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

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ClinicalTrials.gov Identifier: NCT03129776
Recruitment Status : Recruiting
First Posted : April 26, 2017
Last Update Posted : April 10, 2019
Sponsor:
Collaborator:
Ontario Institute for Cancer Research
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

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.

Condition or disease Intervention/treatment Phase
Uterine Cervical Neoplasms Drug: Hyperpolarized 13C-Pyruvate Drug: 18F-FDG Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: Up to ten participants with newly diagnosed FIGO stage IB-IVA cervical cancer that are to receive definitive radiation with or without concurrent cisplatin, are to be recruited for this prospective single institutional study. Participants will receive a hyperpolarized carbon 13 MR spectroscopy and PET scan in addition to the standard imaging that is required for staging. A tumour biopsy will be obtained at the time of the initial clinic visit.
Masking: None (Open Label)
Primary Purpose: Screening
Official Title: Hyperpolarized 13C MR Imaging of Lactate in Patients With Locally Advanced Cervical Cancer for Treatment With Definitive Chemoradiation Therapy
Actual Study Start Date : November 13, 2017
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. Time resolved, 3D 13C lactate images from subjects with cervical cancer. [ Time Frame: 1 year ]
    Feasibility of acquiring time resolved, 3D 13C lactate images from subjects with cervical cancer.


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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Only biological females with a cervix will be recruited.
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03129776


Contacts
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Contact: Julie Green, MSc 416.480.6100 ext 83655 julie.green@sunnybrook.ca
Contact: Charles Cunningham, PhD 416.480.5021 charles.cunningham@sunnybrook.ca

Locations
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Canada, Ontario
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Julie Green, MSc    416-480-6100 ext 83655    julie.green@sunnybrook.ca   
Principal Investigator: Charles Cunningham, PhD         
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Ontario Institute for Cancer Research

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Responsible Party: Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT03129776     History of Changes
Other Study ID Numbers: 355-2016
First Posted: April 26, 2017    Key Record Dates
Last Update Posted: April 10, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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

Additional relevant MeSH terms:
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Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Fluorodeoxyglucose F18
Radiopharmaceuticals
Molecular Mechanisms of Pharmacological Action