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Tumor Hypoxia With HX4 PET in Several Diseases (HX4 SD)

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ClinicalTrials.gov Identifier: NCT02584400
Recruitment Status : Terminated (patients did not want to participate)
First Posted : October 22, 2015
Last Update Posted : March 8, 2019
Sponsor:
Information provided by (Responsible Party):
Maastricht Radiation Oncology

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.

Condition or disease Intervention/treatment Phase
Prostatic Neoplasms Esophageal Neoplasms Neoplasm Metastases, Brain Rectal Neoplasms Brain Neoplasm, Primary Drug: Injection with the hypoxia tracer [18F]HX4, Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Non-invasive Imaging of Tumor Hypoxia With [18F]HX4 Positron-Emission-Tomography (PET): A Phase II Trial
Study Start Date : May 2016
Actual Primary Completion Date : May 2017
Actual Study Completion Date : May 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: [18F]HX4 PET imaging
Injection with the hypoxia tracer [18F]HX4 and PET imaging at baseline for esophageal, rectal, prostate cancer, primary brain tumor (grade IV glioma) and brain metastases and after 2 weeks of radiotherapy for esophageal, rectal and brain metastases
Drug: Injection with the hypoxia tracer [18F]HX4,
The [18F]HX4 PET scan will be performed, by administrating 444 MBq (12 mCi) [18F]HX4 via a bolus IV injection.
Other Name: [18F]HX4 is 3-[18F]fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)propan-1-ol




Primary Outcome Measures :
  1. 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 [ Time Frame: 4 years ]
    Visualization of tumor hypoxia with [18F] HX4 PET imaging

  2. 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 [ Time Frame: 4 years ]
    Quantification of tumor hypoxia with [18F] HX4 PET imaging


Secondary Outcome Measures :
  1. Time between [18F] HX4 uptake with local and locoregional tumor recurrence and survival [ Time Frame: 4 years ]
    Exploring the potential relationship of [18F] HX4 uptake with local and locoregional tumor recurrence and survival

  2. Correlation of hypoxia imaging with blood hypoxia markers will be measured by the Pearson or Spearman correlation coefficient [ Time Frame: 4 years ]
    Correlation of hypoxia imaging with blood hypoxia markers

  3. Correlation of hypoxia imaging with tumor tissue biomarkers will be measured by the Pearson or Spearman correlation coefficient [ Time Frame: 4 years ]
    Correlation of hypoxia imaging with tumor tissue biomarkers

  4. Evaluation of tumor hypoxia changes during treatment by comparison of the PET uptake values in the tumor, measured before and during treatment [ Time Frame: 4 years ]
    Evaluation of tumor hypoxia changes during treatment

  5. Spatial correlation of [18F] HX4-PET with imaging pre-treatment using a correlation coefficient [ Time Frame: 4 years ]
    Spatial correlation of [18F] HX4-PET with imaging pre-treatment (if present from routine clinical practice); performed by a rigid registration of the scans and a voxel wise comparison of the uptake within the tumor

  6. Spatial correlation of [18F] HX4-PET with imaging three months after treatment using a correlation coefficient [ Time Frame: 3 months ]
    Spatial correlation of [18F] HX4-PET with imaging three months after treatment (if present from routine clinical practice), performed by a rigid registration of the scans and a voxel wise comparison of the uptake within the tumor



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02584400


Locations
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Netherlands
MAASTRO Clinic
Maastricht, Limburg, Netherlands, 6202 NA
Sponsors and Collaborators
Maastricht Radiation Oncology
Investigators
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Principal Investigator: Philippe Lambin, Prof. dr. Maastro Clinic, The Netherlands

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Responsible Party: Maastricht Radiation Oncology
ClinicalTrials.gov Identifier: NCT02584400     History of Changes
Other Study ID Numbers: NL50833.068
First Posted: October 22, 2015    Key Record Dates
Last Update Posted: March 8, 2019
Last Verified: March 2019

Keywords provided by Maastricht Radiation Oncology:
prostatic tumors
[18F]HX4 Pet imaging
hypoxia
phase II trial
esophageal tumors
rectal tumors
brain metastases
primary brain tumors

Additional relevant MeSH terms:
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Neoplasms
Neoplasm Metastasis
Hypoxia
Prostatic Neoplasms
Brain Neoplasms
Esophageal Neoplasms
Rectal Neoplasms
Neoplastic Processes
Pathologic Processes
Signs and Symptoms, Respiratory
Signs and Symptoms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Colorectal Neoplasms
Intestinal Neoplasms
Intestinal Diseases