ChiCTR2500104706 版本V1.0 版本创建时间2025/06/22 20:55:38 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

 ChiCTR2500104706 

最近更新日期：

Date of Last Refreshed on：

 2025-06-22 20:55:31 

注册时间：

Date of Registration：

 2025-06-22 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

特瑞普利单抗联合安罗替尼治疗紫衫烷类失败的HER2阴性复发或转移性乳腺癌的Ib/II期临床试验

Public title：

A Phase Ib/II Clinical Trial of Toripalimab Plus Anlotinib in Taxane-Refractory HER2-Negative Recurrent or Metastatic Breast Cancer

注册题目简写：

English Acronym：

研究课题的正式科学名称：

特瑞普利单抗联合安罗替尼治疗紫衫烷类失败的HER2阴性复发或转移性乳腺癌的Ib/II期临床试验

Scientific title：

A Phase Ib/II Clinical Trial of Toripalimab Plus Anlotinib in Taxane-Refractory HER2-Negative Recurrent or Metastatic Breast Cancer

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

申请注册联系人：

吴静 

研究负责人：

吴静/曾晓华 

Applicant：

Jing Wu 

Study leader：

Jing Wu, Xiaohua Zeng 

申请注册联系人电话：

Applicant telephone：

 +86 177 8475 8770

研究负责人电话：

Study leader's
telephone：

+86 177 8475 8770

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

 380034326@qq.com

研究负责人电子邮件：

Study leader's E-mail：

 380034326@qq.com

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

申请注册联系人通讯地址：

重庆市沙坪坝区汉渝路181号

研究负责人通讯地址：

重庆市沙坪坝区汉渝路181号

Applicant address：

181, Hanyu Road, Shapingba District, Chongqing

Study leader's address：

181, Hanyu Road, Shapingba District, Chongqing

申请注册联系人邮政编码：

Applicant postcode：

 400030

研究负责人邮政编码：

Study leader's postcode：

 400030

申请人所在单位：

重庆大学附属肿瘤医院

Applicant's institution：

Chongqing University Cancer Hospital

研究负责人所在单位：

重庆大学附属肿瘤医院

Affiliation of the Leader：

Chongqing University Cancer Hospital

是否获伦理委员会批准：

是

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

 CZLS2025173-A

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

重庆大学附属肿瘤医院伦理委员会

Name of the ethic committee：

Ethics Committee of Chongqing University Cancer Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2025-06-06 00:00:00

伦理委员会联系人：

汤晓华

Contact Name of the ethic committee：

Xiaohua Tang

伦理委员会联系地址：

重庆市沙坪坝区汉渝路181号

Contact Address of the ethic committee：

181, Hanyu Road, Shapingba District, Chongqing

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 23 6507 5696

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 czll6545@126.com

研究实施负责（组长）单位：

重庆大学附属肿瘤医院

Primary sponsor：

Chongqing University Cancer Hospital

研究实施负责（组长）单位地址：

重庆市坪坝区汉渝路181号

Primary sponsor's address：

181, Hanyu Road, Shapingba District, Chongqing

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

重庆

市(区县)：

沙坪坝

Country：

China

Province：

Chongqing

City：

Shapingba

单位(医院)：

重庆大学附属肿瘤医院

具体地址：

重庆市沙坪坝区汉渝路181号

Institution
hospital：

Chongqing University Cancer Hospital

Address：

181, Hanyu Road, Shapingba District, Chongqing

经费或物资来源：

特瑞普利单抗(买一赠一)由上海君实生物医药科技股份有限公司资助，安罗替尼（全赠药）由正大天晴药业集团股份有限公司资助

Source(s) of funding：

"Toripalimab (semi-free) was supported by Shanghai Junshi Biosciences Co., Ltd. Anlotinib (full charity drug supply) was donated by Chia Tai Tianqing Pharmaceutical Group Co., Ltd."

研究疾病：

乳腺癌  

Target disease：

Breast cancer

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

 I期+II期 

Study phase：

1-2

研究设计：

随机平行对照 

Study design：

Parallel 

研究目的：

1、Ib期(剂量递增) 主要目的： ? 确定特瑞普利单抗联合安罗替尼在HER2阴性复发或转移性乳腺癌患者中的 II 期推荐剂量。 次要目的： ? 评估特瑞普利单抗联合安罗替尼不同给药剂量治疗HER2阴性复发或转移性乳腺癌患者的安全性； ? 评估特瑞普利单抗联合安罗替尼不同给药剂量治疗HER2阴性复发或转移性乳腺癌患者的疗效； 2、II期 主要目的: ? 评价特瑞普利单抗联合安罗替尼对比医生选择的化疗(艾立布林、长春瑞滨、卡培他滨、吉西他滨)治疗HER2阴性复发或转移性乳腺癌的无进展生存期(PFS)； 次要目的: ? 评价特瑞普利单抗联合安罗替尼对比医生选择的化疗(艾立布林、长春瑞滨、卡培他滨、吉西他滨)治疗HER2阴性复发或转移性乳腺癌的客观有效率(ORR)； ? 评价特瑞普利单抗联合安罗替尼治疗HER2阴性复发或转移性乳腺癌的临床获益率(CBR)、客观缓解持续时间(DoR)； ? 评价特瑞普利单抗联合安罗替尼对比医生选择的化疗(艾立布林、长春瑞滨、卡培他滨、吉西他滨)治疗HER2阴性复发或转移性乳腺癌的总生存期(OS)； ? 评价特瑞普利单抗联合安罗替尼对比医生选择的化疗(艾立布林、长春瑞滨、卡培他滨、吉西他滨)治疗HER2阴性复发或转移性乳腺癌的生活质量评分； 探索性目的: ? 评价患者生物样本中潜在预测性生物标志物(包括但不限于PD-L1、PD-L2表达，基因mRNA表达、DNA基因变异、TMB、肿瘤浸润淋巴细胞，CD8阳性T细胞等)与疗效(如客观缓解率、无进展生存期和总生存期)的相关性。  

Objectives of Study：

1. Phase Ib (Dose Escalation) Primary Objective ? To determine the recommended phase II dose (RP2D) of toripalimab plus anlotinib in patients with HER2-negative recurrent or metastatic breast cancer. Secondary Objectives ? To evaluate the safety of different dose levels of toripalimab combined with anlotinib. ? To assess the efficacy of different dose levels of toripalimab combined with anlotinib. 2. Phase II (Dose Expansion) Primary Objective ? To compare progression-free survival (PFS) of toripalimab plus anlotinib versus physician’s choice chemotherapy (eribulin/vinorelbine/capecitabine/gemcitabine) in HER2-negative recurrent or metastatic breast cancer. Secondary Objectives ? To compare objective response rate (ORR) between the combination therapy and chemotherapy arms. ? To evaluate clinical benefit rate (CBR) and duration of response (DoR) for toripalimab plus anlotinib. ? To compare overall survival (OS) between the combination therapy and chemotherapy arms. ? To assess quality of life (QoL) differences using validated scales (e.g., EORTC QLQ-C30). Exploratory Objectives ? To investigate correlations between potential predictive biomarkers (including but not limited to: PD-L1/PD-L2 expression, mRNA signatures, DNA variants, tumor mutational burden [TMB], tumor-infiltrating lymphocytes [TILs], CD8? T-cell density) and efficacy endpoints (ORR/PFS/OS).

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1.研究参与者或其法定代理人自愿书面签署知情同意书； 2.年龄为 18~75周岁(包含上下限)，男性或女性； 3.经细胞学或组织学诊断为HER2阴性乳腺癌(HER2 阴性需满足下列情况之一：IHC0；IHC1+；IHC2+应进一步应用原位杂交(ISH)的方法确定HER2阴性)； 4.既往经过紫衫烷类化疗药物治疗后进展的复发或转移性乳腺癌患者；允许纳入既往新辅助和/或辅助阶段使用过紫杉类药物治疗后进展的患者，但须满足紫杉烷类(新)辅助治疗结束时间距出现复发/转移间隔<=12个月，应将其算作1线治疗失败； 5.若为激素受体阳性患者，需在复发或转移阶段必须接受过内分泌治疗后进展，但原发性内分泌耐药(即术后内分泌治疗2年内进展)或ER弱表达(即ER表达在1%-10%)等研究者判定为内分泌不获益的患者除外，激素受体阳性患者CPS>=1； 6.经研究者确认或病史记录具有明确的疾病进展证据； 7.根据 RECIST1.1 标准，至少有一个可测量的靶病灶； 8.ECOG 功能状态评分 0~1 分； 9.有原发灶或转移灶存档肿瘤组织标本或新鲜组织样本可进行PDL1检测； 10.具有充分的器官和骨髓功能(可参考各临床试验中心正常值上限)：a)骨髓功能：中性粒细胞绝对值(ANC)>=1.5×10^9/L； 血小板>=100×10^9/L； 血红蛋白>=90g/L；b)肝功能：总胆红素<=1.5 倍正常值上限(ULN)； 谷丙转移酶(ALT)、谷草转移酶(AST)<=3 倍 ULN；有肝转移时 ALT、AST<=5 倍 ULN，有骨转移时，ALP<=5 倍ULN；c)肾功能：肌酐<=1.5 倍 ULN，或肌酐清除率(Ccr)>=50mL/min(根据 Cockcroft and Gault 公式)；d)凝血功能：国际标准化比 值(INR)<=1.5 倍 ULN，活化部分凝血活酶时间(APTT)<=1.5 倍ULN；e) 尿蛋白-/+，若尿蛋白>=2+，要求额外检测 24 小时尿蛋白定量，如 24 小时尿蛋白＜1g，可以入组； 11.预期生存期>=3 个月。

Inclusion criteria

1. Study participants or their legal representatives voluntarily sign an informed consent form in writing; 2. Age 18~75 years old (including upper and lower limits), male or female; 3. Cytological or histological diagnosis of HER2-negative breast cancer (HER2-negative must meet one of the following conditions: IHC0; IHC1 ; IHC2 should be further determined by in situ hybridization (ISH) to determine HER2 negative); 4. Patients with recurrent or metastatic breast cancer who have progressed after prior treatment with purple-liner chemotherapy drugs; Patients who have progressed on prior neoadjuvant and/or adjuvant taxane therapy are allowed to be included, provided that the interval between recurrence/metastasis at the end of taxane (neoadjuvant therapy) is <=12 months, which should be counted as 1st line therapy failure; 5. If the patient is hormone receptor positive, it is necessary to have progressed after receiving endocrine therapy in the relapse or metastasis stage, except for patients with primary endocrine resistance (i.e., progression within 2 years of postoperative endocrine therapy) or weak expression of ER (i.e., ER expression in 1%-10%), and patients with hormone receptor positive have a > CPS =1; 6. Clear evidence of disease progression confirmed by the investigator or documented in medical history; 7. At least one measurable target lesion according to criteria RECIST1.1; 8. ECOG functional status score of 0~1 points; 9. Archival tumor tissue specimens or fresh tissue samples from primary or metastatic lesions can be tested for PDL1; 10. Have adequate organ and bone marrow function (refer to the upper limit of normal value of each clinical trial center): a) Bone marrow function: absolute neutrophil value (ANC) >=1.5×10^9/L; platelets>=100×10^9/L; hemoglobin > = 90 g/L; b) Liver function: total bilirubin <=1.5 times the upper limit of normal (ULN); Alanine transferase (ALT), aspartate transferase (AST) <=3-fold ULN; ALT, AST<=5 times ULN in liver metastases, ALP<=5 times ULN in bone metastases; c) renal function: creatinine <=1.5 times ULN, or creatinine clearance (Ccr) >=50mL/min (according to Cockcroft and Gault formula); d) Coagulation function: international normalized ratio value (INR) <=1.5 times ULN, activated partial thromboplastin time (APTT) <=1.5 times ULN; e) Urine protein-/, if urine protein >=2, additional testing of 24-hour urine protein quantification, such as 24-hour urine protein <1g, can be enrolled; 11. Expected survival >=3 months.

排除标准：

1.存在脑干、脑膜转移、脊髓转移或压迫；活动性中枢神经系统转移。但先前治疗过的脑转移受试者(如手术、放疗)，如果治疗后临床稳定至少两周(距入组当天开始起计算)，且入组前 14 天内停用皮质类固醇激素，则允许入组；未经治疗、无症状的脑转移受试者(即没有神经系统症状，不需要皮质类固醇等治疗，且病灶<=1.0cm)可以入组； 2.既往接受过免疫治疗或抗血管生成抑制剂类药物治疗者； 3.既往高血压危象或高血压脑病病史；存在药物未能控制的高血压(收缩压＞140mmHg 和/或舒张压＞90mmHg)； 4. 入组前 6 个月内的动脉血栓、深静脉血栓病史：如肺栓塞、脑梗死、短暂性脑缺血发作、心肌梗死等，但不需要治疗的导管相关附壁血栓可以入组； 5. 显著的血管疾病(包括但不限于需要手术修复的主动脉瘤或近期动脉血栓形成)、不稳定型心绞痛、纽约心脏病协会(NYHA)分类>=Ⅲ级的心功能不全、药物无法控制的严重心律失常； 6.入组前 4 周内有重大手术、重大外伤史；不管严重程度如何，存在任何出血体质迹象或病史的受试者；在首次给药前 4 周内，出现任何出血或流血事件>= CTCAE3 级的受试者；或存在未愈合创口、骨折、胃及十二指肠活动性溃疡、溃疡性结肠炎等消化道疾病或未切除的肿瘤存在活动出血，或研究者判定的可能引起消化道出血、穿孔的其他状况； 7.存在任何活动性自身免疫病或有自身免疫病病史且预期复发(如系统性红斑狼疮、类风湿性关节炎、炎症性肠病、多发性硬化、垂体炎、血管炎等)；但不包括以下疾病：经固定剂量胰岛素治疗病情稳定的Ⅰ型糖尿病；只需接受激素替代治疗或无需进行治疗的甲状腺功能减退症；无需进行全身治疗的皮肤疾病(如湿疹，占体表 10%以下的皮疹，无眼科症状的银屑病等)； 8.有明确临床诊断为间质性肺炎，肺纤维化，药物性肺炎病史或筛选期胸部 CT 检查发现有需要治疗的活动性肺炎的证据；患有活动性肺结核(TB)的患者，正在接受抗结核治疗或者筛选前 1 年内接受过抗结核治疗； 9.不能控制的需要反复引流的胸腔积液、心包积液或腹水； 10.乙肝表面抗原阳性且 HBVDNA>=ULN 者，或丙型肝炎病毒抗体、人类免疫缺陷病毒抗体检查结果中任意一种呈阳性者； 11.妊娠期或哺乳期女性受试者；不愿或不能在本试验的整个治疗期间及试验用药品末次给药后 8 个月内采用可接受的方法进行避孕的育龄妇女(育龄妇女包括：任何有过月经初潮，以及未接受过成功的人工绝育手术[子宫切除术、双侧输卵管结扎、或双侧卵巢切除术]或未绝经)或男性受试者； 12.任何精神或认知障碍，可能会限制其对知情同意书的理解、执行； 13. 在过去3年内患有另一种恶性肿瘤者不可入组，（除外情况：接受治愈性治疗的原位宫颈癌、非黑色素瘤皮肤癌等恶性肿瘤可以入组）； 14. 研究者认为不适合参与本试验的其他情况，如依从性差等。受治愈性治疗的原位宫颈癌、非黑色素瘤皮肤癌等恶性肿瘤可以入组）； (14) 研究者认为不适合参与本试验的其他情况，如依从性差等。

Exclusion criteria：

1. Presence of brainstem, meningeal metastases, spinal cord metastases or compression; Active central nervous system metastases. However, subjects with previously treated brain metastases (e.g., surgery, radiotherapy) are allowed to be enrolled if they are clinically stable for at least two weeks after treatment (counting from the start of the day of enrollment) and corticosteroids are discontinued within 14 days prior to enrollment; Subjects with untreated, asymptomatic brain metastases (i.e., no neurological symptoms, no need for treatment such as corticosteroids, and lesion <=1.0cm) can be enrolled; 2. Those who have received immunotherapy or anti-angiogenic inhibitor drugs in the past; 3. History of previous hypertensive crisis or hypertensive encephalopathy; Presence of hypertension (systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg) that is not controlled by medication; 4. History of arterial thrombosis, deep vein thrombosis within 6 months prior to enrollment: such as pulmonary embolism, cerebral infarction, transient ischemic attack, myocardial infarction, etc., but catheter-related adherent thrombosis that does not require treatment can be enrolled; 5. Significant vascular disease (including but not limited to aortic aneurysm requiring surgical repair or recent arterial thrombosis), unstable angina, New York Heart Association (NYHA) classification >=III. cardiac insufficiency, severe arrhythmia uncontrolled by medication; 6. History of major surgery and major trauma within 4 weeks prior to enrollment; Subjects with any signs or history of bleeding constitution, regardless of severity; Subjects with any bleeding or bleeding event within 4 weeks prior to the first dose >= CTCAE3 grade; or the presence of unhealed wounds, fractures, active gastric and duodenal ulcers, ulcerative colitis and other digestive tract diseases or unresected tumors with active bleeding, or other conditions that may cause gastrointestinal bleeding and perforation as judged by the investigator; 7. Presence of any active autoimmune disease or history of autoimmune disease with expected recurrence (such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, hypophysitis, vasculitis, etc.); However, the following diseases are excluded: stable type I diabetes mellitus treated with fixed-dose insulin; Hypothyroidism requiring only hormone replacement therapy or no treatment required; Skin diseases that do not require systemic treatment (such as eczema, rash that occupies less than 10% of the body surface, psoriasis without ophthalmic symptoms, etc.); 8. Have a clear clinical diagnosis of interstitial pneumonia, pulmonary fibrosis, history of drug-induced pneumonia or evidence of active pneumonia requiring treatment on chest CT examination during the screening period; Patients with active pulmonary tuberculosis (TB), who are receiving anti-tuberculosis therapy or have received anti-tuberculosis therapy within 1 year prior to screening; 9. Uncontrollable pleural effusion, pericardial effusion or ascites that require repeated drainage; 10. Those who are positive for hepatitis B surface antigen and HBVDNA>=ULN, or those who are positive for hepatitis C virus antibody and human immunodeficiency virus antibody; 11. Pregnant or lactating female subjects; Women of childbearing potential who are unwilling or unable to use an acceptable method of contraception throughout the treatment period of this trial and for 8 months after the last dose of the investigational drug product (women of childbearing potential include: any person who has had menarche, and who has not undergone successful artificial sterilization [hysterectomy, bilateral tubal ligation, or bilateral oophorectomy] or is not postmenopausal) or male subjects; 12. Any mental or cognitive impairment that may limit their understanding and execution of the informed consent form; 13. Those who have another malignant tumor in the past 3 years are not eligible for enrollment (exceptions: malignant tumors such as cervical cancer in situ and non-melanoma skin cancer that have received curative treatment can be enrolled); 14. Other conditions that the investigator considers unsuitable for participating in this trial, such as poor compliance, etc.

研究实施时间：

Study execute time：

从 From 2025-07-01 00:00:00至 To 2027-12-31 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2025-07-01 00:00:00 至 To 2027-12-31 00:00:00

干预措施：

Interventions：

组别：

试验组（Ib期研究）-单臂试验

样本量：

 9

Group：

Experimental group (phase Ib study) - single-arm trial

Sample size：

干预措施：

安罗替尼递增起始剂量为8mg，从低剂量组向高剂量组逐级递增。计划递增剂量分别为 8mg、10mg、12mg，特瑞普利单抗为固定剂量240mg，不进行剂量递增。每个剂量组第 1 例研究参与者和第 2 例研究参与者的首次给药时间至少间隔 24 小时。每个剂量组依据剂量限毒性(DLT) 评估规则并采用贝叶斯最优区间(BOIN)模型规则来决定是否终止、改变或继续剂量递增/递减。

干预措施代码：

Intervention：

The starting dose of anlotinib is 8 mg, and the dose is escalated from the low-dose group to the high-dose group. The planned escalating doses are 8mg, 10mg, and 12mg, respectively, and toripalimab is a fixed dose of 240mg, with no dose escalation. The first dose was given at least 24 hours apart in each dose group for study participants in 1 and 2 study participants. Each dose group was determined to terminate, change, or continue dose escalation/de-escalation according to the dose-limiting toxicity (DLT) evaluation rules and the Bayesian optimal interval (BOIN) model rule.

Intervention code：

组别：

试验组 （II期研究）-随机对照试验

样本量：

 45

Group：

Experimental group (phase II study) - randomized controlled trial

Sample size：

干预措施：

1.特瑞普利单抗注射液： 剂型：无菌水针剂型 240mg/6ml/瓶； 用法：240mg，静脉滴注第1天，每21天为一周期； 2.盐酸安罗替尼胶囊： 剂型：12mg，10mg，8mg； 用法：12mg或10mg或8mg 每日1次，连续口服 2 周停 1 周，每21天为一周期，用 药期间如出现漏服，确认距下次用药时间短于 12 小时，则不再补服。

干预措施代码：

Intervention：

1. Toripalimab injection: Dosage form: sterile water injection dosage form 240mg/6ml/bottle; Usage: 240mg, intravenous infusion on the first day, every 21 days for a cycle; 2. Anlotinib hydrochloride capsules: Dosage form: 12mg, 10mg, 8mg; Usage: 12mg or 10mg or 8mg once a day, continuous oral administration for 2 weeks and 1 week, every 21 days as a cycle, use If there is a missed dose during the drug period, and it is confirmed that the next dose is less than 12 hours before the next dose, the follow-up dose will not be repeated.

Intervention code：

组别：

对照组（ II期研究）-随机对照试验

样本量：

 45

Group：

Control group (phase II study) - randomized controlled trial

Sample size：

干预措施：

1.甲磺酸艾立布林注射液 剂型：无色的澄明溶液 2ml:1mg/支； 用法：1.4mg/m^2，2-5分钟内静脉推注，第1天和第8天给药1次，每21天为一周期； 2.酒石酸长春瑞滨注射液 剂型：本品为无色至微黄色澄明液体； 用法：25mg/m^2，第1天和第8天给药1次，每21天为一周期； 3.卡培他滨片 剂型：0.15g：双凸、长方形、浅桃色包衣片，除去包衣显白色；0.5g：双凸、长方形、桃色包衣片，除去包衣显白色； 用法：1000mg/m^2，口服，1天2次，第1天至第14天连续给药，停药7天，每21天为一周期； 4.注射用盐酸吉西他滨 剂型：白色或类白色粉末或疏松块状物 0.2g;1.0g； 用法：1000mg/m^2，静脉滴注30分钟，第1天和第8天给药1次，每21天为一周期。

干预措施代码：

Intervention：

1. Eribulin mesylate injection Dosage form: colorless clear solution 2ml: 1mg/piece; Usage: 1.4mg/m^2, intravenous bolus within 2-5 minutes, administered once on day 1 and day 8, every 21 days for a cycle; 2. Vinorelbine tartrate injection Dosage form: This product is a colorless to yellowish clear liquid; Usage: 25mg/m^2, administered once on day 1 and day 8, every 21 days for a cycle; 3. Capecitabine tablets Dosage form: 0.15g: biconvex, rectangular, light peach-colored coated tablets, white after coating; 0.5g: biconvex, rectangular, peach-colored coated tablets, white without coating; Usage: 1000mg/m^2, oral, 2 times a day, continuous administration from day 1 to day 14, stop drug for 7 days, every 21 days for a cycle; 4. Gemcitabine hydrochloride for injection Dosage form: white or off-white powder or loose lump 0.2g; 1.0g; Usage: 1000mg/m^2, intravenous infusion for 30 minutes, administered once on day 1 and day 8, every 21 days for a cycle.

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 重庆 

市(区县)：

 沙坪坝 

Country：

China

Province：

Chongqing

City：

Shapingba

单位(医院)：

 重庆大学附属肿瘤医院 

单位级别：

 三级甲等 

Institution
hospital：

Chongqing University Cancer Hospital

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

无进展生存期

指标类型：

主要指标

Outcome：

Progression-free survival(PFS)

Type：

Primary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

临床获益率

指标类型：

次要指标

Outcome：

Clinical benefit rate(CBR)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

肿瘤有效率

指标类型：

次要指标

Outcome：

Objective response rate(ORR)

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

总生存期

指标类型：

次要指标

Outcome：

Overall survival

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

安全性指标

指标类型：

次要指标

Outcome：

Safety index

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

客观缓解持续时间

指标类型：

次要指标

Outcome：

Duration of objective response

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

生活质量

指标类型：

次要指标

Outcome：

Quality of life

Type：

Secondary indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

指标中文名：

潜在预测性生物标志物(包括但不限于PD-L1、PD-L2表达，基因mRNA表达、DNA基因变异、TMB、肿瘤浸润淋巴细胞，CD8阳性T细胞等)与疗效(如客观缓解率、无进展生存期和总生存期)的相关性

指标类型：

附加指标

Outcome：

The correlation between potential predictive biomarkers (including but not limited to PD-L1 and PD-L2 expressions, gene mRNA expression, DNA gene variation, TMB, tumor-infiltrating lymphocytes, CD8 positive T cells, etc.) and therapeutic effects (such as objective response rate, progression-free survival and overall survival)

Type：

Additional indicator

测量时间点：

测量方法：

Measure time point of outcome：

Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

血液

组织：

Sample Name：

Blood

Tissue：

人体标本去向

 使用后销毁  

说明

Fate of sample：

Destruction after use  

Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 75 岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

由统计学相关人员使用随机数生成器分配受试者

Randomization Procedure (please state who generates the random number sequence and by what method)：

The subjects were assigned by experts related to statistics using a random number generator

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

公开/Public

盲法：

无

Blinding：

None

试验完成后的统计结果（上传文件）：

Calculated Results after
the Study Completed(upload file)：

是否共享原始数据：

IPD sharing

否No

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

无

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

None

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

病历记录表

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

CRF

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2025-06-22 20:55:31