Chemoradiotherapy With or Without Metformin in Locally Advanced Cervical Cancer

NCT06353061 | Recruiting Phase 2 DMC

• 1 other identifier: LACC-MET
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Cervical cancer

Outcome Measures

Primary Outcomes (1)

• The degree to which metformin improves the hypoxic index measured by CAIX PET

  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

  1week after randomization

Secondary Outcomes (4)

• Progression-free survival（PFS）

  2-year

• Changes in tumor volume during treatment

  Baseline，1month and 2 months.

• Hematologic and gastrointestinal toxicities assessed by CTCAE v5.0

  Up to 3 months after treatment.

• Quality of life assessed by QLQ-C30

  Up to 3 months after treatment

Study Arms (2)

The group treated with metformin in combination with synchronous chemoradiotherapy

EXPERIMENTAL

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.

Drug: Metformin; Radiation: Radiotherapy; Drug: Chemotherapy; Diagnostic Test: PET/CT

The group undergoing chemoradiotherapy alone.

ACTIVE COMPARATOR

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.

Radiation: Radiotherapy; Drug: Chemotherapy; Diagnostic Test: PET/CT

Interventions

Metformin 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.

The group treated with metformin in combination with synchronous chemoradiotherapy

Radiotherapy 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.

The group treated with metformin in combination with synchronous chemoradiotherapy; The group undergoing chemoradiotherapy alone.

Chemotherapy 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.

The group treated with metformin in combination with synchronous chemoradiotherapy; The group undergoing chemoradiotherapy alone.

PET/CT 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 treated with metformin in combination with synchronous chemoradiotherapy; The group undergoing chemoradiotherapy alone.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 \<18.5.
• 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.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, 310013, China

RECRUITING

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Hypoxia

Interventions

Metformin; Radiotherapy; Drug Therapy; Positron Emission Tomography Computed Tomography

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Therapeutics; Positron-Emission Tomography; Tomography, Emission-Computed; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Tomography, X-Ray Computed; Multimodal Imaging; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Radionuclide Imaging; Tomography; Diagnostic Techniques, Radioisotope

Central Study Contacts

kang ren, PhD

CONTACT

+86-18810679890; kangren2021@126.com

Xiaorong Hou, PhD

CONTACT

+86-13811963013; hxr_pumch@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2024
• First Posted: April 8, 2024
• Study Start: April 15, 2024
• Primary Completion: August 1, 2025
• Study Completion: February 1, 2026
• Last Updated: January 14, 2025

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)