Phase II Randomized Window of Opportunity Trial of Chemoradiotherapy Alone Versus Combination With Metformin in Locally Advanced Cervical Cancer

LACC-MET

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.

2024-04-15

2025-08-01

2026-02-01

Not yet recruiting

Early phase I

51

Inclusion Criteria: 1. Ages 18-70 years old 2. Pathologically confirmed cervical squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma 3. FIGO stage IB2-IVA 4. Baseline CT or MRI indicating tumor necrosis (clinical hypoxia) 5. Hemoglobin ≥90g/L (blood transfusions allowed); no prior chemotherapy 6. ECOG performance status 0-2 7. No severe hematopoietic dysfunction, and no significant cardiac, pulmonary, hepatic, renal dysfunction, or immune deficiency 8. Able to undergo PET/CT imaging 9. Feasible for gynecological examination and cervical biopsy 10. Not pregnant or breastfeeding Exclusion Criteria: 1. 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. 2. Diagnosed diabetes mellitus or current use of metformin or any other antidiabetic medication. 3. 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%. 4. Serum transaminases exceeding 3 times the upper limit of normal, liver failure, alcohol poisoning. 5. History of allergic reactions to compounds chemically or biologically similar to metformin. 6. Concurrent hypoglycemia, such as insulinoma, autoimmune hypoglycemia, or functional hypoglycemia, or fasting blood glucose persistently less than 2.8 mmol/L before enrollment. 7. Malnutrition, BMI \<18.5. 8. Concurrent unhealed gastric ulcer, duodenal ulcer, ulcerative colitis, Crohn's disease, or recent episodes of severe abdominal pain, diarrhea, vomiting, etc. 9. Concurrent rectovaginal fistula, vesicovaginal fistula, uncontrolled vaginal bleeding, or those at risk of fistula. 10. Inability to undergo intracavitary radiotherapy as assessed by the investigator. 11. Human immunodeficiency virus (HIV) infection. 12. Severe underlying diseases that are untreatable. 13. History of other malignant tumors (excluding cured basal cell carcinoma of the skin) or previous pelvic radiotherapy. 14. Currently participating in other clinical trials or stopped participating in clinical trials less than 4 weeks ago. 15. Neurological or psychiatric abnormalities affecting cognitive function.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 51, 'type': 'ESTIMATED'}}

2024-04-08