Liver CancerPhase 2NCT02471313

Integrated Imaging Strategy to Phenotype Progression of Liver Tumors During and After Chemoembolization

A Phase 2 study testing [18F] FMISO in people with Liver Cancer and Liver Neoplasm, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Background: Treatment for liver cancer can include surgery, transplant, and chemotherapy. It can also include other minimally invasive tumor treatments such as transarterial chemoembolization (TACE). TACE treatment for liver cancer helps control the cancer but is not considered a cure. Read more about this study

Who is it for?: Ages 18 to 99 years
Conditions the study is for: Liver Cancer, Liver Neoplasm, Hepatocellular Carcinoma
What is being tested?: [18F] FMISO
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 3 participants
Where: 1 siteUnited States
Study dates: 12 Jun 2015to 7 Mar 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 99 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients must have confirmed inoperable primary hepatic malignancy or hepatic dominant metastatic - neoplastic disease evidenced by histology or cytology, or characteristic enhancement pattern on CT or MRI together with an abnormal serum alpha-fetoprotein >200mg/dl in the case of hepatocellular carcinoma.
Patients with hepatocellular carcinoma should conform to intermediate stage disease according to the BCLC(16) staging system (Stage A4 or B) and be otherwise eligible to receive TACE treatment.
Patients must have had no chemotherapy or radiotherapy to the liver therapy for, their malignancy for at least 2 weeks (or until response can be adequately assessed) prior to treatment and must have recovered from all clinically significant side effects of therapeutic and diagnostic interventions.
Serum creatinine less than or equal to 2.0 mg/dl unless the measured creatinine clearance is greater than 60ml/min
Age greater than or equal to18 years
Ability of subject to understand and willingness to sign a written informed consent document

Show all 11Show fewer

Patient must be able to lie still for the procedure
ECOG status less than or equal to 2
In addition, for patients receiving TACE outside NIH:
Patient must have physician willing to collaborate with NIH PI by providing required medical record and digital MR/ CT scan documentation pre and post TACE procedure.
Patient must be willing to sign an Authorization for the Release of Medical Information form

Who cannot join

Patients who have received prior TACE treatment
History of allergic reactions attributed to compounds of similar chemical or biologic composition to misonidazole or other agents used in study.
Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Patients of childbearing age must not be pregnant. The effects of [(18)F]FMISO on the developing human fetus are unknown. Pregnancy is a contraindication for TACE.

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Pilot Study of an Integrated Imaging Strategy to Phenotype Progression of Liver Tumors During and After Chemoembolization

Background:

Treatment for liver cancer can include surgery, transplant, and chemotherapy. It can also include other minimally invasive tumor treatments such as transarterial chemoembolization (TACE). TACE treatment for liver cancer helps control the cancer but is not considered a cure. Researchers want to learn more about the effects of TACE on liver tumors and surrounding tissue. To do this, they will use a positive emission test (PET) and a radioactive tracer called [18F] FMISO.

Objectives:

To see if [18F] FMISO is useful for evaluating what happens to liver tumors and surrounding tissue after TACE.

Eligibility:

People age 18 and older with liver cancer who have been approved to have TACE.

Design:

Participants will meet with a study researcher to see if they can take part in the study.
Participants will have TACE under a separate NCI protocol or at a hospital other than the NIH Clinical Center.
Before and after TACE, participants will have a CT and MRI of the abdomen. For these scans, they will lie in a machine that takes pictures of their body. They will also have blood tests and a physical exam.
The [18F] FMISO imaging study will be performed at NIH only.
Participants will have an intravenous catheter placed in their arm (if they do not have one). The [18F] FMISO tracer will be injected.
Participants will have PET-CT scans. Each scan will take about 30 minutes.
Some participants will also have [18F] FMISO and PET-CT scans before TACE.
As part of standard care for TACE, participants will have CT and MRI scans at regular intervals. This will evaluate tumor response.

Read the detailed description

Background

TACE is the standard therapy for inoperable primary liver cancers or tumor control prior to transplantation. The mechanisms for TACE s failure remains poorly understood.
Although acute hypoxia and significant tumor necrosis occurs following TACE, the tumor adaptive response and localization for such have not been well characterized.
Imaging tools using a hypoxia-specific tracer [(18)F] FMISO may help identify the pattern and distribution of acute post-TACE tumor hypoxia relative to demonstrated tumor progression.
The primary hypothesis of this study states that tumor progression post-TACE arises from changes in tumor phenotype induced by treatment-related hypoxia superimposed on the dynamic process of underlying tumor hypoxia.

Objectives

-To determine the feasibility of hypoxic tumor identification despite relatively high liver background signal, and describe patterns of tumor hypoxia in the immediate post-TACE treatment period using PET imaging [(18)F] MISO uptake registered with cross-sectional imaging.

Eligibility

Patients greater than or equal to 18 years with inoperable primary hepatic malignancy or hepatic-dominant metastatic-disease and be otherwise eligible to receive TACE treatment. Patients with hepatocellular carcinoma should have intermediate stage disease according to the BCLC staging system (Stage A4 or B).
Patients must not have had chemotherapy- or radiation therapy to liver for at least 2 weeks prior to starting study treatments.
Patients must not have an acute, critical illness.
Patients must not be pregnant
Able to understand and be willing to sign a written informed consent

Design

Fifteen patients with primary or metastatic liver malignancy will be enrolled into this pilot, non-randomized, open study of the feasibility of using (18)F-fluoromisonidazole PET scanning to determine hypoxic tumor identification and localization, and to identify the pattern and distribution of acute post-TACE tumor hypoxia relative to demonstrated tumor progression.
Twenty-four to seventy-two hours after standard of care TACE, patients will undergo

PET scanning using 0.1mCi/kg (maximum 10mCi) of (18)F-fluoromisonidazole [(18)F] MISO).

Conditions: Liver Cancer, Liver Neoplasm, Hepatocellular Carcinoma, HCC
Being tested: [18F] FMISO
Keywords: Cross-Sectional Imaging, Chemoembolization, Radiation Therapy, Tumor Hypoxia, PET Imaging
Medical subject headings: Liver Neoplasms, Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

[18F] FMISODrug
Also called FMISO
[18F] Fluromisonidazole, 1 h-(3-[18F]-fluro-2hydroxyl-propy10-2-nitro-imidazaole is an investigational positron emission tomography (PET) radiopharmaceutical for injection and used to visualize hypoxia imaging agent. Each patient will receive up to 10 mCi of [18F] FMISO PET imaging post TACE procedure.

Study groups in NCT02471313
Study group	Role	What they receive
[18F] FMISO PET scan	Experimental	Patients with primary hepatic malignancy who underwent [18F] FMISO PET Scan following transarterial chemoembolization (TACE) procedure Receives: Drug: [18F] FMISO

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants for Which Uptake of [18F]-FMISO Was Successful and Hypoxic Tumors Were Observed During PET Scan Imaging Post TACE Procedure
A single dose of study imaging agent [18F] FMISO was administered following the TACE procedure. PET Scan imaging was then performed to evaluate if hypoxic tumor identification were observable following administration of study imaging agent. Power and significance calculations are not applicable to this small sample feasibility study.
Measured: up to 72 hours after injection of [18F] FMISO

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Jun 20157 Mar 2018

First posted15 Jun 2015 (estimated)
Study start12 Jun 2015
Primary completion7 Mar 2018
Study completion7 Mar 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Liver CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 3 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02471313
Sponsor's protocol ID: 150137
Other IDs: NCT02471313, 15-CC-0137
Status last verified: 7 Mar 2018
First submitted: 12 Jun 2015
Last updated: 23 Apr 2019
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes

Publications

THOMLINSON RH, GRAY LH. The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer. 1955 Dec;9(4):539-49. doi: 10.1038/bjc.1955.55. No abstract available.
PubMed 13304213
Vaupel P, Mayer A, Hockel M. Tumor hypoxia and malignant progression. Methods Enzymol. 2004;381:335-54. doi: 10.1016/S0076-6879(04)81023-1. No abstract available.
PubMed 15063685
Durand RE, Aquino-Parsons C. Non-constant tumour blood flow--implications for therapy. Acta Oncol. 2001;40(7):862-9. doi: 10.1080/02841860152703508.
PubMed 11859987

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 23 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Study of an Integrated Imaging Strategy to Phenotype Progression of Liver Tumors During and After Chemoembolization
ClinicalTrials.gov ID: NCT02471313
Acronym / sponsor ID: 150137
Conditions: Liver Cancer, Liver Neoplasm, Hepatocellular Carcinoma, HCC
Keywords: Cross-Sectional Imaging, Chemoembolization, Radiation Therapy, Tumor Hypoxia, PET Imaging
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 3 participants (actual)
Lead sponsor: National Institutes of Health Clinical Center (CC)US National Institutes of Health
Study start: 12 Jun 2015
Primary completion: 7 Mar 2018 (actual)
Study completion: 7 Mar 2018 (actual)
First posted: 15 Jun 2015 (estimated)
Results: Posted 23 Apr 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Background:

Treatment for liver cancer can include surgery, transplant, and chemotherapy. It can also include other minimally invasive tumor treatments such as transarterial chemoembolization (TACE). TACE treatment for liver cancer helps control the cancer but is not considered a cure. Researchers want to learn more about the effects of TACE on liver tumors and surrounding tissue. To do this, they will use a positive emission test (PET) and a radioactive tracer called [18F] FMISO.

Objectives:

To see if [18F] FMISO is useful for evaluating what happens to liver tumors and surrounding tissue after TACE.

Eligibility:

People age 18 and older with liver cancer who have been approved to have TACE.

Design:

Participants will meet with a study researcher to see if they can take part in the study.
Participants will have TACE under a separate NCI protocol or at a hospital other than the NIH Clinical Center.
Before and after TACE, participants will have a CT and MRI of the abdomen. For these scans, they will lie in a machine that takes pictures of their body. They will also have blood tests and a physical exam.
The [18F] FMISO imaging study will be performed at NIH only.
Participants will have an intravenous catheter placed in their arm (if they do not have one). The [18F] FMISO tracer will be injected.
Participants will have PET-CT scans. Each scan will take about 30 minutes.
Some participants will also have [18F] FMISO and PET-CT scans before TACE.
As part of standard care for TACE, participants will have CT and MRI scans at regular intervals. This will evaluate tumor response.

Detailed description

Background

TACE is the standard therapy for inoperable primary liver cancers or tumor control prior to transplantation. The mechanisms for TACE s failure remains poorly understood.
Although acute hypoxia and significant tumor necrosis occurs following TACE, the tumor adaptive response and localization for such have not been well characterized.
Imaging tools using a hypoxia-specific tracer [(18)F] FMISO may help identify the pattern and distribution of acute post-TACE tumor hypoxia relative to demonstrated tumor progression.
The primary hypothesis of this study states that tumor progression post-TACE arises from changes in tumor phenotype induced by treatment-related hypoxia superimposed on the dynamic process of underlying tumor hypoxia.

Objectives

Eligibility

Patients greater than or equal to 18 years with inoperable primary hepatic malignancy or hepatic-dominant metastatic-disease and be otherwise eligible to receive TACE treatment. Patients with hepatocellular carcinoma should have intermediate stage disease according to the BCLC staging system (Stage A4 or B).
Patients must not have had chemotherapy- or radiation therapy to liver for at least 2 weeks prior to starting study treatments.
Patients must not have an acute, critical illness.
Patients must not be pregnant
Able to understand and be willing to sign a written informed consent

Design

Fifteen patients with primary or metastatic liver malignancy will be enrolled into this pilot, non-randomized, open study of the feasibility of using (18)F-fluoromisonidazole PET scanning to determine hypoxic tumor identification and localization, and to identify the pattern and distribution of acute post-TACE tumor hypoxia relative to demonstrated tumor progression.
Twenty-four to seventy-two hours after standard of care TACE, patients will undergo

PET scanning using 0.1mCi/kg (maximum 10mCi) of (18)F-fluoromisonidazole [(18)F] MISO).

Study design

Primary purpose: Diagnosis
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
[18F] FMISO PET scan	Experimental	Drug: [18F] FMISOPatients with primary hepatic malignancy who underwent [18F] FMISO PET Scan following transarterial chemoembolization (TACE) procedure

Who may qualify

Ages: 18 to 99 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Patients must have confirmed inoperable primary hepatic malignancy or hepatic dominant metastatic - neoplastic disease evidenced by histology or cytology, or characteristic enhancement pattern on CT or MRI together with an abnormal serum alpha-fetoprotein >200mg/dl in the case of hepatocellular carcinoma.
Patients with hepatocellular carcinoma should conform to intermediate stage disease according to the BCLC(16) staging system (Stage A4 or B) and be otherwise eligible to receive TACE treatment.
Patients must have had no chemotherapy or radiotherapy to the liver therapy for, their malignancy for at least 2 weeks (or until response can be adequately assessed) prior to treatment and must have recovered from all clinically significant side effects of therapeutic and diagnostic interventions.
Serum creatinine less than or equal to 2.0 mg/dl unless the measured creatinine clearance is greater than 60ml/min
Age greater than or equal to18 years

Key exclusion criteria (5 listed)

Patients who have received prior TACE treatment
History of allergic reactions attributed to compounds of similar chemical or biologic composition to misonidazole or other agents used in study.
Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Patients of childbearing age must not be pregnant. The effects of [(18)F]FMISO on the developing human fetus are unknown. Pregnancy is a contraindication for TACE.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
[18F] FMISOAlso: FMISO[18F] Fluromisonidazole, 1 h-(3-[18F]-fluro-2hydroxyl-propy10-2-nitro-imidazaole is an investigational positron emission tomography (PET) radiopharmaceutical for injection and used to visualize hypoxia imaging agent. Each patient will receive up to 10 mCi of [18F] FMISO PET imaging post TACE procedure.	Drug	[18F] FMISO PET scan

Primary outcome

Number of Participants for Which Uptake of [18F]-FMISO Was Successful and Hypoxic Tumors Were Observed During PET Scan Imaging Post TACE Procedure
Time frame: up to 72 hours after injection of [18F] FMISO
A single dose of study imaging agent [18F] FMISO was administered following the TACE procedure. PET Scan imaging was then performed to evaluate if hypoxic tumor identification were observable following administration of study imaging agent. Power and significance calculations are not applicable to this small sample feasibility study.

Results and safety

Results posted to the registry on 23 Apr 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
[18F] FMISO PET Scan	3	3

Primary outcome: Number of Participants for Which Uptake of [18F]-FMISO Was Successful and Hypoxic Tumors Were Observed During PET Scan Imaging Post TACE Procedure

Time frame: up to 72 hours after injection of [18F] FMISO. Count of participants. Unit: Participants

Measure	Uptake of [18F] FMISO With PET Scan Imaging n = 3
Value	0

Adverse events

Time frame: Adverse event data were collected within 24 hours post [18F] FMISO injection on all study participants. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
[18F] FMISO PET Scan	0 of 3 (0%)	1 of 3 (33.3%)	0 of 3

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 13304213THOMLINSON RH, GRAY LH. The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer. 1955 Dec;9(4):539-49. doi: 10.1038/bjc.1955.55. No abstract available.
Background: PubMed 15063685Vaupel P, Mayer A, Hockel M. Tumor hypoxia and malignant progression. Methods Enzymol. 2004;381:335-54. doi: 10.1016/S0076-6879(04)81023-1. No abstract available.
Background: PubMed 11859987Durand RE, Aquino-Parsons C. Non-constant tumour blood flow--implications for therapy. Acta Oncol. 2001;40(7):862-9. doi: 10.1080/02841860152703508.
NIH Clinical Center Detailed Web PageLink provided by the sponsor.

Related trials for Liver Cancer

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Elliot B Levy, M.D. principal investigator

National Institutes of Health Clinical Center (CC)

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing [18F] FMISO in people with Liver Cancer and Liver Neoplasm, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants for Which Uptake of [18F]-FMISO Was Successful and Hypoxic Tumors Were Observed During PET Scan Imaging Post TACE Procedure (time frame: up to 72 hours after injection of [18F] FMISO). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02471313, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2019.