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

Phase 2

Completed

• Conditions: Rectal Cancer; Lung Cancer; Cervical Cancer; Liver Cancer; Head and Neck Cancer
• Interventions: Drug: [F 18]HX4

• Registration Number: NCT01075399
• Lead Sponsor: Siemens Molecular Imaging

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.

Study Timeline

• Study Start: 2010-02
• Study First Submitted: 2010-02-23
• Study First Submitted QC: 2010-02-23
• Study First Posted: 2010-02-25
• Primary Completion: 2011-05
• Study Completion: 2012-02
• Results First Submitted: 2013-02-14
• Status Verified: 2013-07
• Results First Submitted QC: 2013-07-26
• Last Update Submitted: 2013-07-26
• Results First Posted: 2013-08-30
• Last Update Posted: 2013-08-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
[F 18]HX4	[F 18]HX4	\[F18\]HX4, 10 mCi, is administered in a single intravenous bolus injection, followed by a saline flush.

Primary Outcome Measures

Name	Time	Method
Reproducibility of [F18]HX4 PET Imaging in Measuring Hypoxia in Tumors	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.