A Single-arm, Multicenter, Phase II Study of RC48 Plus Platinum With or Without Bevacizumab in the Treatment of HER-2 Expression Platinum-Sensitive Recurrent Ovarian Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy, safety, and quality of life scores of patients with HER2-expressing platinum-sensitive recurrent epithelial ovarian cancer treated with the combination therapy regimen of RC48 plus platinum with or without bevacizumab.
详细描述
This study set up a safety introduction period, during which the first 6 subjects who were initially enrolled in the study will slowly undergo safety monitoring. Each patient received RC48 [2.5 mg/kg, Q3W]+carboplatin (AUC5 d1 q3w) ± bevacizumab(7.5-15mg/kg d1 q3w) treatment. The monitoring time window is within 28 days after receiving the study drug treatment for the first time. If ≥ 2 dose limited toxicity (DLT) cases were observed in the first 6 subjects, and after evaluation by the research team, it was found that the toxicity was related to treatment with RC48, the initial dose of RC48 treatment for subsequent enrolled patients was adjusted to 2.0mg/kg, Q3W.
Treatment period: RC48+carboplatin ± bevacizumab, repeated every three weeks for a total of 6 cycles； Maintenance period: RC48± bevacizumab (if combined with bevacizumab during the treatment period, maintain treatment with RC48 in combination with bevacizumab; if not used during the treatment period, maintain treatment with RC48 monotherapy). Maintenance duration: Until disease progression or intolerable toxicity occurs, the longest duration of RC48 is 6 months (8 cycles).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female subjects aged from 18 to 75 years old;
- •Pathology confirmed the diagnosis of primary epithelial ovarian/fallopian tube/peritoneal carcinoma;
- •Previous treatment lines ≥1 and ≤4, first-line treatment may include maintenance therapy after complete clinical or pathological response;Previously not receiving targeted HER2 drug therapy (including monoclonal antibodies and ADC drugs)
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at trial entry;
- •Disease must be measurable by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1);
- •Estimated life expectancy of more than 3 months;
- •Local laboratory confirmed HER2 expression: IHC 1+, 2+, or 3+; Subjects were able to provide samples of the primary or metastatic site of the tumor for HER2 detection（Paraffin blocks, paraffin embedded sections or fresh tissue sections ）
- •Adequate haematological, hepatic and renal functions defined by the protocol;
- •Negative blood pregnancy test at Screening for women of childbearing potential; Highly effective contraception for female subjects if the risk of conception exists;
排除标准
- •The pathological type is non epithelial ovarian/fallopian tube/peritoneal cancer or metastatic ovarian cancer;
- •The patient has ≥ grade 2 peripheral neuropathy;
- •Patients with active bleeding or pathological conditions with high risk of bleeding, such as known hemorrhagic diseases, coagulation disorders, or tumors involving large blood vessels;
- •Suffering from central nervous system metastasis and/or cancerous meningitis. Except for stable brain metastases; 5.The toxicity caused by previous anti-tumor treatments has not yet recovered to CTCAE (version 5.0) level 0-1 (excluding 2nd degree hair loss);
- •Patients who require parenteral hydration or nutrition and have evidence of partial intestinal obstruction or perforation;
- •Except for patients with primary endometrial cancer or a history of primary endometrial cancer, unless all of the following conditions are met: stage not greater than I-B stage; No more than superficial muscle infiltration, no vascular or lymphatic infiltration; No poorly differentiated subtypes, including papillary fluid, clear cells, or other FIGO grade 3 lesions;
- •For patients undergoing cell reduction surgery before treatment, if combined with bevacizumab, they must wait for at least 28 days before starting the treatment with bevacizumab;
- •Have undergone major surgery within 4 weeks prior to the start of study administration and have not fully recovered;
- •A large amount of pleural or ascitic fluid accompanied by clinical symptoms or requiring symptomatic treatment;
- •Within 30 days of initial medication or expected to receive attenuated live vaccines during the study period;
- •Serious arterial/venous thrombotic events or cardiovascular and cerebrovascular accidents that occurred within one year prior to drug administration were studied;
- •There are systemic diseases that have not been controlled stably according to the judgment of the researcher, including diabetes, liver cirrhosis (Child Pugh Class B or C), interstitial pneumonia, obstructive pulmonary disease, etc;
- •Clinically significant cardiovascular disease patients(According to the specific requirements of the plan);
- •Individuals with active autoimmune diseases or immunodeficiency, or a history of the aforementioned conditions, including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, rheumatoid arthritis, inflammatory bowel disease, pituitary inflammation, vasculitis, nephritis, etc., shall not be included. The following exceptions apply: Patients with a history of autoimmune hypothyroidism who have received thyroid hormone replacement therapy may be included in the study. Patients with type 1 diabetes whose blood sugar can be controlled after treatment with insulin administration scheme can participate in this study;
- •Subjects with a history of other malignant tumors within five years (excluding complete treatment for in situ cervical cancer, basal cell carcinoma, or squamous cell carcinoma skin cancer);
- •Patients with congenital or acquired immune deficiency, such as human immunodeficiency virus (HIV) infection, active hepatitis B (HBV DNA ≥ 2000 IU / ml), hepatitis C (HCV antibody positive and HCV-RNA higher than the detection limit of the analytical method), or co infection of hepatitis B and hepatitis C;
- •Severe infection (e.g. need for intravenous antibiotics, antifungal or antiviral drugs) occurred within 4 weeks before the first administration, or fever (>38.5%) of unknown reason occurred during the screening period/before the first administration；
- •Currently participating in intervention clinical research treatment, or receiving other investigational drugs or research instruments within 4 weeks prior to the first administration; Not fully recovered from toxicity and/or complications caused by any intervention measures prior to initial administration (i.e. ≤ level 1 or reaching baseline, excluding fatigue or hair loss);
- •Has a clear history of allergies and may have potential allergies or intolerance to the investigational drug and its similar biological agents;
- •Individuals with a history of abuse of psychotropic substances who are unable to quit or have mental disorders;
研究组 & 干预措施
RC48+carboplatin±bevacizumab
RC48 (2.5mg/kg iv on d1 , every 21d for 6 cycles) + Carboplatin (AUC5 iv on d1 every 21d for 6 cycles)±Bevacizumab (7.5-15mg/kg iv on d1 every 21d for 6 cycles) for treatment followed by RC48 (2.5mg/kg iv on d1 , every 21d for 8 cycles)±Bevacizumab (7.5-15mg/kg iv on d1 every 21d for progress ) maintenance therapy.
干预措施: RC48+carboplatin±bevacizumab (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Up to approximately 2 years
PFS is defined as time (in months) from date of randomization to the date of the first documentation of objective progressive disease (PD) or death due to any cause in the absence of documented PD (whichever occurs first). PFS will be determined according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) based on investigator response assessment.
次要结局
- Objective Response Rate（ORR）(Up to approximately 2 years)
- Disease Control Rate (DCR)(Up to approximately 2 years)
- Number of Participants With Adverse Events (AEs)(Up to approximately 2 years)
- Overall Survival（OS）(Up to approximately 2 years)
研究者
Hong Zheng
M.D.
Peking University Cancer Hospital & Institute