Assessment of Primary and Metastatic Brain Tumor Hypoxia With Fluoromisonidazole, FDG and Water

NCT ID: NCT01246869

Last Updated: 2024-10-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-27
• Study Completion Date: 2014-05-03

Brief Summary

Purpose of Study This exploratory clinical study will investigate FMISO (fluoromisonidazole) in patients with (1) newly diagnosed primary malignant brain tumors (WHO [World Health Organization] Grade III or IV glial-based tumors) who have not had a complete surgical resection and by contrast MRI (Magnetic resonance imaging) have residual tumor > 1.0 cm in diameter and will be receiving radiotherapy or (2) newly diagnosed brain metastasis (> 1.0 cm in diameter who will be receiving radiotherapy. The ability to accurately assess tumor hypoxia and accurately determine the amount/degree of tumor hypoxia could potentially change patient management once validated as tumor hypoxia is known to be associated with a poor prognosis [Eyler 2008].

Detailed Description

Malignant Brain Tumors (Primary and Metastatic) Despite significant advances in the understanding of brain tumor biology and genetics as well as improvements in surgical techniques, radiotherapy administration, and chemotherapy methods, many brain tumors remain incurable. Many brain tumors are highly infiltrative neoplasms, and are therefore unlikely to be cured by local treatments such as surgery, focal radiotherapy, radiosurgery or brachytherapy.

Rationale and Goals of Study The preliminary efficacy of the radiopharmaceutical, 1H-1-(3-[18F]-fluoro-2-hydroxy-propyl)-2-nitro-imidazole [18F]-fluoromisonidazole, [18F]FMISO, FMISO (fluoromisonidazole), a radiopharmaceutical that directly assess tumor hypoxia using Positron Emission Tomography(PET) will be assessed.

This preliminary/exploratory clinical study will investigate [F-18]FMISO in 30 evaluable patients with newly diagnosed primary brain tumor or brain metastasis. We expect that up to 35 -40 total patients may be enrolled in this study. This will assure that 30 evaluable patients (patients who have complete imaging results and blood metabolism data available for data analysis). In certain patients the blood metabolism data is not acceptable for final analysis typically due to difficulty in drawing it rapidly enough due to the vein collapsing during the rapid sampling required.

When possible we will also correlate FMISO uptake with the typical in-vitro test used to assess proliferation, Ki-67 (protein) and other experimental assessments of hypoxia. This correlation will be made whenever possible in those patients where tumor tissue is obtained as part of standard care.

OBJECTIVES:

Primary Objective of Study - Synopsis The primary objective of this study is to determine the association of FMISO PET (positron emission tomography) uptake (hypoxic volume (HV)), highest tumor:blood ratio [T/Bmax]), FDG ([18F]-2 fluoro-2-deoxy-d-glucose) uptake, and tumor blood flow/perfusion determined with water (H2O) and MRI and correlate these variables with overall survival (OS) and time to progression (TTP) in participants with newly diagnosed primary brain tumors or brain metastases.

The Hypotheses to be Tested

Three exploratory hypotheses will be studied. These include:

1. The first hypothesis to be tested is that increased FMISO PET uptake (hypoxic volume [HV], highest tumor:blood ratio [T/Bmax]) is correlated with a shorter overall survival and a shorter time to progression. An exploratory evaluation assessing combinations of PET imaging variables such as hypoxic volume [HV], highest tumor:blood ratio [T/Bmax], FDG-standardized uptake value (SUV), FDG quantitative parameters and blood flow as well as magnetic resonance (MR) perfusion and blood volume will be assessed to see if they correlate with survival and time to progression.

2. A second hypothesis to be tested is that FMISO is safe and non toxic in the dose administered in this study in patients with primary and metastatic brain tumors. This will be assessed in the first 10 patients enrolled in the study. Even though there have been numerous published studies using FMISO in humans in several different tumor types little human safety data has been published. Laboratory tests (except urinalysis) will be repeated at approximately 24 hours in the first 10 and compared to the screening values.

3. A third exploratory hypothesis to be tested is that FMISO uptake (hypoxic volume [HV], highest tumor:blood ratio [T/Bmax]) will correlate with increased FDG uptake and possibly with reduced blood flow/perfusion as determined with H215O PET imaging and MRI

Conditions

Brain Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

All Participants

All enrolled participants will complete three imaging sessions on separate days, beginning with a research MRI, then a PET scan with FDG and \[15O\]water, and a PET scan with FMISO. The two PET scans will be in any order on different days within one week of each other, and preferably on consecutive days. The research MRI will be within 14 days of the first PET scan.

Group Type: EXPERIMENTAL

[18F]fluoro-2-deoxy-D-glucose (FDG)

Intervention Type: DRUG

Brain scan with imaging tracer used for measuring glucose metabolism in the assessment, diagnosis, and staging of patients with cancer

1H-1-(3-[18F]-fluoro-2-hydroxy-propyl)-2-nitro-imidazole [18F]-fluoromisonidazole

Intervention Type: DRUG

Brain scan with radiopharmaceutical imaging tracer that directly assesses tumor hypoxia

[15O]water

Intervention Type: DRUG

Brain scan with imaging tracer used for measuring tumor blood flow/perfusion

Magnetic Resonance Imaging

Intervention Type: DIAGNOSTIC_TEST

Brain scan to assess tumor size and tumor blood flow/perfusion

Interventions

[18F]fluoro-2-deoxy-D-glucose (FDG)

Brain scan with imaging tracer used for measuring glucose metabolism in the assessment, diagnosis, and staging of patients with cancer

Intervention Type: DRUG

1H-1-(3-[18F]-fluoro-2-hydroxy-propyl)-2-nitro-imidazole [18F]-fluoromisonidazole

Brain scan with radiopharmaceutical imaging tracer that directly assesses tumor hypoxia

Intervention Type: DRUG

[15O]water

Brain scan with imaging tracer used for measuring tumor blood flow/perfusion

Intervention Type: DRUG

Magnetic Resonance Imaging

Brain scan to assess tumor size and tumor blood flow/perfusion

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

FDG; [18F]FDG; FDG-PET/CT; [18F]FMISO; FMISO; FMISO-PET/CT; H2[15O]; H2[15O]-PET-CT; MRI

Eligibility Criteria

Inclusion Criteria

1. Adult patients. The patient must have a newly diagnosed primary malignant brain tumors (WHO Grade III or IV glial-based tumors) and not have had a complete surgical resection and by contrast MRI (obtained within 14 days prior to the FMISO study)

2. Patients must be 18 years or older for inclusion in this research study.

3. Patients must document their willingness to be followed until death or time of progression.

4. All patients must sign a written informed consent and HIPAA authorization in accordance with institutional guidelines.

5. Female patients who are not postmenopausal or surgically sterile will undergo a serum pregnancy test prior to the research PET scans.

6. Pre-treatment laboratory tests for patients receiving [18F]FMISO must be performed within 21 days prior to study entry.

Exclusion Criteria

1. Patients with known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals.

2. Patients who are pregnant or lactating or who suspect they might be pregnant.

3. Adult patients who require monitored anesthesia for PET scanning.

4. Patients who are too claustrophobic to undergo MRI or PET imaging

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

Sponsors

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Yap, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Countries

United States

Other Identifiers

HCI44704

Identifier Type: -

Identifier Source: org_study_id