Tumor Hypoxia With HX4 PET in Several Diseases

Study Purpose

Regulation of tissue oxygen homeostasis is critical for cell function, proliferation and survival. Evidence for this continues to accumulate along with our understanding of the complex oxygen-sensing pathways present within cells. Several pathophysiological disorders are associated with a loss in oxygen homeostasis, including heart disease, stroke, and cancer. The microenvironment of tumors in particular is very oxygen heterogeneous, with hypoxic areas which may explain our difficulty treating cancer effectively. Prostate carcinomas are known to be hypoxic. Increasing levels of hypoxia within prostatic tissue is related to increasing clinical stage, patient age and a more aggressive prostate cancer. Several researches indicated that hypoxia might also play a role in esophageal cancer. In glial brain tumors, hypoxia is correlated with more rapid tumor recurrence and the hypoxic burden in newly diagnosed glioblastomas is linked to the biological aggressiveness. In brain metastases CA-IX expression (a marker for hypoxia) is correlated to the primary non-small cell lung carcinomas. Hypoxia enhances proliferation, angiogenesis, metastasis, chemoresistance and radioresistance of hepatocellular carcinoma. The hypoxic markers HIF-1α, VEGF, CA-IX and GLUT-1 were all over expressed in colorectal cancer and its liver metastases. Based on literature, hypoxia in tumors originating or disseminated to prostate, esophagus, brain and rectum cancer will be studied in this trial.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Histological/cytological confirmed carcinoma of de esophagus, rectum or prostate or radiological suspicion for Grade IV glioma (primary brain tumor) or brain metastases - WHO performance status 0 to 2.

- Adequate renal function (calculated creatinine clearance at least 60 ml/min).

- The patient is willing and capable to comply with study procedures - 18 years or older - Have given written informed consent before patient registration

Exclusion Criteria:

- Recent (< 3 months) myocardial infarction - Pregnant or breast feeding and willing to take adequate contraceptive measures during the study

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT02584400
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Maastricht Radiation Oncology
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Philippe Lambin, Prof. dr.
Principal Investigator Affiliation	Maastro Clinic, The Netherlands
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Netherlands
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Prostatic Neoplasms, Esophageal Neoplasms, Neoplasm Metastases, Brain, Rectal Neoplasms, Brain Neoplasm, Primary

Additional Details

Rationale: Non-invasive imaging of hypoxia with the aid of PET-scans could help to select the patients having a hypoxic tumor, who could be treated with specific anti-hypoxic treatments. The added value of additional anti-hypoxic treatments depends on the presence of hypoxia and adequate patient selection. Several 2-nitroimidazoles, labeled with Fluor-18 (18F) have already been used in patients to identify hypoxia. However, suboptimal image quality and unpredictable kinetics limit their use. In extensive pre-clinical models and clinical trials the combination of HX4 labeled with 18F showed to be a promising and non-toxic new probe to determine hypoxia. With this tracer the proportion of hypoxic tumors in several cancer types will be verified. Objective: Determine if tumor hypoxia can be accurately visualized with [18F]HX4 in solid lesions. Study design: Phase II, several solid tumors, single-centre, imaging, non-randomized, open label trial. Study population: Main patient characteristics are:

- Histological/cytological confirmed carcinoma of de esophagus, rectum or prostate or radiological suspicion for Grade IV glioma (primary brain tumor) or brain metastases.

- WHO performance status 0 to 2 - Adequate renal function (calculated creatinine clearance at least 60 ml/min).

- Capable of complying with study procedures Main intervention: In addition to standard clinical care patients receive two additional PET scans after injection with the hypoxia tracer [18F]HX4.

Main study parameters/endpoints:

- Visualization and quantification of tumor hypoxia with [18F] HX4 PET imaging - Exploring the potential relationship between [18F] HX4 uptake with local and locoregional tumor recurrence and survival - Correlation of hypoxia imaging with blood hypoxia markers - Correlation of hypoxia imaging with tumor tissue biomarkers - Evaluation of tumor hypoxia changes during treatment.

- Spatial correlation of [18F] HX4-PET with imaging pre-treatment (if present from routine clinical practice) - Spatial correlation of [18F] HX4-PET with imaging three months after treatment (if present from routine clinical practice) - Quantitative and qualitative correlation of [18F] HX4-PET obtained before treatment and two weeks into treatment Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The radiation burden due to [18F]HX4 is similar to that encountered in many routine nuclear medicine procedures e.g. [18F]FDG PET.

Administration of [18F]HX4 presents no known risks. In previous studies (healthy volunteers, phase I, phase II) no adverse effects were observed. There are no immediate potential benefits except the satisfaction to participate to improve of knowledge.

Contact a Trial Team

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International Sites

MAASTRO Clinic, Maastricht, Limburg, Netherlands

Status

Recruiting

Address

MAASTRO Clinic

Maastricht, Limburg, 6202 NA

Site Contact

Maaike Berbee, dr.

maaike.berbee@maastro.nl

+31884455666

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