Chemoradiotherapy With or Without Metformin in Locally Advanced Cervical Cancer

NCT ID: NCT06353061

Last Updated: 2025-01-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

51 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-15

Study Completion Date

2026-02-01

Brief Summary

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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.

Detailed Description

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Conditions

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Cervical Cancer Radiotherapy Metformin Hypoxia PET/CT

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Metformin

Intervention Type DRUG

Patients randomized to the metformin group will start taking metformin within 1 day after group allocation. They will take one tablet of metformin (850 mg) once daily for three consecutive days. Subsequently, they will take metformin orally twice daily throughout the entire external and internal irradiation period, with each administration consisting of one tablet.

Radiotherapy

Intervention Type RADIATION

The study requires all subjects to sequentially undergo external beam radiotherapy (EBRT) and intracavitary brachytherapy (BT). All radiotherapy must be completed within 7-8 weeks after treatment initiation. The total prescribed dose EQD2 for EBRT combined with BT should be ≥80 Gy; for subjects with squamous carcinoma with lesions ≤4 cm, the HR-CTV D90 should be ≥80 Gy; for subjects with adenocarcinoma or lesions \>4 cm, it is recommended that HR-CTV D90 should be ≥85 Gy. When the prescribed dose is limited by organs at risk (OAR), priority should be given to covering HR-CTV. The radiotherapy plan in this study is based on image guidance. Imaging scans can use MRI or CT, and the scanning area should extend at least 5 cm above and below the PTV.

Chemotherapy

Intervention Type DRUG

The dosage of cisplatin is 40 mg/m2, administered once weekly during radiotherapy for a duration of 5 weeks. Prior to and following cisplatin administration, 1-2 liters of fluid should be given for adequate hydration. Treatment should continue until disease progression or intolerable toxicity occurs.

PET/CT

Intervention Type DIAGNOSTIC_TEST

Using 68Ga-NY104 as a small molecule targeted imaging agent for CA-IX, two CA-IX PET/CT scans will be conducted in patients: one upon enrollment and another one week after randomization.

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.

Group Type ACTIVE_COMPARATOR

Radiotherapy

Intervention Type RADIATION

The study requires all subjects to sequentially undergo external beam radiotherapy (EBRT) and intracavitary brachytherapy (BT). All radiotherapy must be completed within 7-8 weeks after treatment initiation. The total prescribed dose EQD2 for EBRT combined with BT should be ≥80 Gy; for subjects with squamous carcinoma with lesions ≤4 cm, the HR-CTV D90 should be ≥80 Gy; for subjects with adenocarcinoma or lesions \>4 cm, it is recommended that HR-CTV D90 should be ≥85 Gy. When the prescribed dose is limited by organs at risk (OAR), priority should be given to covering HR-CTV. The radiotherapy plan in this study is based on image guidance. Imaging scans can use MRI or CT, and the scanning area should extend at least 5 cm above and below the PTV.

Chemotherapy

Intervention Type DRUG

The dosage of cisplatin is 40 mg/m2, administered once weekly during radiotherapy for a duration of 5 weeks. Prior to and following cisplatin administration, 1-2 liters of fluid should be given for adequate hydration. Treatment should continue until disease progression or intolerable toxicity occurs.

PET/CT

Intervention Type DIAGNOSTIC_TEST

Using 68Ga-NY104 as a small molecule targeted imaging agent for CA-IX, two CA-IX PET/CT scans will be conducted in patients: one upon enrollment and another one week after randomization.

Interventions

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Metformin

Patients randomized to the metformin group will start taking metformin within 1 day after group allocation. They will take one tablet of metformin (850 mg) once daily for three consecutive days. Subsequently, they will take metformin orally twice daily throughout the entire external and internal irradiation period, with each administration consisting of one tablet.

Intervention Type DRUG

Radiotherapy

The study requires all subjects to sequentially undergo external beam radiotherapy (EBRT) and intracavitary brachytherapy (BT). All radiotherapy must be completed within 7-8 weeks after treatment initiation. The total prescribed dose EQD2 for EBRT combined with BT should be ≥80 Gy; for subjects with squamous carcinoma with lesions ≤4 cm, the HR-CTV D90 should be ≥80 Gy; for subjects with adenocarcinoma or lesions \>4 cm, it is recommended that HR-CTV D90 should be ≥85 Gy. When the prescribed dose is limited by organs at risk (OAR), priority should be given to covering HR-CTV. The radiotherapy plan in this study is based on image guidance. Imaging scans can use MRI or CT, and the scanning area should extend at least 5 cm above and below the PTV.

Intervention Type RADIATION

Chemotherapy

The dosage of cisplatin is 40 mg/m2, administered once weekly during radiotherapy for a duration of 5 weeks. Prior to and following cisplatin administration, 1-2 liters of fluid should be given for adequate hydration. Treatment should continue until disease progression or intolerable toxicity occurs.

Intervention Type DRUG

PET/CT

Using 68Ga-NY104 as a small molecule targeted imaging agent for CA-IX, two CA-IX PET/CT scans will be conducted in patients: one upon enrollment and another one week after randomization.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Peking Union Medical College Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Peking Union Medical College Hospital

Beijing, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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kang ren, PhD

Role: CONTACT

+86-18810679890

Xiaorong Hou, PhD

Role: CONTACT

+86-13811963013

Facility Contacts

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xiaorong hou, Dr

Role: primary

+8618810679890

Other Identifiers

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LACC-MET

Identifier Type: -

Identifier Source: org_study_id

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