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

NCT ID: NCT03129776

Last Updated: 2022-09-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-13
• Study Completion Date: 2022-09-15

Brief Summary

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.

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.

Conditions

Uterine Cervical Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Hyperpolarized 13C-Pyruvate

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

18F-FDG

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Ontario Institute for Cancer Research

OTHER

Sponsor Role: collaborator

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

355-2016

Identifier Type: -

Identifier Source: org_study_id