Hyperpolarized 13C Pyruvate MRI for Early Immune Evaluation in Cervical Cancer Patients At Baseline and CCRT Therapy

NCT ID: NCT04951921

Last Updated: 2025-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-15
• Study Completion Date: 2024-07-31

Brief Summary

In this single armed, single-center, case-controlled study, the investigators will conduct a prospective trial and integrate the most advanced imaging technology to medical practice, attempting to solve the problem detected by radiomics approach. The investigators plan a 3-year project with non-randomized, single group assignment observational study design. Thirty participants with diagnosed LACC that are to receive CCRT are to be recruited for this prospective single institutional study from Chang Gung Memorial Hospital at Linkou (CGMH). Standard-of-care MRI/CT that is required for staging will be the first line screening method. A tumor biopsy and routine blood test will be obtained at the time of the initial clinic visit. Participants eligible for this study will receive two investigative exams-MRF, CEST, DNP-MRI MRI and Metabolomics, at baseline and the 2-week during CCRT.

The new imaging methods being tested are MRF and CEST without contrast enhancement, and DNP-MRI which provides quantitative measurement of the metabolism occurring within cancer cells. It also involves injection of a contrast agent-Hyperpolarized pyruvate (13C) Injection. The participants will be injected with the study drug at a dose of 0.43 ml/kg and then receive MRI scan.

Detailed Description

Primary objective

1. Bridging the Gap between Imaging and Biology. DNP is the only technology that can measure real-time flux of pyruvate to lactate conversion and mitochondria metabolism. DNP-MRI will combine the strength of MRI (anatomy, tissue contrast via MRF, CEST and DWI) and DNP (biochemistry measurement), and the blood/urine metabolomics approach, to noninvasively bring more insightful information for clinical application.

2. Precision Medicine for Precision Response Prediction. Although AI or deep learning can identify high-risk patient for particularly treatment (CCRT in this project), the predictive model is based on prior database rather than this particular patient. The investigators urgently need a non-invasive precise measurement to monitor the response in a real-world situation, to reduce the treatment uncertainty, to select the most cost-effective treatment. This is of paramount importance for the more advanced treatment i.e. target therapy, immunotherapy etc. The investigators did not intend to change the standard-of-care but the information provided by this study will help to investigate the fundamental mechanisms hence providing hopes for alternative treatments.

3. Infrastructures for MR Fingerprinting and Dynamic Nuclear Polarization (DNP)-MRI Research for Taiwanese researchers. The investigators are very grateful to be able to install the first DNP system dedicated to human research in Asia and would like to introduce this novel technology to Taiwan. Currently, human DNP study has only been conducted in the USA (UCSF, MD Anderson Cancer Center and Memorial Sloan-Kettering Cancer Center) and the UK (University College of London, Oxford and Cambridge) and Canada (Toronto University). Based on our preliminary efforts of tracer preparation, multi-nuclei scanning equipment and dedicated pulse sequences, the investigators aim to build infrastructures for MR Fingerprinting and DNP-MRI Research for Taiwanese research groups.

Secondary objective

1. Translate technical advancements to clinically applicable tools

2. Converge integrated information to construct the prediction model

3. Establish the delta radiomics prediction model with biological meaningfulness

Conditions

Cervical Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Hyperpolarized 13C pyruvate DNP-MRI scan

Patients receive hyperpolarized 13C pyruvate through IV injection less than 1-2 minute then undergo MRI over 3-5 minutes at baseline and 2 weeks after CCRT treatment. Total 2 times of MRI scan.

Group Type: EXPERIMENTAL

Hyperpolarized 13C Pyruvate

Intervention Type: DRUG

Procedure: Magnetic Resonance Imaging Undergo 1H-MRI of DWI/MRF/CEST for tumor cite following by 13C DNP-MRI for spleen for 3-5 minutes after hyperpolarized 13C pyruvate injection

Interventions

Hyperpolarized 13C Pyruvate

Procedure: Magnetic Resonance Imaging Undergo 1H-MRI of DWI/MRF/CEST for tumor cite following by 13C DNP-MRI for spleen for 3-5 minutes after hyperpolarized 13C pyruvate injection

Intervention Type: DRUG

Other Intervention Names

Hyperpolarized Carbon C 13 Pyruvate; Hyperpolarized Pyruvate (13C)

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed carcinoma of the uterine cervix.

2. Age ≥ 20 years.

3. Clinical International Federation of Gynecology and Obstetrics (FIGO) stage IB2-IV.

4. Tumor diameter ≥ 4 cm, verified by MRI or CT.

5. Scheduled curative-intent non-surgical treatment.

Exclusion Criteria

1. Contraindication to MRI study (e.g. claustrophobia, cardiac pacemaker, metal implants in pelvis).

2. Inadequate marrow, liver and renal functions.

3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

4. Pregnant or breast-feeding women.

• Minimum Eligible Age: 20 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Science and Technology, Taiwan

OTHER_GOV

Sponsor Role: collaborator

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Gigin Lin

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gigin Lin, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Chang Gung Memorial Hospital

Locations

Chang Gung Memorial Hospital

Taoyuan, Guishan District, Taiwan

Countries

Taiwan

References

Lin G, Hsieh CY, Lai YC, Wang CC, Lin Y, Lu KY, Chai WY, Chen AP, Yen TC, Ng SH, Lai CH. Hyperpolarized [1-13C]-pyruvate MRS evaluates immune potential and predicts response to radiotherapy in cervical cancer. Eur Radiol Exp. 2024 Apr 10;8(1):46. doi: 10.1186/s41747-024-00445-1.

Reference Type: DERIVED

PMID: 38594558 (View on PubMed)

Other Identifiers

201702080A0

Identifier Type: -

Identifier Source: org_study_id