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
Overview
- Phase
- Phase 2
- Intervention
- AK105 injection
- Conditions
- Unresectable Metastatic Colorectal Cancer
- Sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Enrollment
- 120
- Locations
- 13
- Primary Endpoint
- Objective remission rates(ORR)
- Last Updated
- 4 years ago
Overview
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.
Investigators
Eligibility 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
- •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.);
- •There is or tends to be gastrointestinal bleeding or perforation within 4 weeks before inclusion;
- •Subjects with ulcerative colitis and Crohn's disease; Subjects with active inflammatory bowel disease within 4 weeks before inclusion;
- •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;
- •Major surgical treatment, open biopsy or obvious traumatic injury were received within 28 days before inclusion (except tissue biopsy under gastrointestinal endoscope);
- •Imaging(CT or MRI) showed that the tumor invaded large blood vessels or had unclear boundary with blood vessels;
- •Subjects with hematemesis and hematochezia symptoms within 3 months before screening, and the daily bleeding volume is ≥
Arms & Interventions
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.
Intervention: AK105 injection
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.
Intervention: Anlotinib hydrochloride capsule
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.
Intervention: CapeOX
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.
Intervention: Anlotinib hydrochloride capsule
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.
Intervention: CapeOX
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.
Intervention: CapeOX
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.
Intervention: Bevacizumab
Outcomes
Primary Outcomes
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.
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.
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).
Overall survival (OS)
Time Frame: up to 20-30 months
Refers to the time between random grouping and death caused by various causes.
Secondary Outcomes
- Duration of disease remission (DOR)(up to 20-30 months)