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.
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. In order to control random allocation and allocation hiding and ensure the science and standardization of randomized controlled trials, IWRS system of Beijing Biaoji Information Technology Co., Ltd. was used for randomization. In order to ensure data multi-channel upload, safe storage, data desensitization and data sharing, as well as the accuracy of data entry and simple cleaning, the EDC system needs to be established. Beijing Biaozhi Information Technology Co., Ltd. is entrusted with the EDC system. It includes: ①EDC system; ②System supporting services: CRF annotation, eCRF establishment and testing, logic verification (logic verification plan, logic verification rule programming, logic verification rule testing), EDC training services; ③ Project management. The sample-size calculation assumed a median overall survival of 4.43 months in the control group and 7.03 months in the experimental group. The test level (α) is set as 0.05, the test efficacy (1-β) as 0.80, and the expected shedding rate is 10%. After calculating by PASS software, a total of 306 patients are expected to be enrolled, and the experimental group and control group were randomly divided by 1:1, with 153 patients in the experimental group and 153 in the control group. Descriptive statistical analysis will be used in this study. The measurement data are described by mean, standard deviation, median, lower quartile, upper quartile, minimum and maximum. Count data and rank data list frequency (component ratio) and rate. Describe the number of subjects enrolled in each group, and the number of cases dropped and eliminated. The final analysis of the study will be based on data collected by the subjects throughout the study period.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
305
Qingyihuaji Optimization Formula each bag contains: (1)Scutellaria barbata D. Don (Banzhilian); (2) Hedyotis diffusa Willd. (Sheshecao); (3) Amorphophallus rivieri Durieu (Sheliugu); (4) Amomi Fructus Rotundus (Doukou); (5) Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan); (6) Semen Coicis (Yiyiren); (7) Ganoderma lucidum (Curtis) P. Karst. (Lingzhi). One bag at a time, twice a day, rinsing with boiling water, continuous administration, oral administration in the morning and evening, every 3 weeks as a cycle.
The sensory-matched placebo was manufactured to resemble QYHJ optimized formula in appearance, color, taste, odor, packaging, labeling, and administration schedule. Each placebo sachet contained 2% QYHJ granules, 86.13% maltodextrin, 10% lactose, 1.28% caramel pigment, 0.08% lemon-yellow pigment, 0.01% sunset-yellow pigment, and 0.50% bittering agent. Participants took one 8-g sachet orally twice daily, in the morning and evening, after reconstitution with boiling water. Treatment was administered continuously, with each 3-week period defined as one study-product cycle.
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
Affiliated Hospital of Nanjing University of Traditional Chinese Medicine
Nanjing, Jiangsu, China
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
Shanghai, Shanghai Municipality, China
Overall survival (OS)
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.
Time frame: From date of randomization until the date of death from any cause, assess up to 24 months
Progression-Free Survival (PFS)
defined as the time from randomization to radiographic tumor progression or death from any cause. Subjects with no evidence of progress at the time of final analysis or who have been lost to follow-up will be truncated at the date of the last tumor evaluation.
Time frame: From date of randomization until the date of first documented progression, assessed up to 24 months
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