A Phase II/III, Double-blind, Randomized, Multi-center Study of HR070803 in Combination With Oxaliplatin, 5-fluorouracil, Calcium Folinate and Bevacizumab Versus FOLFOX in Combination With Bevacizumab for First-line Treatment of Advanced Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 669
- 试验地点
- 1
- 主要终点
- Adverse Events (AE) According to NCI-CTCAE v5.0（Phase II）
研究概览
简要总结
This is a double-blind, randomized, multi-center, II/III study in at least 606 patients with advanced colorectal cancer. The study is being conducted to evaluate the safety of HR070803 combined with oxaliplatin, 5-FU/LV and bevacizumab in phase II and to evaluate the efficacy of HR070803 in combination with oxaliplatin, 5-FU/LV, and bevacizumab versus HR070803 simulator in combination with FOLFOX and bevacizumab for first-line treatment of patients with unresectable metastatic colorectal cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female who is 18-75 years of age;
- •Histologically-confirmed metastatic and unresectable (Stage IV as defined by American Joint Committee on Cancer [AJCC eighth edition]) colorectal adenocarcinoma
- •No previous systemic antitumor therapy (including but not limited to systemic chemotherapy, molecularly targeted therapy, immunotherapy, biotherapy, and other investigational therapeutic agents) for colorectal cancer (patients with confirmed relapse ≥6 months after the last administration of neoadjuvant or adjuvant therapy can be enrolled);
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 ;
- •Life expectancy of ≥ 6 months;
- •Vital organ functions meet the criteria.
排除标准
- •With confirmed MMR deficient (dMMR) or microsatellite instability high (MSI-H).
- •With central nervous system metastases.
- •Previous oxaliplatin-containing chemotherapy within 12 months prior to enrolment.
- •Previous treatment with irinotecan, immune checkpoint inhibitor, anti-epidermal growth factor receptor or any anti-angiogenic drug.
- •Patients with large amount of pleural effusion, ascites or pericardial effusion that could not reach a stable state within 2 weeks prior to enrolment.
- •Severe gastrointestinal dysfunction (inflammation or diarrhea > grade 1).
- •With diagnosed interstitial lung disease.
- •Severe cardiovascular and cerebrovascular diseases.
- •Peripheral neuropathy > grade
- •Intestinal obstruction within the 6 months prior to enrolment.
- •Gastrointestinal perforation, gastrointestinal fistula, intraperitoneal abscess, and non-gastrointestinal fistula (e.g. tracheoesophageal fistula) within 6 months prior to enrolment.
- •Patients with CTCAE≥ grade 3 gastrointestinal bleeding within 6 months prior to enrolment, or any grade gastrointestinal bleeding within 1 month prior to enrolment.
- •Patients with CTCAE≥ grade 3 extra-gastrointestinal bleeding within 6 months prior to enrolment, or CTCAE≥ grade 2 extra-gastrointestinal bleeding within 3 months prior to enrolment.
- •Uncontrolled hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg under regular antihypertensive therapy), and a history of hypertensive crisis or hypertensive encephalopathy.
- •History of hypersensitivity or contraindications to any of irinotecan liposomes/simulator, irinotecan, other liposomal products, 5-FU, calcium folinate, oxaliplatin, bevacizumab.
研究组 & 干预措施
HR070803
HR070803 plus oxaliplatin, 5-FU/LV, bevacizumab
干预措施: HR070803 plus oxaliplatin, 5-FU/LV, bevacizumab (Drug)
HR070803 simulator
HR070803 simulator plus oxaliplatin, 5-FU/LV, bevacizumab
干预措施: HR070803 simulator plus oxaliplatin, 5-FU/LV, bevacizumab (Drug)
结局指标
主要结局
Adverse Events (AE) According to NCI-CTCAE v5.0（Phase II）
时间窗: From Baseline to primary completion date, about 48 months
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant after signing the informed consent form and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that is temporally associated with the use of study treatment, is also an AE.
Serious Adverse Events (SAE)（Phase II）
时间窗: From Baseline to primary completion date, about 48 months
An SAE is defined as any of the following adverse events in a participant or clinical investigation participant after signing the informed consent form and which does not necessarily have to have a causal relationship with this treatment: events that result in death, life-threatening events; events requiring hospitalization or prolonged hospitalization; events leading to permanent or severe disability/loss of function (significant impairment of the ability to carry out normal life functions); congenital abnormalities or birth defects; a medically important event or intervention may be required to prevent any of these outcomes.
Progression-Free Survival (PFS) Assessed by IRC（Phase III）
时间窗: From Baseline to primary completion date, about 48 months
from randomization to PD or death from any cause
次要结局
- Disease Control Rate (DCR) by investigator（Phase II）(From Baseline to primary completion date, about 48 months)
- Serious Adverse Events (SAE)（Phase III）(From Baseline to primary completion date, about 48 months)
- Overall Response Rate (ORR) Assessed by investigator（Phase II）(From Baseline to primary completion date, about 48 months)
- Duration of Overall Response (DoR) by investigator（Phase II）(From Baseline to primary completion date, about 48 months)
- Overall Survival (OS)（Phase II）(From Baseline to primary completion date, about 48 months)
- Overall Survival (OS)（Phase III）(From Baseline to primary completion date, about 48 months)
- Progression-Free Survival (PFS) Assessed by investigator（Phase III）(From Baseline to primary completion date, about 48 months)
- Overall Response Rate (ORR) Assessed by IRC and investigator（Phase III）(From Baseline to primary completion date, about 48 months)
- Progression-Free Survival (PFS) Assessed by investigator（Phase II）(From Baseline to primary completion date, about 48 months)
- Characterize the PK（Phase II）(From Baseline to primary completion date, about 48 months)
- Duration of Overall Response (DoR) by IRC and investigator（Phase III）(From Baseline to primary completion date, about 48 months)
- Disease Control Rate（DCR） by IRC and investigator（Phase III）(From Baseline to primary completion date, about 48 months)
- Adverse Events (AE) According to NCI-CTCAE v5.0（Phase III）(From Baseline to primary completion date, about 48 months)