Cervical Cancer, Head and Neck Cancer, Liver Cancer, Lung Cancer, Rectal Cancer
Conditions
Keywords
[F 18]HX4, HX4, Hypoxia, Head/Neck Cancer, Lung Cancer, Liver Cancer, Rectal Cancer, Cervical Cancer, HIF1 alpha, CAIX
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.
Interventions
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
Sponsors
Siemens Molecular Imaging
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
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.
Participants by arm
| Arm | Count |
|---|---|
| [F 18]HX4 \[F 18\]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 | 42 |
| Total | 42 |
Baseline characteristics
| Characteristic | [F 18]HX4 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 16 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants |
| Age Continuous | 59.0 years STANDARD_DEVIATION 9.35 |
| Region of Enrollment Korea, Republic of | 10 participants |
| Region of Enrollment United States | 32 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 42 |
| serious Total, serious adverse events | 0 / 42 |
Outcome results
Primary
Reproducibility of [F18]HX4 PET Imaging in Measuring Hypoxia in Tumors
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
Population: Based upon inclusion/exclusion criteria
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subjects That Received 1st and 2nd [F18] HX4 Scans | Reproducibility of [F18]HX4 PET Imaging in Measuring Hypoxia in Tumors | 39 participants |
Comparison: 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%.p-value: <0.00190% CI: [0.802, 0.929]Pearson's correlation
Comparison: 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%.p-value: <0.00190% CI: [0.792, 0.925]Pearson's correlation
Comparison: 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%.p-value: <0.00190% CI: [0.904, 0.967]Pearson's correlation