Hyperpolarized 13C MR Imaging of Lactate in Patients With Locally Advanced Cervical Cancer (LACC) Cervical Cancer

Hyperpolarized 13C MR Imaging of Lactate in Patients With Locally Advanced Cervical Cancer for Treatment With Definitive Chemoradiation Therapy

The purpose of this study is to image tumour lactate in study participants with locally advanced cervical cancer. Our hypothesis is that lactate content in cervical tumours, as measured by hyperpolarized 13C Magnetic Resonance (MR) imaging, will correlate with diffusion-weighted MRI and 18FDG-PET (fluorodeoxyglucose-positron emission tomography). Furthermore, lactate imaging will potentially provide additional and more specific information regarding the metabolic activity of cervical tumours, thereby identifying regions of radiation resistance and guiding radiation treatment and brachytherapy.

Study Overview

• Status: Terminated
• Conditions: Uterine Cervical Neoplasms
• Intervention / Treatment: Drug: Hyperpolarized 13C-Pyruvate; Drug: 18F-FDG

Detailed Description

Patients with locally advanced cervical cancer can be offered definitive treatment with radiation therapy with concurrent chemotherapy for curative treatment. Brachytherapy is an essential part of this treatment, used to deliver high central doses after external beam radiation. Three-dimensional image-guided brachytherapy (3DIGBT) is gradually becoming the standard of care in many centres across the world. The use of Magnetic Resonance Imaging (MRI) or Computerized Tomography (CT) for planning helps ensure adequate coverage of tumours, minimizing doses to organs at risk. However, standard imaging modalities used in 3DIGBT typically include T2 and T1 weighted MRI sequences or CT scans and visualizing of the disease can often be challenging. Furthermore, it can be difficult to differentiate between active cervical cancer and fibrosis, leading to treatment of larger volumes when there is uncertainty (Akila contouring study).

High tumour lactate concentration has been linked to poor clinical outcomes in patients with solid tumours, including cervical cancers treated with radiation therapy [1, 2]. Three-dimensional imaging of tumour lactate in patients with locally advanced cervical cancers may be useful in identifying regions of radiation resistance and guiding treatment with chemoradiation and brachytherapy. The objective of this study is to image patients with locally advanced cervical cancer using hyperpolarized 13C MR imaging to obtain a measure of lactate levels in cervical tumours. Lactate images and measurements will be correlated with diffusion-weighted MRI, 18FDG-PET imaging and bioluminescence microscopy (BLI).

Up to ten participants with cervical cancer that are to receive radical treatment with radiation and possible concurrent cisplatin will be recruited for this study from Sunnybrook Health Sciences Centre (Sunnybrook). A snap-frozen biopsy of the tumour will be taken at the first clinic visit. Prior to treatment, baseline diffusion weighted MRI images and 18FDG-PET scans will be obtained. Hyperpolarized 13C MR imaging will be performed through the injection of 13C pyruvate and measurements of tumour lactate levels. Lactate levels will be correlated with measurements from bioluminescence microscopy. The images from hyperpolarized 13C MR imaging will also be compared to diffusion-weighted MR and 18FDG-PET images.

The purpose of this study is to image tumour lactate in study participants with locally advanced cervical cancer. Our hypothesis is that lactate content in cervical tumours, as measured by hyperpolarized 13C Magnetic Resonance (MR) imaging, will correlate with diffusion-weighted MRI and 18FDG-PET. Furthermore, lactate imaging will potentially provide additional and more specific information regarding the metabolic activity of cervical tumours, thereby identifying regions of radiation resistance and guiding radiation treatment and brachytherapy.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma of the cervix, International Federation of Gynecology and Obstetrics (FIGO) stage IB-IVA
• Planned treatment with radical radiotherapy with or without concurrent cisplatin chemotherapy.
• Age ≥ 18 years.

Exclusion Criteria:

• Any anticancer treatment for their cervical cancer.
• Eastern Cooperative Oncology Group (ECOG) performance status > 2
• Other cervical cancer tumor histologies (e.g. small cell, serous)
• Contraindications to 18FDG PET-CT
• Inability to lie supine for 18FDG PET-CT
• Contraindication to radiotherapy (e.g. severe Crohn's disease)
• History of another invasive malignancy, except for non-melanoma skin cancer or tumors curatively treated with no evidence of disease for ≥ 5 years.
• Known pregnancy or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Hyperpolarized Pyruvate (13C) Injection; Participants will be injected with the study drug Hyperpolarized Pyruvate (13C) Injection at a dose of 0.43 ml/kg and will have their cervix imaged using MRI.	Drug: Hyperpolarized 13C-Pyruvate; The new imaging method being tested is called Metabolic MRI, which provides pictures of the metabolism occurring within cancer cells. It also involves injection of a contrast agent, Hyperpolarized Pyruvate (13C) Injection, into the arm vein. The participants will be injected with the study drug at a dose of 0.43 ml/kg and then receive a MRI scan.
Active Comparator: 18F-FDG; Participants will be injected with the study drug 18F-FDG at a dose of 5 MBq/kg to a a maximum of 500 MBq (megabecquerel) and will have their cervix imaged using PET-CT imaging.	Drug: 18F-FDG; 18F-FDG is a radiopharmaceutical used in medical imaging. The uptake of 18F-FDG by tissues is a marker for the tissue uptake of glucose, which is correlated with certain types of tissue metabolism, particularly in cancer cells. The participant will be injected with the study drug at a dose of 5 MBq/kg to a maximum of 500 MBq and then receive a PET scan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time resolved, 3D 13C lactate images from subjects with cervical cancer.	Feasibility of acquiring time resolved, 3D 13C lactate images from subjects with cervical cancer.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of MRI and 18FDG-PET images	Visual analysis and correlation between images obtained following Hyperpolarized Pyruvate (13C) Injection and 18FDG-PET imaging to identify cervical cancer.	1 Year

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Ontario Institute for Cancer Research

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2017
• Primary Completion (Actual): September 15, 2022
• Study Completion (Actual): September 15, 2022

Study Registration Dates

• First Submitted: April 17, 2017
• First Submitted That Met QC Criteria: April 21, 2017
• First Posted (Actual): April 26, 2017

Study Record Updates

• Last Update Posted (Actual): September 22, 2022
• Last Update Submitted That Met QC Criteria: September 20, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms
• Other Study ID Numbers: 355-2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes