Prostatic NeoplasmsPhase 2HX4 SDNCT02584400
Tumor Hypoxia With HX4 PET in Several Diseases
A Phase 2 study testing Injection with the hypoxia tracer [18F]HX4, in people with Prostatic Neoplasms and Esophageal Neoplasms, run by Maastricht Radiation Oncology at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Prostatic Neoplasms, Esophageal Neoplasms, Neoplasm Metastases, Brain
- What is being tested?
- Injection with the hypoxia tracer [18F]HX4,
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteNetherlands
- Study dates
- May 2016to May 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Recent (< 3 months) myocardial infarction
- Pregnant or breast feeding and willing to take adequate contraceptive measures during the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Non-invasive Imaging of Tumor Hypoxia With [18F]HX4 Positron-Emission-Tomography (PET): A Phase II Trial
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.
Read the 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.
- Conditions
- Prostatic Neoplasms, Esophageal Neoplasms, Neoplasm Metastases, Brain, Rectal Neoplasms, Brain Neoplasm, Primary
- Being tested
- Injection with the hypoxia tracer [18F]HX4,
- Keywords
- prostatic tumors, [18F]HX4 Pet imaging, hypoxia, phase II trial, esophageal tumors, rectal tumors, brain metastases, primary brain tumors
- Medical subject headings
- Prostatic Neoplasms, Esophageal Neoplasms, Neoplasm Metastasis, Rectal Neoplasms, Brain Neoplasms, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Injection with the hypoxia tracer [18F]HX4,Drug
Also called [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
The [18F]HX4 PET scan will be performed, by administrating 444 MBq (12 mCi) [18F]HX4 via a bolus IV injection.
| Study group | Role | What they receive |
|---|---|---|
| [18F]HX4 PET imaging | Experimental | 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 Receives: Drug: Injection with the hypoxia tracer [18F]HX4, |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Visualization of tumor hypoxia with [18F] HX4 PET imaging
Measured: 4 years
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
Quantification of tumor hypoxia with [18F] HX4 PET imaging
Measured: 4 years
Secondary outcomes (6)
Time between [18F] HX4 uptake with local and locoregional tumor recurrence and survival
Exploring the potential relationship of [18F] HX4 uptake with local and locoregional tumor recurrence and survival
Measured: 4 years
Correlation of hypoxia imaging with blood hypoxia markers will be measured by the Pearson or Spearman correlation coefficient
Correlation of hypoxia imaging with blood hypoxia markers
Measured: 4 years
Correlation of hypoxia imaging with tumor tissue biomarkers will be measured by the Pearson or Spearman correlation coefficient
Correlation of hypoxia imaging with tumor tissue biomarkers
Measured: 4 years
Evaluation of tumor hypoxia changes during treatment by comparison of the PET uptake values in the tumor, measured before and during treatment
Evaluation of tumor hypoxia changes during treatment
Measured: 4 years
Spatial correlation of [18F] HX4-PET with imaging pre-treatment using a correlation coefficient
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
Measured: 4 years
Spatial correlation of [18F] HX4-PET with imaging three months after treatment using a correlation coefficient
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
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2015 (estimated)
- Study startMay 2016
- Primary completionMay 2017
- Study completionMay 2017
Why it stopped: patients did not want to participate
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostatic NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht Radiation Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Philippe Lambin, Prof. dr., Principal investigator, Maastro Clinic, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02584400
- Sponsor's protocol ID
- NL50833.068
- Acronym
- HX4 SD
- Status last verified
- Mar 2019
- First submitted
- 7 Oct 2015
- Last updated
- 8 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Imaging of Tumor Hypoxia With [18F]HX4 Positron-Emission-Tomography (PET): A Phase II Trial
- ClinicalTrials.gov ID
- NCT02584400
- Acronym / sponsor ID
- HX4 SD / NL50833.068
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: patients did not want to participate
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Maastricht Radiation OncologyUniversity, hospital or other
- Study start
- May 2016
- Primary completion
- May 2017 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 22 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| [18F]HX4 PET imaging | Experimental | Drug: Injection with the hypoxia tracer [18F]HX4,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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (2 listed)
- Recent (< 3 months) myocardial infarction
- Pregnant or breast feeding and willing to take adequate contraceptive measures during the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Injection with the hypoxia tracer [18F]HX4,Also: [18F]HX4 is 3-[18F]fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)propan-1-olThe [18F]HX4 PET scan will be performed, by administrating 444 MBq (12 mCi) [18F]HX4 via a bolus IV injection. | Drug | [18F]HX4 PET imaging |
Primary outcome
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
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
6 secondary outcomes
Time between [18F] HX4 uptake with local and locoregional tumor recurrence and survival
Time frame: 4 years
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 tumor tissue biomarkers will be measured by the Pearson or Spearman correlation coefficient
Time frame: 4 years
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
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 three months after treatment using a correlation coefficient
Time frame: 3 months
Results and safety
The study was stopped early (reason given: patients did not want to participate). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philippe Lambin, Prof. dr. principal investigator
Maastro Clinic, The Netherlands
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Injection with the hypoxia tracer [18F]HX4, in people with Prostatic Neoplasms and Esophageal Neoplasms, run by Maastricht Radiation Oncology at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: patients did not want to participate). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: 4 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2019.