Clinical trial NCT01075399: Study of [F 18]HX4 Positron Emission Tomography (PET) as a Tool to Detect Hypoxia in Tumors
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Lung Cancer
Liver Cancer
Rectal Cancer
Cervical Cancer
Keywords: [F 18]HX4
HX4
Hypoxia
Head/Neck Cancer
Lung Cancer
Liver Cancer
Rectal Cancer
Cervical Cancer
HIF1 alpha
CAIX
Lead sponsor: Siemens Molecular Imaging
Sponsor class: INDUSTRY
First posted: 2010-02-25
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

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.

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.

Eligibility 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

Primary outcomes:
measure: Reproducibility of [F18]HX4 PET Imaging in Measuring Hypoxia in Tumors
timeFrame: Time between 1st and 2nd scan was 1 to 6 days
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Holy Name Hospital
name: Jacqueline Brunetti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California Irvine Medical Center, Orange, CA
name: Orhan Nalcioglu, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cedars-Sinai Medical Center, Los Angeles, CA
name: Alan Waxman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sungkyunkwan University School of Medicine, Samsung Medical Center, Gangnam-gu, Seoul, Korea
name: Kyung-Han Lee, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Seoul, Korea
name: Dae-Hyuk Moon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lankenau Institute for Medical Research, Wynnewood, PA and Bryn Mawr Hospital Outpatient Imaging Center, Bryn Mawr, PA
name: Scott Dessain, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Medical Center, Boston, MA
name: Rathan Subamaniam, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cleveland Clinic, Cleveland, OH
name: Shyam Srinivas, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Medicine and Dentistry of New Jersey, NJMS-UH/UMDNJ Cancer Center, and University Heights Advanced Imaging Center, Newark, NJ
name: Nasrin Ghesani, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Iowa Hospitals and Clinics, Carver College of Medicine, and Holden Comprehensive Cancer Center,Iowa City, Iowa
name: John M Buatti, MD
role: PRINCIPAL_INVESTIGATOR
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