Clinical Efficacy of QingyiHuaji Optimized Formula Combined With Standard Chemotherapy in the Treatment of Advanced Pancreatic Cancer: a Prospective, Multicenter, Randomized Controlled Clinical Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 305
- 试验地点
- 4
- 主要终点
- Overall survival (OS)
研究概览
简要总结
This prospective, multicenter, randomized, double-blind, placebo-controlled phase 3 trial included adults with histologically or cytologically confirmed stage IV pancreatic ductal adenocarcinoma who were eligible for gemcitabine-based first-line combination chemotherapy according to the 2022 NCCN guidelines and had an estimated survival of more than 3 months.
The planned sample size was 306 participants. A total of 305 participants were enrolled and randomly assigned in a 1:1 ratio to receive either Qingyi Huaji (QYHJ) optimized formula combined with standard treatment or a matched placebo combined with the same standard treatment.
The primary outcome was overall survival, defined as the time from randomization to death from any cause and assessed for up to 24 months. Secondary outcomes included progression-free survival, quality of life, safety, and improvement in traditional Chinese medicine symptoms. Traditional Chinese medicine syndrome classification was recorded for exploratory analyses but was not an eligibility requirement.
The hypothesis was that adding QYHJ optimized formula to standard chemotherapy would prolong overall survival without causing an unacceptable increase in toxicity. The study was conducted from April 17, 2023, through December 30, 2025.
详细描述
Pancreatic cancer is a digestive tract tumor with high malignancy and poor prognosis. The overall 5-year survival rate of early stage patients after surgery is less than 9%, while the median survival time of advanced stage patients is only 3-6 months. According to statistics, in 2020, there were about 420,000 new cases of pancreatic cancer worldwide, and about 410,000 deaths. In China, with the improvement of people's living standards and the progress of population aging, the incidence of pancreatic cancer is rising year by year, ranking 7th among men, and the mortality rate is 6th among men and 8th among women.
Due to its deep anatomical location, lack of typical clinical symptoms, and easy invasion and metastasis of tumors, pancreatic cancer is difficult to be detected in the early stage. More than 80% of patients are in local advanced stage or have distant metastasis at the time of diagnosis, thus losing the opportunity for radical surgery. Currently gemcitabine combined with albumin-binding paclitaxel regimen or FOLFIRINOX (fluorouracil, calcium leucovorin, irinotecan, oxaliplatin) regimen is the first-line chemotherapy regimen for pancreatic cancer.
However, pancreatic cancer has poor sensitivity to chemical and radiotherapy, and there has been little progress in targeted therapy and immunotherapy, resulting in no significant improvement in the survival rate of pancreatic cancer in recent decades. Meanwhile, the curative effect of other common tumors has made rapid progress. It is estimated by the NCI in the United States that if there is no breakthrough in the treatment of pancreatic cancer, pancreatic cancer will become the second largest tumor killer in human by 2030.
After nearly 20 years of dedicated research, the research team of Fudan University Shanghai cancer center, has carried out the integrated treatment mode of traditional Chinese and Western medicine to improve the survival of advanced pancreatic cancer patients, making the median OS of advanced pancreatic cancer patients reach the world leading level by 45% longer than that of chemotherapy alone, and the 3-year, 5-year survival rate reaches 15% and 6.2%, respectively. However, for patients with stage IV pancreatic ductal adenocarcinoma, improving survival and quality of life remains an important clinical need.
The results suggest that QingyiHuayi formula has certain anti-tumor effect in advanced pancreatic cancer, and the combination of Qingyi Huayi formula with chemotherapy can prolong the survival period of patients, improve the clinical benefit rate, and may improve the therapeutic effective rate, without increasing the adverse reaction of radiotherapy and chemotherapy. The pathogenesis theory of cancer toxins puts forward that the pathogenesis of cancer toxins should be the core of syndrome differentiation, which solves the complicated and difficult problem of TCM tumor classification by disease differentiation. Four key points of clinical identification of cancer toxins pathogenesis were put forward to achieve the breakthrough of cancer virus identification and diagnosis technology bottleneck. To establish anti-cancer and detoxification treatment methods and classification of anti-cancer and detoxification Chinese medicines, and promote the clinical precision treatment and drug use of TCM tumors. Therefore, Qingyihuayi formula is a safe and effective treatment plan for advanced pancreatic cancer. After optimization, more clinical studies are needed to clarify the value of Qingyihuayi formula in the treatment of advanced pancreatic cancer and find more target groups of benefits.
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
- Double (Participant, Investigator)
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
- •Histologically or cytologically confirmed Stage IV pancreatic ductal adenocarcinoma.
- •The expected survival time is >3 months;
- •Patients meet the standard treatment of gemcitabine - based first-line combination therapy recommended by the 2022 edition of the NCCN Pancreatic Cancer Guidelines;
- •Age above 18 years old and ≤75 years old;
- •ECOG physical state score 0-1;
- •Patients own adequate organ and bone marrow function, defined as neutrophils ≥1,500/ul, hemoglobin ≥ 8.0gm /dL, platelets ≥80,000/uL, serum creatinine < 2.0 mg/dL, bilirubin < 1.5 mg/dL, alanine aminotransferase < 3 times the upper limit of normal; If obstructive jaundice was allowed to enter the study after desicrin treatment, liver function markers were moderately relaxed to bilirubin < 2.5 mg/dL and alanine aminotransferase < 5 times the upper limit of normal.
- •Patients must have measurable lesions that meet the RECIST1.1 evaluation criteria. Bone scan abnormalities alone or osteolytic changes shown on plain radiographs cannot be measurable lesions, but can be evaluated in conjunction with bone scan abnormalities. Simple osteogenic bone metastases, pleural or peritoneal exudation, and radiation injury could not be considered as measurable lesions.
- •Patients who have not received "Qingyi Huayji Optimized formula " before (patients who have taken medicine for less than 2 weeks can be included at the discretion of the researchers) and who have received other traditional Chinese medicine treatment before must stop taking medicine 1 week before this study.
- •Female subjects of reproductive age must undergo a negative pregnancy test within 2 weeks prior to study drug initiation and be willing to use a medically approved highly effective contraceptive (e.g., intrauterine device, contraceptive or condom) during the study period and within 3 months after the last study drug administration; Male subjects with partners of women of reproductive age should agree to use effective contraceptive methods during the study period and within 3 months after the last study administration;
- •Patients is expected to possess good compliance, can understand and sign written informed consent, and willing to cooperate with the collection of TCM syndrome information;
- •SIRI value ≥0.8; SIRI = N × M/L, N, M, and L represent peripheral blood neutrophil, monocyte, and lymphocyte counts, respectively.
排除标准
- •Patients with ECOG score ≥2, who could not tolerate any antitumor therapy, or who could only receive the best supportive treatment were not considered for inclusion in this study.
- •The expected survival time < 3 months.
- •Other serious diseases or conditions, including deep vein thrombosis of the lower extremities, congestive heart failure (New York Heart Association Grade III or IV), unstable angina, etc.
- •Patients with co-infection requiring intravenous antibiotic treatment.
- •Pregnant or lactating women. Women of childbearing age who were unwilling or unable to use an acceptable method of contraception throughout the treatment period of this trial and within 12 weeks after the final administration of the study drug.
- •Known pancreatic neuroendocrine tumors, acinar cell carcinoma, intraductal papillary tumors and other types of pancreatic tumors.
- •Past or concurrent cancers with a primary focus or histologically distinct from pancreatic cancer, except cervical carcinoma in situ, treated basal cell carcinoma, and superficial bladder tumors (Ta, Tis & T1). Any cancer that had been cured for more than 3 years prior to inclusion was admitted.
- •Those who are known to be allergic to components of Qingyihuaji optimized formula.
- •Unable to swallow Traditional Chinese medicine or untreated malabsorption syndrome, or unwilling to take Traditional Chinese medicine.
研究组 & 干预措施
Placebo group
placebo combined with standard treatment
干预措施: Matched placebo (Drug)
Experimental group
QingyiHuaji optimized formula combined with standard treatment
干预措施: QingyiHuaji optimized formula (Drug)
结局指标
主要结局
Overall survival (OS)
时间窗: From date of randomization until the date of death from any cause, assess up to 24 months
defined as the time from randomization to death from any cause. Subjects who are still alive at the time of final analysis or who have been lost to follow-up will be truncated at the last date of known survival.
次要结局
- Disease Free Survival(From date of randomization until the date of first documented progression, assessed up to 24 months)
- Progression-Free Survival (PFS)(From date of randomization until the date of first documented progression, assessed up to 24 months)