Yishen Qutong Granules vs. Simulant Combined With Neoadjuvant Chemoradiotherapy or Chemoimmunotherapy in the Treatment of Locally Advanced Esophageal Cancer: A Multicenter, Prospective, Double-Blind, Randomized Controlled Trial Protocol
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 536
- 试验地点
- 1
- 主要终点
- clinical benefit rate (CBR)
研究概览
简要总结
Esophageal cancer is a high - incidence cancer type in China, characterized by high incidence, high mortality, and low survival rates. Over 90% of esophageal cancer cases in China are squamous cell carcinoma, while in Western countries, approximately 80% are adenocarcinomas. Current international guidelines, including those of the NCCN and CSCO, are not entirely suitable for the diagnosis and treatment of esophageal cancer in the Chinese context. In recent years, although the 5 - year survival rate for esophageal cancer has improved, significant challenges remain, such as severe side effects during chemoradiotherapy and targeted - immunotherapy, decreased patient tolerance and quality of life, and even interruption of treatment.
To leverage the synergistic role of traditional Chinese medicine (TCM) in the treatment of major diseases, this study, which builds on previous research, is founded on the theory of "reinforcing healthy qi to strengthen the body, removing toxins, and resolving stasis." It aims to conduct a multicenter, randomized, controlled clinical trial of the TCM formula Yishen Qutong Granules, designed to reinforce healthy qi to strengthen the body and remove toxins, in combination with neoadjuvant concurrent therapy for locally advanced esophageal squamous cell carcinoma. The study will enroll 268 patients (1:1 ratio) with locally advanced esophageal squamous cell carcinoma (cTNM stage III - IVa) who are expected to undergo neoadjuvant concurrent therapy and are potentially resectable. On the basis of conventional Western medical treatment, the treatment group will be administered the patented TCM formula Yishen Qutong Granules orally, while the control group will receive a Yishen Qutong Simulated Granules orally.
The primary outcome measure will be the clinical benefit rate (CBR, CBR = CR + PR + SD), with secondary outcomes including pathological response rate (mPR), R0 resection rate, and TCM syndrome symptom score. The study aims to establish an objective evaluation system for the efficacy and safety of combined treatment based on the integration of disease and syndrome differentiation. It will also elucidate the mechanisms underlying the therapeutic effects of Yishen Qutong Granules.
详细描述
This study is a randomized, double-blind, placebo-controlled clinical trial. The objective is to verify the efficacy and safety of Yishen Qutong Granules, a traditional Chinese medicine (TCM) for reinforcing healthy qi to strengthen the body and remove toxins, in combination with neoadjuvant concurrent chemoradiotherapy or neoadjuvant concurrent chemoimmunotherapy for locally advanced esophageal cancer that is expected to be resectable.
Patients will be recruited from the Cancer Hospital of the Chinese Academy of Medical Sciences and other collaborating clinical units involved in this project. The study will include two cohorts:
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Patients undergoing neoadjuvant concurrent chemoradiotherapy:
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A total of 268 patients with locally advanced esophageal cancer who are expected to undergo neoadjuvant concurrent chemoradiotherapy will be recruited. They will be randomly assigned in a 1:1 ratio to the treatment group and the control group, with 134 patients in each group.
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The treatment group will receive neoadjuvant concurrent chemoradiotherapy (radiotherapy + albumin-bound paclitaxel + cisplatin) and will be administered Yishen Qutong Granules concurrently with the chemoradiotherapy, at a dose of 10g per dose, three times daily (Tid).
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The control group will receive neoadjuvant concurrent chemoradiotherapy combined with a placebo (1/10 the dose of Yishen Qutong Granules), with the same timing, dosage, and duration of administration.
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The primary efficacy endpoint is the clinical benefit rate (CBR = CR + PR + SD) after neoadjuvant treatment.
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Secondary endpoints include the pathological response rate (mPR), R0 resection rate, incidence of radiation esophagitis, pain levels caused by radiation esophagitis, and TCM syndrome symptom scores.
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Follow-up will be conducted every three months for a total of eight times (over two years), during which the progression-free survival (PFS) of patients will be recorded.
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Patients undergoing neoadjuvant chemotherapy combined with immunotherapy:
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients met the diagnostic criteria of expected resectable stage III-IVa esophageal cancer, and esophageal squamous cell carcinoma was confirmed by pathology. The diagnostic criteria refered to the guidelines for the diagnosis and treatment of esophageal cancer (2018 edition). Staging criteria: UICC/AJCC TNM staging system (8th edition, 2017) was used.
- •patients had not received previous treatment and planned to receive neoadjuvant simultaneous radiotherapy (radiotherapy + platinum in combination with albumin-paclitaxel), or proposed neoadjuvant chemotherapy in combination with immunopharmaceuticals (Immunotherapy reference 2024 CSCO Esophageal Cancer Diagnosis and Treatment Guidelines + platinum in combination with albumin-paclitaxel)
- •In accordance with the syndrome type of positive deficiency and toxin stasis (kidney deficiency and deficiency syndrome + blood stasis and toxin stagnation syndrome), that is, at least one main symptom + two secondary symptoms in each syndrome scale;
- •Karnofsky Performance Scale (KPS) ≥70; (5)18 ≤ age ≤ 80 ;
- •(6) Patients who agreeed to participate in this study and sign the informed consent form.
排除标准
- •①Yishen Qutong Granules Comparison Simulator Cooperative Neoadjuvant Synchronized Radiotherapy Group: those who have contraindications to radiotherapy such as esophageal fistula or those who are allergic to chemotherapeutic drugs; ②Yishen Qutong Granules Comparison Simulator Cooperative Neoadjuvant Chemotherapy Combined with Immunotherapy Drugs Group: those who have contraindications to chemotherapy and immunotherapy or those who are allergic to the drugs;
- •patients with a history of other tumors, cardiovascular and cerebrovascular diseases, liver and kidney function damage, hematopoietic system diseases, and other serious diseases;
- •patients with mental disorders;
- •patients during pregnancy and lactation;
- •patients allergic to traditional Chinese medicine used in this study.
研究组 & 干预措施
Chemoradiotherapy TCM Treatment Group
On the basis of neoadjuvant concurrent chemoradiotherapy (primarily based on a combination of Paclitaxel/Albumin-bound Paclitaxel, Cisplatin, and Radiotherapy), 10g/bag of Yishen Qutong Granules, 1 sachet per time, Tid, the administration cycle is the same as that of neoadjuvant concurrent chemoradiotherapy
干预措施: Yishen Qutong Granules (Drug)
Chemoradiotherapy TCM Simulant Group
On the basis of neoadjuvant concurrent chemoradiotherapy (primarily based on a combination of Paclitaxel/Albumin-bound Paclitaxel, Cisplatin, and Radiotherapy), 10g/bag of Yishen Qutong Granules (Yishen Qutong Simulant Granules, 1/10 Yishen Qutong Granules), 1 sachet per time, Tid, the administration cycle is the same as that of neoadjuvant concurrent chemoradiotherapy
干预措施: Yishen Qutong Simulant Granules (Drug)
Chemoimmunotherapy TCM Treatment Group
Neoadjuvant chemotherapy combined with immune drug therapy (primarily based on a combination of Karelizumab, a Platinum-based drug, and either Albumin-bound Paclitaxel or Paclitaxel) based on the use of Yishen Qutong Granules, 10g/dose, Tid treatment, synchronized with immunotherapy and chemotherapy
干预措施: Yishen Qutong Granules (Drug)
Chemoimmunotherapy TCM Simulant Group
Neoadjuvant chemotherapy combined with immune drug therapy (primarily based on a combination of Karelizumab, a Platinum-based drug, and either Albumin-bound Paclitaxel or Paclitaxel) based on the use of Yishen Qutong Simulant granules (1/10 Yishen Qutong Granules), 10g/dose, Tid treatment, used in tandem with immunotherapy, chemotherapy
干预措施: Yishen Qutong Simulant Granules (Drug)
结局指标
主要结局
clinical benefit rate (CBR)
时间窗: Assessed after completion of neoadjuvant therapy (2-4 cycles) and post-surgery, typically within 2-5 months after enrollment.
clinical benefit rate, CBR=(CR+PR+SD)
Symptom Score
时间窗: Assessed at the end of each treatment cycle (each cycle is 28 days), up to 5 cycles.
Assess the symptom scores of esophageal squamous cell carcinoma using a questionnaire. Esophageal Cancer Obstruction and Dysphagia Symptom Score: 0: No obstruction, does not affect eating at all 1. Very mild sensation of obstruction, does not affect eating 2. Mild obstruction, does not affect eating 3. Mild obstruction but occasionally increased sensation of obstruction, very mildly affects eating, does not affect intake of liquids 4. Mild obstruction, mildly affects eating 5. Mild obstruction but occasionally increased sensation of obstruction, affects eating, including liquids 6. Moderate obstruction, affects eating, including liquids 7. Moderate obstruction and occasionally increased sensation of obstruction, can only swallow liquids 8. Severe obstruction, can only consume very thin liquids 9. Severe obstruction, can only drink water 10. Complete obstruction
次要结局
- mPR resection rate(At the end of the surgery)
- R0 resection rate(At the end of the surgery)
- QLQ-C30 scale point(Assessed at the end of each treatment cycle (each cycle is 28 days), up to 5 cycles.)
- The NRS degree of pain caused by radiation esophagitis(Assessed at the end of each treatment cycle (each cycle is 28 days), up to 5 cycles.)
- Evaluation of Syndrome and Symptom Points of Traditional Chinese Medicine(Assessed at the end of each treatment cycle (each cycle is 28 days), up to 5 cycles.)
- Progression free survival (PFS)(After the completion of neoadjuvant concurrent therapy, patients will be followed up every 3 months for a total of 8 times (over 2 years), and their progression-free survival (PFS) will be recorded.)
- pathological complete response rate (pCR)(Assessed by surgical pathology within 10 days after surgery.)
- KPS score(Assessed at the end of each treatment cycle (each cycle is 28 days), up to 5 cycles.)
- Changes of the tongue(Assessed at the end of each treatment cycle (each cycle is 28 days), up to 5 cycles.)
- Changes of the pulse(Assessed at the end of each treatment cycle (each cycle is 28 days), up to 5 cycles.)