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

• Sponsor: Siemens Molecular Imaging (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01075399
• Collaborator: (none)
• Enrollment: 50
• Arm: 1
• Duration (Months): 24

Study Details

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
• 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: Feb 1, 2010
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: Feb 1, 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 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

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

No locations specified.

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Siemens Molecular Imaging
• ClinicalTrials.gov Identifier: NCT01075399
• Other Study ID Numbers: HX4-200
• First Posted: Feb 25, 2010
• Last Update Posted: Aug 30, 2013
• Last Verified: Jul 1, 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; Imidazole

Study Results

Participant Flow

Recruitment Details	A total of 50 patients were enrolled into the study. There were 42 of 50 patients received at least one dose of [F-18]HX4 and had safety data collected. There were 39 of 50 patients completed two pre-treatment [F-18]HX4 PET/CT scans and were included in analyses to assess reproducibility.

Arm/Group Title	[F 18]HX4
Arm/Group Description	[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
Period Title: Overall Study
STARTED	50
COMPLETED	42
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	[F 18]HX4
Arm/Group Description	[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
Overall Participants	42
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	26 61.9%
>=65 years	16 38.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.0 (9.35)
Sex: Female, Male (Count of Participants)
Female	20 47.6%
Male	22 52.4%
Region of Enrollment (participants) [Number]
Korea, Republic of	10 23.8%
United States	32 76.2%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Based upon inclusion/exclusion criteria

Arm/Group Title	Subjects That Received 1st and 2nd [F18] HX4 Scans
Arm/Group Description	Single arm study. This group includes all subjects that successfully received [F18]HX4 PET scan on 2 separate occasions within 6 days apart to assess reproducibility in measuring tumor hypoxia.
Measure Participants	39
Number [participants]	39 92.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subjects That Received 1st and 2nd [F18] HX4 Scans
	Comments	Primary Tumor SUV max: The reproducibility of [F-18]HX4 uptake in primary tumors was assessed by comparing SUV max of the 1st and 2nd [F18]HX4 PET/CT scan. Estimated power for a range of coefficients of variation (CVs) postulated for the paired differences in SUV values, and for establishing reproducibility within ±20% or ±25%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Significance of probability for no association between the first and second pre-treatment uptake.
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's Correlation Coefficient
	Estimated Value	0.883
	Confidence Interval	(2-Sided) 90%; 0.802 to 0.929
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Subjects That Received 1st and 2nd [F18] HX4 Scans
	Comments	Primary Tumor SUV mean: The reproducibility of [F-18]HX4 uptake in primary tumors was assessed by comparing SUV mean of the 1st and 2nd [F18]HX4 PET/CT scan. Estimated power for a range of coefficients of variation (CVs) postulated for the paired differences in SUV values, and for establishing reproducibility within ±20% or ±25%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Significance of probability for no association between the first and second pre-treatment uptake.
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's Correlation Coefficient
	Estimated Value	0.887
	Confidence Interval	(2-Sided) 90%; 0.792 to 0.925
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Subjects That Received 1st and 2nd [F18] HX4 Scans
	Comments	Primary Tumor to background SUV ratio: The reproducibility of [F-18]HX4 uptake in primary tumors was assessed by comparing tumor to background SUV ratio (T/B) of the 1st and 2nd [F18]HX4 PET/CT scan. Estimated power for a range of coefficients of variation (CVs) postulated for the paired differences in T/B values, and for establishing reproducibility within ±20% or ±25%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Significance of probability for no association between the first and second pre-treatment uptake.
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's Correlation Coefficient
	Estimated Value	0.945
	Confidence Interval	(2-Sided) 90%; 0.904 to 0.967
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	[F 18]HX4
Arm/Group Description	[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
All Cause Mortality
	[F 18]HX4
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	[F 18]HX4
	Affected / at Risk (%)	# Events
Total	0/42 (0%)
Other (Not Including Serious) Adverse Events
	[F 18]HX4
	Affected / at Risk (%)	# Events
Total	0/42 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.