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Role of Hyperpolarized 13C-Pyruvate MR Spectroscopy in Patients With Intracranial Metastasis Treated With (SRS)

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ClinicalTrials.gov Identifier: NCT03324360
Recruitment Status : Recruiting
First Posted : October 27, 2017
Last Update Posted : March 29, 2021
Sponsor:
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

Tracking Information
First Submitted Date  ICMJE October 4, 2017
First Posted Date  ICMJE October 27, 2017
Last Update Posted Date March 29, 2021
Actual Study Start Date  ICMJE December 6, 2017
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 24, 2017)
Is an MRI image produced? Y/N? [ Time Frame: ~30-60 minutes of MRI time. ]
To demonstrate the first 13C-metabolic images of the human brain, alone with the required hardware and data acquisition methods.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Role of Hyperpolarized 13C-Pyruvate MR Spectroscopy in Patients With Intracranial Metastasis Treated With (SRS)
Official Title  ICMJE The Feasibility and Role of Hyperpolarized 13C-Pyruvate MR Spectroscopy in Monitoring Patients With Intracranial Metastasis Treated With Stereotactic Radiosurgery (SRS)
Brief Summary

Upwards of 40% of cancer patients will develop brain metastases during their illness, most of which become symptomatic. The burden of brain metastases impacts the quality and length of survival. Thus the management of brain metastases is a significant health care problem. Standard treatment options include stereotactic radiosurgery and/or whole brain radiation. There is a great interest in studying the association between the functional characteristics of tumors - such as tumour hypoxia and lactate accumulation - and clinical outcomes in order to guide management. These characteristics may predict future tumor behavior and stratify risk of therapy failure. Hyperpolarized 13C MR imaging is a novel functional imaging technique that uses 13C-labeled molecules, such as pyruvate, and MRS to image in vivo tissue metabolism.

There is significant clinical heterogeneity in patients with brain metastasis due to differences in underlying tumour biology. Biochemical differences in tumour metabolism have been shown to correlate with response to therapy. While the significance of tissue hypoxia for radiosensitivity has been established for years, the impact of lactate accumulation on radiosensitivity has only recently been recognized. Studies have shown that tissue lactate levels correlate with radioresistance in several human tumours. Hyperpolarized 13C pyruvate MRS has been shown in numerous pre-clinical studies and a recent clinical study to have great potential as a metabolic imaging tool. Our study seeks to establish the role of hyperpolarized 13C MRS in characterizing the metabolic features of intracranial metastasis. The results of this study will provide insight into intracranial metastatic disease signatures with MR spectroscopy and determine if there is added benefit for incorporation of this new technique into future clinical MRI protocols. If the technique can accurately differentiate between aggressive and indolent tumours based on MR spectroscopic patterns, hyperpolarized 13C MRS may have wide-ranging utility in the future. In the era of personalized medicine, the ability of imaging tests to predict response to therapy would open the door for individualized treatment options specific to each patient's disease biology.

Detailed Description

This is a pilot prospective, single-institution study in both control participants, control participants with mild cognitive impairment and Alzheimer's disease and participants with evidence of intracranial metastases who will be planned for brain radiation therapy. Control participant accrual will be done through advertisements. For control participants with mild cognitive impairment, Alzheimer's disease and intracranial metastatic disease screening and accrual will be completed by a member of the participant's Circle of Care. Clinical procedures will be completed at Sunnybrook Health Sciences Centre (SHSC) by the study's Qualified Investigator or medical designate. Eligible control participants must meet the study's inclusion and exclusion criteria and MRI eligibility. Intracranial metastatic participants must meet the study's inclusion and exclusion criteria, MRI eligibility will be undergoing radiation therapy (stereotactic radiotherapy).

The study will be divided into three parts:

Part I (Controls)

  • Population: up to 106 study participants, ≥18 years of age
  • Each participant in Groups A to G and J and K will undergo a single MRI sequence with a single hyperpolarized 13C pyruvate injection. Participants in group H and I will undergo MRI sequences with two consecutive injections of hyperpolarized 13C pyruvate. The scans are expected to be of approximately 60 to 75 minutes in length.

Group A: up to 6 participants ≥ 18 years of age. Group B: up to 10 male participants between the age of 18-39 Group C: up to 10 female participants between the age of 18-39 Group D: up to 10 male participants between the age of 40-59 Group E: up to 10 female participants between the age of 40-59 Group F: up to 10 male participants ≥ 60 years of age Group G: up to 10 female participants ≥ 60 years of age Group H: up to 10 male or female participants ≥ 18 years of age Group I: up to 10 male or female participants ≥ 18 years of age Group J: up to 10 male or female participants ≥ 60 years of age with Mild Cognitive Impairment Group K: up to 10 male or female participants ≥ 60 years of age with Alzheimer's disease

Part II

  • Population: up to 5 study participants from the Odette Cancer Centre, ≥18 years of age with demonstrated intracranial metastasis on imaging (CT or MRI), who have been referred to clinic for radiotherapy consideration.
  • Procedure: Each participant will undergo additional MRI sequences (hyperpolarized 13C pyruvate MRS) with an additional length of approximately 30-60 minutes that will be performed on the day of or in advance of the participant's routine radiation planning scan prior to radiation treatment. No extra visits to the hospital, beyond routine clinical care, are anticipated.

Part III

  • Population: up to 30 study participants from the Odette Cancer Centre, ≥18 years of age with demonstrated intracranial metastasis on imaging (CT or MRI), who have been referred to clinic for radiotherapy consideration.
  • Procedure: Each participant will undergo additional MRI sequences (hyperpolarized 13C pyruvate MRS) with an additional length of approximately 30-60 minutes that will be performed on the day of or in advance of the participant's routine radiation planning scan prior to radiation treatment In addition, each participant will undergo one non-routine MRI scan with a length of approximately 60-90 minutes at a time point of 1-5 days following radiation treatment.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Brain Metastases
Intervention  ICMJE Drug: Hyperpolarized 13C-Pyruvate
MRI with Hyperpolarized 13C-Pyruvate Injection
Study Arms  ICMJE
  • Experimental: Control Participants Part I
    A MRI with injection of hyperpolarized 13C pyruvate.
    Intervention: Drug: Hyperpolarized 13C-Pyruvate
  • Experimental: Intracranial Metastasis Part II
    MRI with injection of hyperpolarized 13C pyruvate prior to radiation treatment.
    Intervention: Drug: Hyperpolarized 13C-Pyruvate
  • Experimental: Intracranial Metastasis Part III
    MRI with injection of hyperpolarized 13C pyruvate prior to radiation treatment. MRI with injection of hyperpolarized 13C pyruvate1-5 days following radiation treatment.
    Intervention: Drug: Hyperpolarized 13C-Pyruvate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 14, 2020)
156
Original Estimated Enrollment  ICMJE
 (submitted: October 24, 2017)
41
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Part I (Controls) Group A

  • Participants of all ethnic groups/race categories (≥18yrs old)
  • Informed consent Group B
  • Male participants of all ethnic groups/race categories (between the age of 18-39)
  • Informed consent Group C
  • Female participants of all ethnic groups/race categories (between the age of 18-39)
  • Informed consent Group D
  • Male participants of all ethnic groups/race categories (between the age of 40-59)
  • Informed consent Group E
  • Female participants of all ethnic groups/race categories (between the age of 40-59)
  • Informed consent Group F
  • Male participants of all ethnic groups/race categories (≥60 yrs old)
  • Informed consent Group G
  • Female participants of all ethnic groups/race categories (≥60 yrs old)
  • Informed consent Group H and I
  • Male or female participants of all ethnic groups/race categories (≥18 yrs old)
  • Informed consent Group J
  • Male or female participants of all ethnic groups/race categories (≥60 yrs old)
  • Informed consent
  • Diagnosed with mild cognitive impairment Group K
  • Male or female participants of all ethnic groups/race categories (≥60 yrs old)
  • Informed consent
  • Diagnosed with mild Alzheimer's disease

Part II & III

  • Adult participants of all ethnic groups/race categories (age ≥18 yrs old)
  • Radiographic diagnosis of brain metastases and pathological confirmation of a solid cancer primary
  • At least 1 intracranial metastasis ≥1 cm in size
  • Metastatic brain tumour amenable to Stereotactic radiosurgery or radiotherapy
  • Participants on stable dexamethasone dose at the time of baseline MRI and 1-5 days post-SRS MRI
  • Estimated survival more than 6 months
  • Informed consent

Exclusion Criteria:

  • Prior brain radiotherapy for the specific index or lesion to be imaged in the study
  • For groups B to I only: Montreal Cognitive Assessment (MoCA) score <26
  • The participant will also be asked to complete the standard MRI safety screening questionnaire, prior to their research scan and participation in the study.
  • Contraindications to MRI including:
  • Participants weighing >136 kg (weight limit for the scanner tables)
  • Participants with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable electronic devices not compatible with MRI.
  • Pregnant
  • Claustrophobia to the extent that the participant cannot stay in the MRI for 45-60 minutes
  • Known adverse reactions to the contrast agent Gd-DTPA
  • Inability to lie still for 45-60 minutes
  • Participants with a high risk factor for nephrogenic systemic fibrosis (NFS).
  • Participant declines the procedure or further procedures;
  • Participant is not well enough to undergo MRI scanning;
  • Participant is unable to complete the MRI procedure for any reason or is non-compliant with MRI requirements.
  • For groups J and K, a <1 lacunar infarct or any cortical subcortical infarct or moderate to severe white matter disease
  • For groups J and K, any other structural brain lesion that could affect cognition
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Julie Green, MSc 416.480.6100 ext 83655 julie.green@sunnybrook.ca
Contact: Nadia Bragagnolo 416.480.6100 ext 83655 nadia.bragagnolo@sri.utoronto.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03324360
Other Study ID Numbers  ICMJE 333-2014
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sunnybrook Health Sciences Centre
Study Sponsor  ICMJE Sunnybrook Health Sciences Centre
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Charles Cunningham, PhD Sunnybrook Research Institute
PRS Account Sunnybrook Health Sciences Centre
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP