Tumor Hypoxia With HX4 PET in Several Diseases

NCT02584400 | Terminated Phase 2 DMC

• 1 other identifier: NL50833.068
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• 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

  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

  4 years

Secondary Outcomes (6)

• Time between [18F] HX4 uptake with local and locoregional tumor recurrence and survival

  4 years

• Correlation of hypoxia imaging with blood hypoxia markers will be measured by the Pearson or Spearman correlation coefficient

  4 years

• Correlation of hypoxia imaging with tumor tissue biomarkers will be measured by the Pearson or Spearman correlation coefficient

  4 years

• Evaluation of tumor hypoxia changes during treatment by comparison of the PET uptake values in the tumor, measured before and during treatment

  4 years

• Spatial correlation of [18F] HX4-PET with imaging pre-treatment using a correlation coefficient

  4 years

Study Arms (1)

[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

Drug: Injection with the hypoxia tracer [18F]HX4,

Interventions

Injection with the hypoxia tracer [18F]HX4, DRUG

The \[18F\]HX4 PET scan will be performed, by administrating 444 MBq (12 mCi) \[18F\]HX4 via a bolus IV injection.

Also known as: [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

[18F]HX4 PET imaging

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• years or older
• Have given written informed consent before patient registration

You may not qualify if:

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

Sponsors & Collaborators

• Maastricht Radiation Oncology: lead

Study Sites (1)

MAASTRO Clinic

Maastricht, Limburg, 6202 NA, Netherlands

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Esophageal Neoplasms; Neoplasm Metastasis; Rectal Neoplasms; Brain Neoplasms; Hypoxia

Interventions

Injections; 3-fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)propan-1-ol

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Colorectal Neoplasms; Intestinal Neoplasms; Intestinal Diseases; Rectal Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Philippe Lambin, Prof. dr.

  Maastro Clinic, The Netherlands

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2015
• First Posted: October 22, 2015
• Study Start: May 1, 2016
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: March 8, 2019

Record last verified: 2019-03

Locations

NL (1)