Image-Based, In-Vivo Assessment of Tumor Hypoxia to Guide Hypoxia-Driven Adaptive Radiation Therapy

Non-invasive, Image-Based, In-Vivo Assessment of Tumor Hypoxia to Guide Hypoxia-Driven Adaptive Radiation Therapy

This study will apply novel MRI approaches with established sensitivity to tissue oxygen consumption and perfusion to predict hypoxia-associated radiation resistance, manifested as tumor recurrence and progression post-treatment.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma; Brain Metastases
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging (MRI); Procedure: Positron Emission Tomography (PET); Drug: 18F-fluoromisonidazole

Detailed Description

Primary Objective:

- To validate non-invasive, MRI-based markers of tumor hypoxia in patients with brain metastases or head and neck cancer with and without evidence of tumor hypoxia identified by 18F-FMISO-PET-CT.

Secondary Objectives:

• To assess treatment-related changes in tumor and peritumoral tissue oxygen consumption and perfusion via non-invasive MRI.
• To evaluate the effect of pre-treatment and post-treatment (3 months) tumor hypoxia on tumor recurrence, progression, and radiation necrosis in patients with central nervous system metastases treated with standard of care stereotactic radiosurgery.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Vanderbilt-Ingram Services for Timely Access; Phone Number: 800-811-8480; Email: cip@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Vanderbilt University/Ingram Cancer Center
      • Contact: Vanderbilt-Ingram Service Services for Timely Access; Phone Number: 800-811-8480; Email: cip@vumc.org
      • Principal Investigator: Jill De Vis, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed head and neck squamous cell carcinoma or a clinical diagnosis of CNS-excluded nervous system neoplasm and disorder (brain metastases)
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions, minimum size 7mm) with CT scan, MRI, or calipers by clinical exam
• ECOG performance status </=1 Karnofsky >/=70%
• Life expectancy of greater than 6 months
• The effects of 18F-FMISO on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and up until the day after 18F-FMISO administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception on the days of 18F-FMISO administration
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 18F-FMISO
• 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
• Brain metastases >3.0 cm
• Dural-based metastases concerning for leptomeningeal disease
• Hemorrhage within the lesion of interest
• Patients presenting for radiation after surgical resection of brain metastasis/metastases or primary head and neck cancer (adjuvant radiotherapy)
• Prior or current known history of disease involving the brain other than brain metastases and including but not limited to; cerebrovascular disease (i.e., stroke or large vessel disease), brain hemorrhage (i.e., subarachnoid hemorrhage or intraparenchymal hemorrhage), Alzheimer's disease or dementia, Parkinson's disease, Multiple Sclerosis or schizophrenia
• Prior overlapping radiation fields
• Not suitable to undergo MRI because of; severe claustrophobia, presence of metallic objects or implanted medical devices in body (i.e., cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the imaging site, or steel implants)
• Presence of any other co-existing condition which, in the judgment of the investigator, might increase the risk to the subject
• Presence of serious systemic illness, including uncontrolled intercurrent infection or psychiatric/social situations which may limit compliance with study requirements
• Not suitable to undergo MRI, including weight greater than 350lbs (common weight limit for the MRI table)
• Prisoners, children <18 years of age
• Prior overlapping radiation fields
• Not suitable to undergo MRI because of; severe claustrophobia, presence of metallic objects or implanted medical devices in body (i.e., cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the imaging site, or steel implants)
• Presence of any other co-existing condition which, in the judgment of the investigator, might increase the risk to the subject
• Presence of serious systemic illness, including uncontrolled intercurrent infection or psychiatric/social situations which may limit compliance with study requirements
• Not suitable to undergo MRI, including weight greater than 350lbs (common weight limit for the MRI table)
• Prisoners, children <18 years of age
• The effects of 18F-FMISO on the developing infant are unknown. For this reason, nursing women will be excluded from the trial

Pregnant patients which will be identified as follows;

• Patients over the age of 60 do not require a pregnancy test per institutional guidelines. We anticipate this to be most of our patient population due to the age distribution of cancer patients.
• Patients under the age of 60 will be offered a point of care pregnancy test when seen in consult at the department of Radiation Oncology.
• Patients refusing pregnancy testing can sign a waiver stating that they refuse pregnancy testing but that they are not known to be pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Locally Advanced Squamous Cell Carcinoma of the Head and Neck; Participants will undergo magnetic resonance imaging (MRI) scans and positron emission tomography (PET) scans and administered the imaging agent 18F-fluoromisonidazole.	Procedure: Magnetic Resonance Imaging (MRI); Participants will undergo Magnetic Resonance Imaging; Procedure: Positron Emission Tomography (PET); Participants will undergo Positron Emission Tomography; Drug: 18F-fluoromisonidazole; Given by IV
Experimental: Brain metastases; Participants will undergo magnetic resonance imaging (MRI) scans and positron emission tomography (PET) scans and administered the imaging agent 18F-fluoromisonidazole.	Procedure: Magnetic Resonance Imaging (MRI); Participants will undergo Magnetic Resonance Imaging; Procedure: Positron Emission Tomography (PET); Participants will undergo Positron Emission Tomography; Drug: 18F-fluoromisonidazole; Given by IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validate non-invasive, MRI-based markers of tumor hypoxia in patients with brain metastases or head and neck cancer with and without evidence of tumor hypoxia identified by 18F-FMISO-PET-CT	MRI assessed oxygen extraction fraction (OEF, %)	1.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess treatment-related changes in tumor and peritumoral tissue oxygen consumption and perfusion via non-invasive MRI	MRI assessed oxygen extraction fraction (OEF, %)	4 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the effect of pre-treatment and post-treatment tumor hypoxia on outcome	Tumor recurrence	4 years
Evaluate the effect of pre-treatment and post-treatment tumor hypoxia on outcome	Radiation necrosis	4 years

Collaborators and Investigators

• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Jill De Vis, MD, PhD, Vanderbilt University/Ingram Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2023
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): May 31, 2029

Study Registration Dates

• First Submitted: July 13, 2023
• First Submitted That Met QC Criteria: August 10, 2023
• First Posted (Actual): August 18, 2023

Study Record Updates

• Last Update Posted (Actual): August 18, 2023
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Signs and Symptoms, Respiratory; Central Nervous System Neoplasms; Nervous System Neoplasms; Carcinoma, Squamous Cell; Brain Neoplasms; Squamous Cell Carcinoma of Head and Neck; Hypoxia
• Other Study ID Numbers: VICC-EDMDT23195

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No