Study of [F 18]HX4 Positron Emission Tomography (PET) as a Tool to Detect Hypoxia in Tumors (HX4-200)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Siemens Molecular Imaging
ClinicalTrials.gov Identifier:
NCT01075399
First received: February 23, 2010
Last updated: July 26, 2013
Last verified: July 2013

February 23, 2010
July 26, 2013
February 2010
May 2011   (final data collection date for primary outcome measure)
Reproducibility of [F18]HX4 PET Imaging in Measuring Hypoxia in Tumors [ Time Frame: Time between 1st and 2nd scan was 1 to 6 days ] [ Designated as safety issue: No ]
Primary tumor uptake of [F 18]HX4 was measured on PET images by onsite radiologist or nuclear medicine physician for 1st and 2nd PET scans. Values measured were: SUV (Standard Uptake Value), SUV Max (Maximum standard uptake value), SUV Mean (Mean standard uptake value), and T/B ratio (Tumor to background ratio). Pearson's correlation coefficient was calculated for each of the parameter.
  • To evaluate two sequential pre-treatment [F 18]HX4 PET scans (recommended to be within 48 hours of each other) in order to assess reproducibility and reliability of [F 18]HX4 PET imaging for measuring hypoxia in tumors [ Time Frame: (3) or (4) visits over a period of approximately 6 weeks ] [ Designated as safety issue: No ]
  • To compare [F 18]HX4 PET/CT imaging with tissue immunohistochemistry staining using specific antibodies for HIF1alpha and /or CA-IX in order to assess the presence of hypoxia in tumor [ Time Frame: (3) or (4) visits over a period of approximately 6 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01075399 on ClinicalTrials.gov Archive Site
Not Provided
  • To collect vital signs, ECG, routine laboratory data and adverse events before the first pre-treatment [F 18]HX4 PET and after the second pre-treatment administration of [F 18]HX4 [ Time Frame: (3) or (4) visits over a period of approximately 6 weeks ] [ Designated as safety issue: Yes ]
  • To establish a threshold value of tumor/background (T/B) ratio for [F 18]HX4 PET/CT imaging of hypoxic tissue [ Time Frame: (3) or (4) visits over a period of approximately 6 weeks ] [ Designated as safety issue: No ]
  • To examine the standard uptake values (SUV) and T/B changes of [F 18]HX4 PET/CT imaging before treatment and after mid-treatment for patients that have one or more tumors with a T/B ratio ≥ 1.3 on both pre-treatment [F 18]HX4 PET/CT imaging scans [ Time Frame: (3) or (4) visits over a period of approximately 6 weeks ] [ Designated as safety issue: No ]
  • To gain clinical experience and information to guide the design of a future, pivotal Phase II trial(s) [ Time Frame: (3) or (4) visits over a period of approximately 6 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study of [F 18]HX4 Positron Emission Tomography (PET) as a Tool to Detect Hypoxia in Tumors
A Pilot, Phase II , Open Label, Nonrandomized, Multi- Center Study of [F 18]HX4 Positron Emission Tomography (PET) to Detect Hypoxia in Tumors

This pilot phase II study is designed as a test and retest study to investigate [F 18]HX4 as a reliable non-invasive PET imaging marker for detection of tumor hypoxia regions and to establish a threshold for [F 18]HX4 uptake in the tumor. The study will evaluate the relationship between hypoxia biomarkers (HIF1α and CA-IX) by immunohistochemistry (IHC) and tumor uptake of [F 18]HX4 by PET imaging.

A Pilot Phase II Study

The primary objectives for this study are:

  • To test the reproducibility of [F-18] HX-4 uptake in tumors by imaging the same patient on sequential days in a test-retest protocol
  • To test and confirm the relationship between hypoxia in tumors measured by hypoxia related biomarkers (HIF1α and CA-IX) with immunohistochemistry (IHC) and regional [F-18 HX-4] uptake in tumors with PET/CT.

The secondary objectives for this study are:

  • To continue safety evaluation by the collection of safety data from all patients
  • To establish the threshold for hypoxia uptake in [F- 18]HX4 PET imaging
  • To collect data to test [F-18]HX4 PET imaging as a predictor of response in a subgroup of patients receiving treatment
  • To gain experience with [F-18]HX4 PET/CT in order to improve the study design to conduct future studies

Design: An open label, non-randomized, uncontrolled, single group assignment, pilot efficacy study

Procedures: Informed consent, collection of demographic information, medical history, blood labs, physical examination, vital signs, ECGs, two or three sets of [F-18]HX4 dosing and imaging scans including two pretreatment, and one mid-treatment if [F-18]HX4 tumor/background ratio ≥ 1.3 from pre-treatment scans, one pre-treatment [F-18]FDG, one mid-treatment if [F- 18]HX4 tumor/background ratio ≥1.3 from pre-treatment scans, concomitant medication collection, adverse event monitoring, and assessment of tumor response to treatment

Patients: Approximately forty (40) patients who have diagnosis confirmed by histopathological examination of tumor tissue from head/neck, lung, liver, rectal or cervical cancers and will receive chemotherapy, radiation therapy or chemoradiotherapy. This allows for approximately 30 evaluable patients to complete this study at approximately six sites.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
  • Head and Neck Cancer
  • Lung Cancer
  • Liver Cancer
  • Rectal Cancer
  • Cervical Cancer
Drug: [F 18]HX4
Approximately forty (40) patients who have diagnosis confirmed by histopathological examination of tumor tissue from head/neck, lung, liver, rectal or cervical cancers and will receive chemotherapy, radiation therapy or chemoradiotherapy, will be imaged under PET/CT with [F 18]HX4
Other Names:
  • [F-18]HX4
  • 3-[18F]fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)
  • -1H-1,2,3-triazol-1-yl)-propan-1-ol
Experimental: [F 18]HX4
[F18]HX4, 10 mCi, is administered in a single intravenous bolus injection, followed by a saline flush.
Intervention: Drug: [F 18]HX4
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
50
February 2012
May 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patient is >18 years and male or female of any race / ethnicity
  • Patient or patient's legally acceptable representative provides written informed consent and is willing to comply with protocol procedures
  • Patient must have histopathologically confirmed head/neck, lung, liver, rectal or cervical cancer with tumor size ≥ 3cm
  • Patient has tumor tissue samples available before treatment for future immunohistochemistry biomarker tests (HIF1alpha and CA-IX)
  • Patient is scheduled to have or already had a clinical [F 18]FDG PET/CT scan recommended to be within 14 days of the first pre-treatment [F 18]HX4 PET/CT scan and have no treatment intervention in between these two scans
  • Patient is scheduled or is intended to be scheduled to receive chemotherapy, radiation or chemoradiotherapy treatment(s) after the pre-treatment [F 18]HX4 PET/CT and [F 18]FDG PET/CT scans for his/her cancer care
  • Patient must have hepatic and renal functions as defined by laboratory results within the following ranges:

    • Total bilirubin within 2 times institutional upper limit of normal
    • AST (SGOT) and ALT (SGPT) ≤ 2.5 times institutional upper limits of normal
    • Serum creatinine ≤ 2.5 times institutional limit of normal
    • BUN within 2 times institutional upper limit of normal

Exclusion Criteria:

  • Patient is not capable of complying with study procedures
  • Female patient is pregnant or nursing

    o Exclude the possibility of pregnancy by one of the following:

    • Confirming in medical history that the patient is post-menopausal for a minimum of one year, or surgically sterile
    • Confirming the patient is using one of the following methods of birth control for a minimum of one month prior to entry into this study: IUD, oral contraceptives, Depo-Provera, or Norplant
    • Confirming a negative urine dipstick test taken the morning of but before receiving [F 18]HX4
  • Patient has been involved in an investigative, radioactive research procedure within 7 days and during the study participation period
  • Patient has any other condition or personal circumstance that, in the judgment of the investigator, might interfere with the collection of complete data
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01075399
HX4-200
No
Siemens Molecular Imaging
Siemens Molecular Imaging
Not Provided
Principal Investigator: Jacqueline Brunetti, MD Holy Name Hospital
Principal Investigator: Orhan Nalcioglu, PhD University of California Irvine Medical Center, Orange, CA
Principal Investigator: Alan Waxman, MD Cedars-Sinai Medical Center, Los Angeles, CA
Principal Investigator: Kyung-Han Lee, MD Sungkyunkwan University School of Medicine, Samsung Medical Center, Gangnam-gu, Seoul, Korea
Principal Investigator: Dae-Hyuk Moon, MD University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Seoul, Korea
Principal Investigator: Scott Dessain, MD, PhD Lankenau Institute for Medical Research, Wynnewood, PA and Bryn Mawr Hospital Outpatient Imaging Center, Bryn Mawr, PA
Principal Investigator: Rathan Subamaniam, MD Boston Medical Center, Boston, MA
Principal Investigator: Shyam Srinivas, MD, PhD Cleveland Clinic, Cleveland, OH
Principal Investigator: Nasrin Ghesani, MD University of Medicine and Dentistry of New Jersey, NJMS-UH/UMDNJ Cancer Center, and University Heights Advanced Imaging Center, Newark, NJ
Principal Investigator: John M Buatti, MD University of Iowa Hospitals and Clinics, Carver College of Medicine, and Holden Comprehensive Cancer Center,Iowa City, Iowa
Siemens Molecular Imaging
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP