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

NCT05068206 | Unknown Phase 2

• 1 other identifier: ALTN-AK105-II-04
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 13

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.

Conditions

Unresectable Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (4)

• Disease progression-free survival(PFS)

  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)

  Refers to the time between random grouping and death caused by various causes.

  up to 20-30 months

• Objective remission rates(ORR)

  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)

  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 Outcomes (1)

• Duration of disease remission (DOR)

  up to 20-30 months

Study Arms (3)

AK105+Anlotinib+CapeOx

EXPERIMENTAL

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; Drug: Anlotinib hydrochloride capsule; Drug: CapeOX

Anlotinib+CapeOx

EXPERIMENTAL

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; Drug: CapeOX

Bevacizumab+CapeOx

ACTIVE COMPARATOR

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; Drug: Bevacizumab

Interventions

AK105 injection DRUG

AK105 is programmed death 1（PD-1） monoclonal antibody

AK105+Anlotinib+CapeOx

Anlotinib hydrochloride capsule DRUG

Anlotinib is small molecule multi-target tyrosine kinase inhibitor.

AK105+Anlotinib+CapeOx; Anlotinib+CapeOx

CapeOX DRUG

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

AK105+Anlotinib+CapeOx; Anlotinib+CapeOx; Bevacizumab+CapeOx

Bevacizumab DRUG

Bevacizumab is a recombinant human monoclonal antibody.

Bevacizumab+CapeOx

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \) Combined diseases and medical history:
• 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 \[Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invasive basement membrane)\];
• Factors which affecting oral administration of drugs (such as inability to swallow, chronic diarrhoea and ileus, etc.);
• Uncontrollable pleural effusion and ascites requiring repeated drainage, and moderate and above hydropertcardium;
• Unmitigated toxic reactions above Common Terminology Criteria for Adverse Events S1 due to any previous treatment, excluding alopecia;
• Imaging(CT or MRI) showed that the tumor invaded large blood vessels or had unclear boundary with blood vessels;
• There are unhealed wounds, ulcers or fractures;
• 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;
• Subjects who have a history of psychotropic drug abuse and can't quit;
• 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.
• \) Tumor-related symptoms and treatment:
• 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;
• 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;
• 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.)

Sponsors & Collaborators

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

Study Sites (13)

First Hospital of Lanzhou University

Lanzhou, Gansu, 730013, China

RECRUITING

Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

RECRUITING

Sun Yixian Memorial Hospital,Sun Yat-sen University

Guangzhou, Guangdong, 511316, China

RECRUITING

Affiliated Hospital of Guangdong Medical University

Zhanjiang, Guangdong, 510180, China

RECRUITING

Cancer Hospital Affiliated to Harbin Medical University

Harbin, Heilongjiang, 150081, China

RECRUITING

The First Affiliated Hospital of Henan University of Scinece and Technology

Luoyang, Henan, 450062, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410031, China

RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

RECRUITING

Affiliated Hospital of Jiangnan University

Wuxi, Jiangsu, 214115, China

RECRUITING

Subei People's Hospital

Yangzhou, Jiangsu, 225009, China

RECRUITING

Jilin Cancer Hospital

Changchun, Jilin, 130021, China

RECRUITING

Shandong Cancer Hospital

Jinan, Shandong, 250117, China

RECRUITING

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200120, China

RECRUITING

MeSH Terms

Interventions

Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Jin Li, Doctor

CONTACT

13761222111; lijin@csco.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2021
• First Posted: October 5, 2021
• Study Start: October 8, 2021
• Primary Completion: December 1, 2023
• Study Completion: June 1, 2024
• Last Updated: October 20, 2021

Record last verified: 2021-10

Locations

CN (13)