Oncolytic Virus(H101) Combined With Camrelizumab for Recurrent Cervical Cancer: a Prospective, Multicenter Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 55
- 试验地点
- 4
- 主要终点
- ORR(Objective Response Rate)
研究概览
简要总结
There is no standard treatment for recurrent cervical cancer that progresses or persists after first-line treatment. The objective response rate of anti-PD-1 antibody treatment is about 15%. The purpose of this study was to evaluate whether the regimen could improve the objective response rate by intratumoral injection of oncolytic virus(recombinant human adenovirus type 5 injection, H101) combined with anti-PD-1 antibody(camrelizumab).
详细描述
- Main research purpose To evaluate the efficacy of H101 combined with camrelizumab in patients with incurable recurrent cervical cancer.
- Secondary research purpose To evaluate other curative effects of H101 combined with camrelizumab in patients with incurable recurrent cervical cancer.
To evaluate the safety of H101 combined with camrelizumab in patients with incurable recurrent cervical cancer. 3. Purpose of Exploratory Research To explore the changes of tumor microenvironment before and after H101 injection and the mechanism of action in combination with PD-1, and to accurately screen the beneficiaries based on molecular expression. 4. Overall experimental design This study is a multicenter, prospective, clinical study to investigate the efficacy and safety of H101 combined with camrelizumab in the treatment of incurable recurrent cervical cancer patients. It is expected that 55 subjects will be enrolled.
The study was divided into 5 phases: screening period, baseline period, treatment period, and follow-up period. Patients with recurrent cervical cancer who were eligible for inclusion and were incurable by previous first-line treatment were screened. During the follow-up period, follow-up was conducted every 1 month for at least 2 years. 5. Subject population The target population of this study was patients with recurrent cervical squamous cell carcinoma/adenocarcinoma/adenosquamous carcinoma who were incurable after first-line therapy. 6. Treatment allocation All subjects enrolled in this study received H101 combined with camrelizumab. 7. Drug dosage and administration in the trial Dosing regimen: H101 + camrelizumab. 1) H101: 1 lesion was selected for intratumoral injection. Intratumoral injection of H101 was used on the 1st and 4th day of each cycle, repeated once in 3 weeks. H101 dosage: Tumor maximum diameter ≤5 cm, 1.5×10^12vp (3 injections) on day 1 and 1.0×10^12vp (2 injections) on day 4.
Tumor maximum diameter >5cm but ≤10cm, 3.0×10^12vp (6 injections) on day 1, 2.0×10^12vp (4 injections) on day 4.
Tumor maximum diameter >10cm, 4.5×10^12vp (9 injections) on day 1 and 3.0×10^12vp (6 injections) on day 4.
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 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •All of the following criteria must be met for inclusion:
- •Participants voluntarily participated in this study and signed the informed consent;
- •18-80 years old;
- •Cervical squamous cell carcinoma/adenocarcinoma/adenosquamous carcinoma;
- •Participants with incurable recurrence after first-line treatment or participants with incurable recurrence within the irradiation field;
- •At least one lesion that meets RICIST 1.1 criteria can be evaluated and can be injected intratumorally;
- •ECOG score 0-2 points;
- •Expected survival > 3 months;
- •Women of childbearing age must undergo a pregnancy test (serum or urine) before enrollment, and the result is negative, and they are willing to use appropriate methods of contraception during the trial;
- •Those who can tolerate and comply with the trial protocol, as determined by the investigator.
排除标准
- •Those who have one of the following conditions should be excluded and cannot be selected:
- •There is an infection at the intended injection site;
- •Liver cirrhosis, decompensated liver disease;
- •Have a history of immunodeficiency, including HIV positive or other acquired congenital immunodeficiency diseases;
- •Chronic renal insufficiency and renal failure;
- •Combined with other malignant tumor patients who still need treatment and/or newly diagnosed within 5 years;
- •Myocardial infarction, severe arrhythmia and ≥ grade 2 congestive heart failure (New York Heart Association (NYHA) classification);
- •Complications, need to take drugs with serious liver and kidney damage during treatment, such as tuberculosis;
- •Previous use of anti-PD-1 drugs or oncolytic viruses;
- •Patients who cannot understand the experimental content and cannot cooperate and those who refuse to sign the informed consent;
- •Those with concomitant diseases or other special conditions that seriously endanger the safety of patients or affect the completion of the study.
研究组 & 干预措施
Recombinant human adenovirus type 5+ Camrelizumab
Recombinant human adenovirus type 5: one lesion was selected for intratumoral injection.Intratumoral injection of H101 was performed on day 1 and day 4 of each cycle, and was repeated once every 3 weeks. H101 dose:
① Tumor maximum diameter ≤5cm, 1.5×10^12vp (3 injections) on day 1, 1.0×10^12vp (2 injections) on day 4.
② Tumor maximum diameter >5cm but ≤10cm, 3.0×10^12vp (6 injections) on day 1 and 2.0×10^12vp (4 injections) on day 4.
③ Tumor maximum diameter >10cm, 4.5×10^12vp (9 injections) on day 1 and 3.0×10^12vp (6 injections) on day 4.
H101 intratumoral injection until the tumor is completely regressed to stop the drug, but not more than 5 cycles at most.
Camrelizumab: administered after H101 on day 1 of each cycle and repeated for 3 weeks. Camrelizumab dose: 200 mg IV.
干预措施: Recombinant human adenovirus type 5＋Camrelizumab (Drug)
结局指标
主要结局
ORR(Objective Response Rate)
时间窗: 2 years
The proportion of CR(complete response) and PR(partial response) in all patients.
次要结局
- PFS(Progression Free Survival)(2 years)
- DCR(Disease Control Rate)(2 years)
- OS(Overall Survival)(2 years)