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

• ClinicalTrials.gov Identifier: NCT01075399
• Recruitment Status: Completed
• First Posted: February 25, 2010
• Results First Posted: August 30, 2013
• Last Update Posted: August 30, 2013
• Sponsor: Siemens Molecular Imaging
• Information provided by (Responsible Party): Siemens Molecular Imaging

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Head and Neck Cancer; Lung Cancer; Liver Cancer; Rectal Cancer; Cervical Cancer	Drug: [F 18]HX4	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Official Title: A Pilot, Phase II , Open Label, Nonrandomized, Multi- Center Study of [F 18]HX4 Positron Emission Tomography (PET) to Detect Hypoxia in Tumors
• Study Start Date: February 2010
• Actual Primary Completion Date: May 2011
• Actual Study Completion Date: February 2012

Arms and Interventions

Arm

Intervention/treatment

Experimental: [F 18]HX4; [F18]HX4, 10 mCi, is administered in a single intravenous bolus injection, followed by a saline flush.

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

Outcome Measures

Primary Outcome Measures :

1. Reproducibility of [F18]HX4 PET Imaging in Measuring Hypoxia in Tumors [ Time Frame: Time between 1st and 2nd scan was 1 to 6 days ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Sponsors and Collaborators

Siemens Molecular Imaging

Investigators

• 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

More Information

• Responsible Party: Siemens Molecular Imaging
• ClinicalTrials.gov Identifier: NCT01075399
• Other Study ID Numbers: HX4-200
• First Posted: February 25, 2010
• Results First Posted: August 30, 2013
• Last Update Posted: August 30, 2013
• Last Verified: July 2013

Keywords provided by Siemens Molecular Imaging:

[F 18]HX4; HX4; Hypoxia; Head/Neck Cancer; Lung Cancer; Liver Cancer; Rectal Cancer; Cervical Cancer; HIF1 alpha; CAIX

Additional relevant MeSH terms:

Rectal Neoplasms; Head and Neck Neoplasms; Uterine Cervical Neoplasms; Liver Neoplasms; Hypoxia; Neoplasms by Site; Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Liver Diseases; Signs and Symptoms, Respiratory; Imidazole; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action