Clinical trial NCT02584400: Tumor Hypoxia With HX4 PET in Several Diseases
Official title: Non-invasive Imaging of Tumor Hypoxia With [18F]HX4 Positron-Emission-Tomography (PET): A Phase II Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Prostatic Neoplasms
Esophageal Neoplasms
Neoplasm Metastases, Brain
Rectal Neoplasms
Brain Neoplasm, Primary
Keywords: prostatic tumors
[18F]HX4 Pet imaging
hypoxia
phase II trial
esophageal tumors
rectal tumors
brain metastases
primary brain tumors
Lead sponsor: Maastricht Radiation Oncology
Sponsor class: OTHER
First posted: 2015-10-22
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: 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.

Eligibility 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

Primary outcomes:
measure: Visualization of tumor hypoxia with [18F] HX4 PET imaging, valuated by the measurement of a tumor-to-background (T/B) ratio on the [18F]HX4 PET/CT
timeFrame: 4 years
measure: Quantification of tumor hypoxia with [18F] HX4 PET imaging, evaluated by the measurement of a tumor-to-background (T/B) ratio on the [18F]HX4 PET/CT
timeFrame: 4 years
Secondary outcomes:
measure: Time between [18F] HX4 uptake with local and locoregional tumor recurrence and survival
timeFrame: 4 years
measure: Correlation of hypoxia imaging with blood hypoxia markers will be measured by the Pearson or Spearman correlation coefficient
timeFrame: 4 years
measure: Correlation of hypoxia imaging with tumor tissue biomarkers will be measured by the Pearson or Spearman correlation coefficient
timeFrame: 4 years
measure: Evaluation of tumor hypoxia changes during treatment by comparison of the PET uptake values in the tumor, measured before and during treatment
timeFrame: 4 years
measure: Spatial correlation of [18F] HX4-PET with imaging pre-treatment using a correlation coefficient
timeFrame: 4 years
measure: Spatial correlation of [18F] HX4-PET with imaging three months after treatment using a correlation coefficient
timeFrame: 3 months
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: MAASTRO Clinic
state: Limburg
Study officials:
affiliation: Maastro Clinic, The Netherlands
name: Philippe Lambin, Prof. dr.
role: PRINCIPAL_INVESTIGATOR
References: