Study of [F 18]HX4 Positron Emission Tomography (PET) as a Tool 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.

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