Phase II Randomized Window of Opportunity Trial of Chemoradiotherapy Alone Versus Combination With Metformin in Locally Advanced Cervical Cancer
Overview
- Phase
- Phase 2
- Intervention
- Metformin
- Conditions
- Cervical Cancer
- Sponsor
- Peking Union Medical College Hospital
- Enrollment
- 51
- Locations
- 1
- Primary Endpoint
- The degree to which metformin improves the hypoxic index measured by CAIX PET
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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.
Arms & Interventions
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.
Intervention: Metformin
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.
Intervention: Radiotherapy
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.
Intervention: Chemotherapy
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.
Intervention: PET/CT
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.
Intervention: Radiotherapy
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.
Intervention: Chemotherapy
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.
Intervention: PET/CT
Outcomes
Primary Outcomes
The degree to which metformin improves the hypoxic index measured by CAIX PET
Time Frame: 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
Secondary Outcomes
- 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.)