan Cancer Hospital
        • Contact:
    • Jiangsu
      • Nanjing, Jiangsu, China, 210029
        • Recruiting
        • Jiangsu Province Hospital
        • Contact:
      • Wuxi, Jiangsu, China, 214115
        • Recruiting
        • Affiliated Hospital of Jiangnan University
        • Contact:
      • Yangzhou, Jiangsu, China, 225009
        • Recruiting
        • Subei People's Hospital
        • Contact:
    • Jilin
      • Changchun, Jilin, China, 130021
        • Recruiting
        • Jilin Cancer Hospital
        • Contact:
    • Shandong
      • Jinan, Shandong, China, 250117
        • Recruiting
        • Shandong Cancer Hospital
        • Contact:
    • Shanghai
      • Shanghai, Shanghai, China, 200120
        • Recruiting
        • Shanghai East Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
up to 8-10 months
Overall survival (OS)
Time Frame: up to 20-30 months
Refers to the time between random grouping and death caused by various causes.
up to 20-30 months
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.
up to 30 months
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.
up to 30 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
up to 20-30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 8, 2021

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

June 1, 2024

Study Registration Dates

First Submitted

September 24, 2021

First Submitted That Met QC Criteria

October 4, 2021

First Posted (Actual)

October 5, 2021

Study Record Updates

Last Update Posted (Actual)

October 20, 2021

Last Update Submitted That Met QC Criteria

October 18, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALTN-AK105-II-04

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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