Chemoradiotherapy with or without metformin for advanced cervical cancer

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

This study is testing if adding metformin to standard treatment can help improve outcomes for patients with advanced cervical cancer by reducing tumor hypoxia during chemoradiotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 51 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Peking Union Medical College Hospital (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Beijing)
• Trial ID: NCT06353061 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effects of metformin on tumor hypoxia in patients with locally advanced cervical cancer undergoing chemoradiotherapy. It is a phase II, randomized, window-of-opportunity trial that aims to compare the progression-free survival and hypoxia levels in patients receiving chemoradiotherapy alone versus those receiving it alongside metformin. The study utilizes CA-IX PET/CT imaging to evaluate tumor hypoxia and screen eligible patients. The goal is to determine if metformin can enhance treatment outcomes by improving hypoxia levels.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-70 with pathologically confirmed locally advanced cervical cancer and clinical hypoxia.

Not a fit: Patients with renal insufficiency, diabetes, or concurrent diseases leading to tissue hypoxia may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved progression-free survival rates for patients with locally advanced cervical cancer.

How similar studies have performed: Other studies have explored the use of metformin in cancer treatment, showing promising results, but this specific approach is novel.

Eligibility criteria

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.

Where this trial is running

Beijing

• Peking Union Medical College Hospital — Beijing, China (Recruiting)

Study contacts

• Study coordinator: kang ren, PhD

Conditions Cervical Cancer; Radiotherapy; Metformin; Hypoxia; PET/CT; Cervical cancer