Phase II Randomized Window of Opportunity Trial of Chemoradiotherapy Alone Versus Combination With Metformin in Locally Advanced Cervical Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- The degree to which metformin improves the hypoxic index measured by CAIX PET
研究概览
简要总结
This is a prospective, single-center, phase II, randomized, window-of-opportunity trial initiated by researchers. The research hypothesis is that metformin can improve the level of hypoxia in locally advanced cervical cancer and further improve progression-free survival. The study aims to compare the improvement of tumor hypoxia with synchronous chemoradiotherapy with or without metformin, using CA-IX PET/CT and radiation positioning spectral CT to evaluate tumor hypoxia, screening hypoxic patients for inclusion in the study, and comparing the effects of synchronous chemoradiotherapy with or without metformin on the degree of hypoxia and progression-free survival in the two groups of patients.
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
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Ages 18-70 years old
- •Pathologically confirmed cervical squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma
- •FIGO stage IB2-IVA
- •Baseline CT or MRI indicating tumor necrosis (clinical hypoxia)
- •Hemoglobin ≥90g/L (blood transfusions allowed); no prior chemotherapy
- •ECOG performance status 0-2
- •No severe hematopoietic dysfunction, and no significant cardiac, pulmonary, hepatic, renal dysfunction, or immune deficiency
- •Able to undergo PET/CT imaging
- •Feasible for gynecological examination and cervical biopsy
- •Not pregnant or breastfeeding
排除标准
- •Renal insufficiency with eGFR <45 ml‧min-1‧1.73 m-2, and acute conditions that may lead to renal impairment such as dehydration, severe infectious diseases, shock, etc.
- •Diagnosed diabetes mellitus or current use of metformin or any other antidiabetic medication.
- •Concurrent diseases that may lead to tissue hypoxia (especially acute or exacerbated chronic conditions), such as acute heart failure, pulmonary fibrosis, respiratory failure, recent myocardial infarction, or blood pressure monitoring showing less than 90/60 mmHg, SpO2 <90%.
- •Serum transaminases exceeding 3 times the upper limit of normal, liver failure, alcohol poisoning.
- •History of allergic reactions to compounds chemically or biologically similar to metformin.
- •Concurrent hypoglycemia, such as insulinoma, autoimmune hypoglycemia, or functional hypoglycemia, or fasting blood glucose persistently less than 2.8 mmol/L before enrollment.
- •Malnutrition, BMI <18.
- •Concurrent unhealed gastric ulcer, duodenal ulcer, ulcerative colitis, Crohn's disease, or recent episodes of severe abdominal pain, diarrhea, vomiting, etc.
- •Concurrent rectovaginal fistula, vesicovaginal fistula, uncontrolled vaginal bleeding, or those at risk of fistula.
- •Inability to undergo intracavitary radiotherapy as assessed by the investigator.
- •Human immunodeficiency virus (HIV) infection.
- •Severe underlying diseases that are untreatable.
- •History of other malignant tumors (excluding cured basal cell carcinoma of the skin) or previous pelvic radiotherapy.
- •Currently participating in other clinical trials or stopped participating in clinical trials less than 4 weeks ago.
- •Neurological or psychiatric abnormalities affecting cognitive function.
研究组 & 干预措施
The group treated with metformin in combination with synchronous chemoradiotherapy
After the group allocation is determined, patients in the experimental group will undergo CA-IX PET/CT scans. Subsequently, they will commence taking metformin at a dose of 850 mg per tablet, once daily, for three consecutive days. One week later, a second CA-IX PET/CT scan will be performed. Following this, synchronous chemoradiotherapy will be initiated, with patients taking metformin twice daily during the course of radiotherapy, at a dosage of one tablet per administration.
干预措施: Metformin (Drug)
The group treated with metformin in combination with synchronous chemoradiotherapy
After the group allocation is determined, patients in the experimental group will undergo CA-IX PET/CT scans. Subsequently, they will commence taking metformin at a dose of 850 mg per tablet, once daily, for three consecutive days. One week later, a second CA-IX PET/CT scan will be performed. Following this, synchronous chemoradiotherapy will be initiated, with patients taking metformin twice daily during the course of radiotherapy, at a dosage of one tablet per administration.
干预措施: Radiotherapy (Radiation)
The group treated with metformin in combination with synchronous chemoradiotherapy
After the group allocation is determined, patients in the experimental group will undergo CA-IX PET/CT scans. Subsequently, they will commence taking metformin at a dose of 850 mg per tablet, once daily, for three consecutive days. One week later, a second CA-IX PET/CT scan will be performed. Following this, synchronous chemoradiotherapy will be initiated, with patients taking metformin twice daily during the course of radiotherapy, at a dosage of one tablet per administration.
干预措施: Chemotherapy (Drug)
The group treated with metformin in combination with synchronous chemoradiotherapy
After the group allocation is determined, patients in the experimental group will undergo CA-IX PET/CT scans. Subsequently, they will commence taking metformin at a dose of 850 mg per tablet, once daily, for three consecutive days. One week later, a second CA-IX PET/CT scan will be performed. Following this, synchronous chemoradiotherapy will be initiated, with patients taking metformin twice daily during the course of radiotherapy, at a dosage of one tablet per administration.
干预措施: PET/CT (Diagnostic Test)
The group undergoing chemoradiotherapy alone.
Patients in the control group will undergo the first CA-IX PET/CT scan after the group allocation. One week later, they will undergo the second PET/CT scan. Subsequently, they will commence synchronous chemoradiotherapy.
干预措施: Radiotherapy (Radiation)
The group undergoing chemoradiotherapy alone.
Patients in the control group will undergo the first CA-IX PET/CT scan after the group allocation. One week later, they will undergo the second PET/CT scan. Subsequently, they will commence synchronous chemoradiotherapy.
干预措施: Chemotherapy (Drug)
The group undergoing chemoradiotherapy alone.
Patients in the control group will undergo the first CA-IX PET/CT scan after the group allocation. One week later, they will undergo the second PET/CT scan. Subsequently, they will commence synchronous chemoradiotherapy.
干预措施: PET/CT (Diagnostic Test)
结局指标
主要结局
The degree to which metformin improves the hypoxic index measured by CAIX PET
时间窗: 1week after randomization
Using the uptake value parameter of CA-IX in PET/CT, comparing the changes in uptake values between the two scans as an indicator of improvement in hypoxia level
次要结局
- Hematologic and gastrointestinal toxicities assessed by CTCAE v5.0(Up to 3 months after treatment.)
- Progression-free survival（PFS）(2-year)
- Quality of life assessed by QLQ-C30(Up to 3 months after treatment)
- Changes in tumor volume during treatment(Baseline，1month and 2 months.)