Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Hematinics

All Drugs and Chemicals

Liver Extracts

TKM-080301

Protein Kinase Inhibitors

Enzyme Inhibitors

Phase 1 - dose escalation with intravenous infusion of TKM-080301 to determine MTD.

Phase 2 - dose expansion at the MTD.

Mark Kowalski, M.D., Ph.D.

This study is an open-label, multi-center, phase 1, dose escalation study with a phase 2 expansion cohort to determine the safety, pharmacokinetics and preliminary anti-tumor activity of intravenous TKM-080301 in subjects with advanced hepatocellular carcinoma (HCC).

This study is being done to:

* Test the safety and tolerability of TKM-080301 in subjects with advanced hepatocellular carcinoma
* Find the highest dose of TKM-080301 that can be given without causing side effects, called the maximum tolerated dose (MTD).
* Provide a preliminary assessment of anti-tumor activity of TKM-080301

Study design: Open label, multi-center, 3 + 3 dose-escalation study with an expansion cohort at the maximum tolerated dose (MTD) to investigate safety, tolerability, PK, and preliminary anti-tumor activity of TKM 080301 in subjects with HCC.

Sequential cohorts of 3 to 6 subjects will receive escalating doses of TKM 080301 according to a pre-specified dose escalation scheme. Assessment of dose-limiting toxicities (DLTs) will be made during Cycle 1 to determine the maximum tolerated dose (MTD). Once the MTD level is established, approximately 20 subjects will be enrolled in an expansion cohort to further confirm the safety and tolerability of TKM-080301 at the MTD.

Study Population: A minimum of 9 and up to approximately 18 adult male or female subjects with histologically or cytologically confirmed metastatic or locally advanced inoperable HCC and a life expectancy of 3 months or more are planned in the dose escalation phase. Approximately 20 subjects are planned in the expansion cohort.

Study Treatment: TKM-080301 will be administered by intravenous (IV) infusion, once weekly for 3 consecutive weeks followed by a 1 week rest period. This 28-day treatment period constitutes 1 cycle.

Subjects who demonstrate clinical benefit without progression per RECIST 1.1 guidelines may receive treatment beyond 6 cycles if the Investigator considers it is in the best interest of the subject, and only with the approval of the Medical Monitor. Subjects would then continue TKM 080301 therapy until withdrawal of consent, disease progression or unacceptable toxicity occurs.

Pharmacokinetics (PK) Subjects will undergo blood sample collection for PK analysis during cycles 1 and 2.

Study Duration: Each treatment cycle will have duration of 28 days and each subject will typically receive up to 6 cycles of treatment. The total duration of the study is expected to be approximately 28 months.

Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Intravenous TKM-080301 in Subjects With Advanced Hepatocellular Carcinoma

Open-Label, Multi-Center, Phase 1, Dose Escalation Study With Phase 2 Expansion Cohort to Determine the Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Intravenous TKM-080301 in Subjects With Advanced Hepatocellular Carcinoma

Assessment of target mRNA reduction in participants consenting to pre- and post-treatment tumor biopsies.

Obtain preliminary assessment of anti-tumor activity by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)

Arbutus Biopharma Corporation

In patients randomized to receive the experimental therapy, transarterial embolization (TAE) treatments will be initiated within one week of randomization. Blunt embolization will be performed with LC beads with a maximum size of 700 µm. Microwave ablation (MWA) will be performed up to one month following randomization. The LC beads will be admixed with 8-15 mL of contrast and injected into the arterial branch at a rate of 1-2 mL/min. Treatment may be discontinued if any exclusion criteria develop in the patient or at the patient's request.

Microwave ablation (MWA) will be performed up to one month following randomization. Treatment may be discontinued if any exclusion criteria develop in the patient or at the patient's request. All operative MWAs will be performed in a laparoscopic or robot-assisted laparoscopic setting. All ablations will be guided by intraoperative ultrasound. Ablations will be performed with a 2.45-GHz generator with a 1.8-mm-diameter transcutaneous antenna.

In transarterial bland embolization, beads are delivered directly into the arterial vessels feeding the tumor, usually by a percutaneous coaxial catheter system guided by ultrasound or fluoroscopy through the common femoral artery.

Transarterial embolization

Microwave ablation is a form of thermal ablation used to treat cancer. In this procedure, electromagnetic waves in the microwave energy spectrum (300 MHz to 300 GHz) are applied to tumor tissue. The oscillation of polar molecules produces frictional heating, ultimately generating tissue necrosis within solid tumors.

Microwave Ablation

Dionisios Vrochides, MD PhD

This is a single-center, prospective RCT to study the effectiveness of TACE and MWA combination therapy with MWA monotherapy for the treatment of early HCC. Primary outcome is 2-year intrahepatic disease-free survival.

This single-center, prospective randomized controlled trial (RCT) is designed to compare the outcomes and clinicopathologic results of trans arterial embolization (TAE) and microwave ablation (MWA) combination therapy with MWA monotherapy for the treatment of early (stages 0 and A) hepatocellular carcinoma (HCC). The primary aim of this study is to test the following hypothesis: 2-year intrahepatic disease-free survival does not differ between patients receiving the experimental therapy (MWA + TAE) and patients receiving the standard therapy (MWA alone) as treatment for early stage HCC. Secondary aims are: 1) to determine the clinical feasibility of TAE + MWA in HCC patients with a small tumor burden using patient demographics and disease characteristic data and 2) to determine the effect of TAE on radiographic tumor characteristics in this patient cohort.

The primary outcome is 2-year intrahepatic disease-free survival, which is measured from time of randomization and is defined as the absence of local or regional recurrence of HCC as determined by diagnostic imaging. Local recurrence is defined as an enhancing lesion contiguous with the ablation zone that is present on subsequent imaging but was not present on the initial post-ablation scan. Regional recurrence is defined as hepatic recurrence that is not adjacent to the ablation site.

TAE and MWA Combination Therapy in Early-stage Hepatocellular Carcinoma

Transarterial Embolization and Microwave Ablation Combination Therapy in Early-stage Hepatocellular Carcinoma: A Randomized Trial

Defined as the absence of local or regional recurrence of hepatocellular carcinoma (HCC) as determined by diagnostic imaging

Defined as the absence of local or regional recurrence of hepatocellular carcinoma (HCC) from date of treatment until 2 years after that date as determined by diagnostic imaging

Wake Forest University Health Sciences

In patients randomized to receive the experimental therapy, transarterial embolization (TAE) treatments will be initiated within one week of randomization. Blunt embolization will be performed with LC beads with a maximum size of 700 µm. Microwave ablation (MWA) will be performed up to one month following randomization. The LC beads will be admixed with 8-15 mL of contrast and injected into the arterial branch at a rate of 1-2 mL/min. Treatment may be discontinued if any exclusion criteria develop in the patient or at the patient's request.

Transarterial embolization: In transarterial bland embolization, beads are delivered directly into the arterial vessels feeding the tumor, usually by a percutaneous coaxial catheter system guided by ultrasound or fluoroscopy through the common femoral artery.

Microwave Ablation: Microwave ablation is a form of thermal ablation used to treat cancer. In this procedure, electromagnetic waves in the microwave energy spectrum (300 MHz to 300 GHz) are applied to tumor tissue. The oscillation of polar molecules produces frictional heating, ultimately generating tissue necrosis within solid tumors.

TAE + MWA Combination Therapy

Microwave ablation (MWA) will be performed up to one month following randomization. Treatment may be discontinued if any exclusion criteria develop in the patient or at the patient's request. All operative MWAs will be performed in a laparoscopic or robot-assisted laparoscopic setting. All ablations will be guided by intraoperative ultrasound. Ablations will be performed with a 2.45-GHz generator with a 1.8-mm-diameter transcutaneous antenna.

Microwave Ablation: Microwave ablation is a form of thermal ablation used to treat cancer. In this procedure, electromagnetic waves in the microwave energy spectrum (300 MHz to 300 GHz) are applied to tumor tissue. The oscillation of polar molecules produces frictional heating, ultimately generating tissue necrosis within solid tumors.

MWA Monotherapy

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

United States

Region of Enrollment

Consented Participants

Cirrhosis Present

Ascites Present

History of Hepatic Encephalopathy

History of Ascites

Please Note if any of the following are present (HCV, HPV, Heavy Alcohol use, drug use, nicotine use

Please Note if any previous treatment occured (colon: ablation, tace, chemo, embolization, resection

Please note any previous antiviral therapy the patient has received (IFN, PEG-IFN, Harvon, Other)

Method of diagnosis for HCC - CT

Method of diagnosis for HCC - MRI

Method of diagnosis for HCC - Biospy

Study closed early due to physician decision.

Blair Stephenson, Research Business Manager

The analysis population description is not available. This study was terminated 1 year and 10 months after the enrollment of the first patient. There was not enough funding the support this study, and the PI opted to terminate the study.

Intrahepatic Disease-free Survival

Overall Survival

Intrahepatic Disease-free Survival - 1 Year

Postoperative Morbidity

Postoperative Mortality

Overall Survival - 3 Years

Overall Survival - 5 Year

Intrahepatic Disease-free Survival - 2 Year

Intrahepatic Disease-free Survival - 3 Year

Intrahepatic Disease-free Survival - 5 Year

Overall Study

AFP + GM-CSF Plasmid Prime and AFP Adenoviral Vector Boost

James Pingpank, MD

To evaluate the safety, toxicity and immunological effects of adjuvant administration of an experimental therapy consisting on priming with three intramuscular administrations of a plasmid expressing human AFP (phAFP) together with a plasmid expressing human GM-CSF (phGM-CSF), followed by a single intramuscular boost with an AFP adenoviral vector (AdVhAFP) to patients with locoregionally pre-treated hepatocellular carcinoma (HCC).

Immunization With AFP + GM CSF Plasmid Prime and AFP Adenoviral Vector Boost in Patients With Hepatocellular Carcinoma

A Phase I/II Trial Testing Immunization With AFP + GM CSF Plasmid Prime and AFP Adenoviral Vector Boost in Patients With Hepatocellular Carcinoma

National Cancer Institute (NCI)

Lisa H. Butterfield, Ph.D.

Professor of Medicine, Surgery and Immunology

Antineoplastic Agents

Amino Acids

Nivolumab

Relatlimab

Tyrosine Kinase Inhibitors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Tyrosine

Bristol-Myers Squibb

The purpose of this study is to evaluate the effectiveness and safety of relatlimab in combination with nivolumab in participants with advanced liver cancer who have never been treated with immuno-oncology therapy, after prior treatment with tyrosine kinase inhibitor therapy.

A Study of Relatlimab in Combination With Nivolumab in Participants With Advanced Liver Cancer Who Have Never Been Treated With Immuno-oncology Therapy After Prior Treatment With Tyrosine Kinase Inhibitors

A Phase 2, Randomized, Open-label Study of Relatlimab in Combination With Nivolumab in Participants With Advanced Hepatocellular Carcinoma Who Are Naive to IO Therapy But Progressed on Tyrosine Kinase Inhibitors (RELATIVITY-073)

Pembrolizumab

Chlorotrianisene

Investigational arm: regorafenib at a dose of 90 mg orally once per day (on days 1 to 21 of a 28-day cycle), in combination with pembrolizumab 400 mg using a 30-minute intravenous infusion, on day 1 of a 6-week cycle.

Control arm: Patients will be treated with TACE or TARE "on-demand" according to site's standard of practice.

Randomized patients will receive regorafenib at a dose of 90 mg per day by mouth on days 1 to 21 of a 28-day cycle, in combination with pembrolizumab 400 mg using a 30-minute intravenous infusion, on day 1 (D1) of a 6-week cycle.

Regorafenib in combination with pembrolizumab

Patients will be treated with TACE or TARE "on-demand" according to site's standard of practice.

Loco-regional therapy

Project Management

Peter R Galle, MD

Richard S Finn, MD

REPLACE is a phase III, multicenter, randomized, open-label trial to evaluate the efficacy and safety of regorafenib and pembrolizumab (Rego-Pembro) versus transarterial chemoembolization (TACE) or transarterial radioembolization (TARE) for the first-line treatment of hepatocellular carcinoma (HCC or liver cancer). Approximately 496 patients in around 80 clinical sites worldwide will be randomized to receive either:

* Investigational arm: Regorafenib in combination with pembrolizumab
* Control arm: Transarterial chemoembolization (TACE) or transarterial radioembolization (TARE)

In both arms, patients will receive trial treatment until progressive disease, unacceptable toxicity, deterioration of patient's condition that warrants permanent trial treatment discontinuation or other treatment discontinuation criteria is met. After trial treatment discontinuation, subsequent treatment will be administered according to the Investigator's clinical judgment.

REPLACE is a phase III, multicenter, randomized, open-label trial to evaluate the efficacy and safety of systemic therapy with Rego-Pembro versus loco-regional therapy with TACE or TARE, for the first-line treatment of intermediate-stage HCC with beyond up-to-7 criteria. Approximately 496 patients (\~248 in each arm) from approximately 80 sites will be randomized in order to power the trial efficiently to measure a clinically meaningful improvement for the primary endpoint, PFS according to mRECIST based on the Investigator´s assessment.

The trial will include patients who have been diagnosed with intermediate-stage HCC by biopsy, cytology or diagnostic imaging, such as dynamic computed tomography (CT) or magnetic resonance imaging (MRI), according to the criteria of the American Association for the Study of Liver Diseases (AASLD). Patients should have at least one measurable lesion per RECIST 1.1, disease not amenable to curative treatment but amenable to loco-regional therapy with TACE (cTACE or DEB-TACE) or TARE, ECOG PS 0-1, Child-Pugh class A, and beyond up-to-7 criteria.

The trial will include the following phases:

* Screening
* Treatment
* Follow-up

Randomized patients will receive either:

Investigational arm (Arm A):

-Regorafenib at a dose of 90 mg orally q.d. on days 1 to 21 of a 4-week cycle.

In combination with:

-Pembrolizumab 400 mg using a 30-minutes i.v. infusion, on day 1 (D1) of a 6-week cycle.

Control arm (Arm B):

-Patients will be treated with TACE or TARE "on-demand" according to site's standard, with the goal of controlling all known liver lesions.

In both arms, patients will receive trial treatment (Rego-Pembro or TACE/TARE) until PD per mRECIST, unacceptable toxicity, deterioration of patient's condition that warrants permanent trial treatment discontinuation or other treatment discontinuation criteria are met.

Regorafenib-pembrolizumab vs. TACE/TARE in Intermediate Stage HCC Beyond Up-to-7

A Phase III, Multicenter, Randomized, Open-label Trial to Evaluate the Safety and Efficacy of Systemic Therapy With Regorafenib and Pembrolizumab Versus Locoregional Therapy With Transarterial Chemoembolization or Transarterial Radioembolization, for the First-line Treatment of Intermediate-stage Hepatocellular Carcinoma With Beyond Up-to-7 Criteria

PFS, defined as the time (in months) from the date of randomization until the date of progressive disease (PD) or death due to any cause, whichever occurs first. PD will be assessed locally by the Investigator using mRECIST.

PFS, defined as the time (in months) from the date of randomization until the date of progressive disease (PD) or death due to any cause, whichever occurs first. PD will be assessed locally by the Investigator using RECIST 1.1.

PFS, defined as the time (in months) from the date of randomization until the date of PD or death due to any cause, whichever occurs first. PD will be assessed by BICR using, independently, mRECIST and RECIST 1.1.

OS, defined as the time (in months) from the date of randomization until the date of death due to any cause.

ORR, defined as the proportion of patients who have a complete response (CR) or partial response (PR) according to RECIST v.1.1 and mRECIST, based on the Investigator's and BICR assessment.

To evaluate the two treatment arms (rego-pembro versus loco-regional therapy) with respect to TTUP. TTUP, defined as the time (in months) from the date of randomization until any of the following criteria are met:

* Factors related to liver function:

  * Decompensated cirrhosis (Child-Pugh class B score \> 8), including jaundice, clinical hepatic encephalopathy, and refractory ascites and/or hepatorenal syndrome
  * Impaired portal-vein blood flow (portal-vein thrombus, hepatofugal blood flow)
  * ECOG PS ≥ 2 Note: transient post-TACE/TARE impairment of liver function of Child-Pugh class B score \> 8, that return to pre-TACE/TARE values within 4 weeks of the TACE/TARE session will not qualify as TTUP.
* Factors related to HCC:

  * Failure of the treated nodule to achieve Stable Disease (SD), PR or CR by mRECIST
  * Malignant portal vein thrombosis
  * Marcovascular invasion (MVI) or Extra-hepatic Spread (EHS)

To evaluate the two treatment arms with respect to DOR. DOR, defined as the time (in months) from first documentation of response (PR or CR) to PD or death, based on Investigator's assessment or death from any cause, in patients who had a best overall response of CR or PR.

The NCI-CTCAE is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading scale is provided for each AE term with unique clinical descriptions of severity based on this general guideline: Grade 1 (mild) to 5 (death). AEs will be tabulated by treatment arm, system organ class, preferred term, severity, and relationship to treatment.

To evaluate the patient reported outcomes in the two treatment arms (rego-pembro versus loco-regional therapy) as assessed by EORTC QLQ C30. EORTC QLQ C30 is a quality-of-life questionnaire to assess patients' physical, psychological and social functions. The questionnaire is composed of functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, and nausea and vomiting), global health status and quality of life scale, also several single-item symptom measures (scaling of items: 1 = Not at all to 4 = Very much; 1 = Very poor to 7 = Excellent). Scores range from 0 to 100, with a high score representing a better health-related quality of life.

To evaluate patient reported outcomes in the two treatment arms (rego-pembro versus loco-regional therapy) as assessed by EORTC QLQ-HCC18. EORTC QLQ-HCC18 is an 18-question module specifically to assess symptom burden and impact on health-related quality of life measuring HCC-specific symptoms. The instrument is an 18-item scale, and scores are based on a 4-point Likert scale (with 1 = 'not at all' to 4 = 'very much'); scaled scores range from 0-100 with a higher score indicating worse symptoms.

To evaluate patient reported outcomes for health-related quality of life in the two treatment arms (rego-pembro versus loco-regional therapy) as assessed by health questionnaire EQ-5D-5L. Each dimension (Mobility, Self-care, Usual activities, Pain \& discomfort, Anxiety \& depression) in the EQ-5D-5L has five response levels: no problems (Level 1); slight; moderate; severe; and extreme problems (Level 5). There are 3,125 possible health states defined by combining one level from each dimension, ranging from 11111 (full health) to 55555 (worst health).

Bayer

Translational Research in Oncology

Laparoscopic microwave ablation surgery utilizing the Advanced Image Guidance system for needle placement.

Patients with hepatocellular carcinoma will be treated through laparoscopic microwave ablation surgery, in which the surgeon will utilize a new guidance system for needle placement.

Advanced Image Guidance

David A Iannitti, MD

Advanced Image Guidance for this study was used during laparoscopic microwave ablation surgery to help the surgeon accurately place the ablation needle into the tumor of patients diagnosed with liver cancer.

Hepatocellular carcinoma (HCC) is diagnosed in over 19,000 Americans annually and responsible for 17,000 deaths. Worldwide, (HCC) is the third leading cause of cancer death. Hepatocellular carcinoma recurs frequently due to its multi-centric nature, which requires repeated treatments and often results in progressively fewer treatment options because of severe underlying liver dysfunction. While surgery offers the best prognosis for such tumors and lesions, only 10-15% of all patients are candidates for removal by surgical means, necessitating the exploration of other treatment options. InnerOptic's AIM Guidance System is designed to alleviate the difficulty in using ultrasound to place a needle. AIM shows the needle and the ultrasound slice in their locations in 3D on a stereo monitor, making the spatial relationship between them obvious. AIM also displays the needle trajectory and where the needle will intersect with the ultrasound image, providing the surgeon with an indication of where the needle will go, if inserted along the needle shaft. AIM can also render an ablation volume guide, providing the surgeon with further confirmation that the needle is placed accurately and providing a volumetric guide regarding the power settings of the ablation.

Advanced Image Guidance Utilized in Liver Surgery

Advanced Image Guidance for Ablation Probe Placement in Laparoscopic Liver Surgery: A Pilot Study

Once the ablation antenna has been placed into the target lesion, the success or failure of the attempt will be confirmed with conventional ultrasound alone, in two planes. If the placement is deemed successful, the surgeon will commence the ablation of the tumor. If the placement is deemed insufficient, the probe will be removed and another placement will be attempted using conventional guidance.

A subjective grading scale from which the surgeon will provide the relative ease of lesion targeting using Advanced Image Guidance (AIM) and the guidance system; the scale will be numbered 1-5 with one being significantly difficult and five being significantly easy. The percentage of participants with a score of 5 is reported below.

InnerOptic

Laparoscopic microwave ablation surgery utilizing the Advanced Image Guidance system for needle placement.

Advanced Image Guidance: Patients with hepatocellular carcinoma will be treated through laparoscopic microwave ablation surgery, in which the surgeon will utilize a new guidance system for needle placement.

Intraoperative Imaging

Principal Investigator

Successful Insertion of Ablation Antenna Into Target Lesion

Percentage of Participants With Significant Ease of Lesion Targeting Using Advanced Image Guidance (AIM)

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Respiratory Aspiration

Patients with HCC or metastatic liver lesions who are refered to the abdominal imaging and biopsy clinic will have a liver biopsy performed. 3-5 days after a clinical MRI indicating a cancerous lesion, patients will return for the free-breathing MRI and a liver biopsy. These images will be compared to the clinical MRI and to images of the benign lesions.

Patients with benign liver lesions will be referred to the study team. 3-5 days after a clinical MRI an experimental, free-breathing MRI will be performed on these patients. The results will be compared to their clinical MRI images and to images of HCC or metastatic lesions

patients with HCC or metastatic lesions will have a liver biopsy performed after the experimental MRI. This biopsy will be examined to confirm the imaging results

liver biopsy

All patients will be asked to come in for an MRI scan using techniques developed which minimize the time a patient has to hold their breath to image the liver to \<8 seconds and validate quantifiable techniques which improve liver image quality

free-breathing MRI

Vikas Gulani, MD

The primary objective of this study is to develop and validate simultaneous free-breathing 4D fat and water quantification and quantitative dynamic contrast enhanced perfusion in the liver. Secondary aims include developing and validating free breathing quantification of relaxation parameters T1 and T2, and developing and validating a minimal breath-hold (\< 8 s) high quality diffusion exam using highly accelerated steady state diffusion imaging sequences. Investigators aim to scan 100 subjects receiving liver biopsies as a part of their standard care and another 70 subjects with known benign lesions. The study is greater than minimal risk.

The investigators hypothesize that a quantitative and near free-breathing MRI approach with Hepatocellular carcinoma (HCC) patients will lead to improved tissue characterization, resulting in fewer ambiguous readings and thus fewer biopsies. As each component of the proposed methodology has been experimentally validated in the investigators preliminary work, the next appropriate step would be to evaluate the clinical feasibility of the exam. The investigators goal is to test the ability of quantitative MRI techniques to provide high quality images of the liver and to differentiate liver lesions from one another in a time frame shorter than a current clinical exam.

Assessment of Novel MRI Quantification Free Breathing Technique in Evaluation of Liver Lesions

Dynamic Contrast Enhanced MRI data were used to calculate three quantitative perfusion properties using a dual input, single tissue compartment model of gadolinium based contrast agents in the liver in HCC, metastatic, and benign lesions.

One of these quantitative perfusion properties is Mean Arterial fraction, which is the proportion of blood flow derived from hepatic artery.

Dynamic Contrast Enhanced MRI data were used to calculate three quantitative perfusion properties using a dual input, single tissue compartment model of gadolinium based contrast agents in the liver in HCC, metastatic, and benign lesions.

One of these quantitative perfusion properties is DV. DV corresponds to the volume of extracellular, extravascular space in a tissue which is a measure of the tissue cellularity

Dynamic Contrast Enhanced MRI data were used to calculate three quantitative perfusion properties using a dual input, single tissue compartment model of gadolinium based contrast agents in the liver in HCC, metastatic, and benign lesions.

One of these quantitative perfusion properties is MTT. MTT corresponds to the average time, in seconds, that red blood cells spend within a determinate volume of capillary circulation

Quantified and validated relaxation parameters when creating T1 (spin-lattice) and T2 (spin-spin) weighted images

The minimum time (in seconds) a patient must hold their breath to produce quality liver images during an MRI. Developing and validating a minimal breath-hold (\< 8 s) high quality diffusion exam using highly accelerated steady state diffusion imaging sequences.

Case Comprehensive Cancer Center

Patients with HCC or metastatic liver lesions who are refered to the abdominal imaging and biopsy clinic will have a liver biopsy performed. 3-5 days after a clinical MRI indicating a cancerous lesion, patients will return for the free-breathing MRI and a liver biopsy. These images will be compared to the clinical MRI and to images of the benign lesions.

liver biopsy: patients with HCC or metastatic lesions will have a liver biopsy performed after the experimental MRI. This biopsy will be examined to confirm the imaging results free-breathing MRI: All patients will be asked to come in for an MRI scan using techniques developed which minimize the time a patient has to hold their breath to image the liver to \<8 seconds and validate quantifiable techniques which improve liver image quality

Dynamic Contrast Enhanced MRI

Patients with benign liver lesions will be referred to the study team. 3-5 days after a clinical MRI an experimental, free-breathing MRI will be performed on these patients. The results will be compared to their clinical MRI images and to images of HCC or metastatic lesions free-breathing MRI: All patients will be asked to come in for an MRI scan using techniques developed which minimize the time a patient has to hold their breath to image the liver to \<8 seconds and validate quantifiable techniques which improve liver image quality

Free-Breathing Quantification of Relaxation Parameters

Patients with HCC or metastatic liver lesions who are refered to the abdominal imaging and biopsy clinic will have a liver biopsy performed. 3-5 days after a clinical MRI indicating a cancerous lesion, patients will return for the free-breathing MRI and a liver biopsy. These images will be compared to the clinical MRI and to images of the benign lesions.

liver biopsy: patients with HCC or metastatic lesions will have a liver biopsy performed after the experimental MRI. This biopsy will be examined to confirm the imaging results

free-breathing MRI: All patients will be asked to come in for an MRI scan using techniques developed which minimize the time a patient has to hold their breath to image the liver to \<8 seconds and validate quantifiable techniques which improve liver image quality

Patients with benign liver lesions will be referred to the study team. 3-5 days after a clinical MRI an experimental, free-breathing MRI will be performed on these patients. The results will be compared to their clinical MRI images and to images of HCC or metastatic lesions

free-breathing MRI: All patients will be asked to come in for an MRI scan using techniques developed which minimize the time a patient has to hold their breath to image the liver to \<8 seconds and validate quantifiable techniques which improve liver image quality

Age, Categorical

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Metastatic Cancer

Benign

No confirmed diagnosis, other malignant, or no visible lesion/path

Lesion type

Free breathing quantification of T1 and T2 was explored and initial tests were run as part of this study. However, free-breathing acquisition of data yielded substantial image blurring, making it impossible to accurately delineate and characterize lesions. Several technical improvements were implemented, but improved image quality was not achieved. Dynamic Contrast Enhanced MRI data from this study combined with data from a second institution were published in Nature Scientific Reports in 2018

Dr. Vikas Gulani

Dynamic Contrast Enhanced MRI - HCC Lesions

Dynamic Contrast Enhanced MRI - Metastatic Lesions

Dynamic Contrast Enhanced MRI - Benign Lesions

Evaluable participants (those who completed study with applicable lesions). Note - There were only sufficient number of participants to statistically compare HCC and Metastatic lesion groups due to the low number of benign lesions. No data are available for the "Free-breathing Quantification of Relaxation Parameters" for reasons listed in participant flow section - primarily relating to image blurring and artifacts.

Arterial Fraction

Quality of images were poor and could not be used for analysis

Free Breathing Quantification of Relaxation Parameters

Although the study team worked on the development of this technology as part of an NIH grant, this technology was not utilized as a part of this study so no data were collected.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Intravenous TKM-080301 in Subjects With Advanced Hepatocellular Carcinoma	NCT02191878	Hepatocellular ... Hepatoma Liver Cancer, A... Liver Cell Carc...	TKM-080301	18 Years -	Arbutus Biopharma Corporation
TAE and MWA Combination Therapy in Early-stage Hepatocellular Carcinoma	NCT02704130	Hepatocellular ... Hepatoma Liver Cancer, A... Liver Cell Carc... Liver Cell Carc...	Transarterial e... Microwave Ablat...	18 Years - 75 Years	Wake Forest University Health Sciences
Immunization With AFP + GM CSF Plasmid Prime and AFP Adenoviral Vector Boost in Patients With Hepatocellular Carcinoma	NCT00669136	Hepatocellular ... Hepatoma Liver Cancer, A... Liver Cell Carc... Liver Cell Carc... Cancer of Liver Cancer of the L... Cancer, Hepatoc... Hepatic Cancer Hepatic Neoplas... Hepatocellular ... Liver Cancer Neoplasms, Hepa... Neoplasms, Live...	AFP + GM-CSF Pl...	18 Years - 80 Years	University of Pittsburgh
Immunization With AFP + GM CSF Plasmid Prime and AFP Adenoviral Vector Boost in Patients With Hepatocellular Carcinoma	NCT00669136	Hepatocellular ... Hepatoma Liver Cancer, A... Liver Cell Carc... Liver Cell Carc... Cancer of Liver Cancer of the L... Cancer, Hepatoc... Hepatic Cancer Hepatic Neoplas... Hepatocellular ... Liver Cancer Neoplasms, Hepa... Neoplasms, Live...	AFP + GM-CSF Pl...	18 Years - 80 Years	University of Pittsburgh
A Study of Relatlimab in Combination With Nivolumab in Participants With Advanced Liver Cancer Who Have Never Been Treated With Immuno-oncology Therapy After Prior Treatment With Tyrosine Kinase Inhibitors	NCT04567615	Hepatocellular ... Hepatoma Liver Cancer, A... Liver Cell Carc... Liver Cell Carc...	Nivolumab Relatlimab	18 Years -	Bristol-Myers Squibb
Regorafenib-pembrolizumab vs. TACE/TARE in Intermediate Stage HCC Beyond Up-to-7	NCT04777851	Carcinoma, Hepa...	Regorafenib in ... Loco-regional t...	18 Years -	Translational Research in Oncology
Advanced Image Guidance Utilized in Liver Surgery	NCT01666145	Carcinoma, Hepa...	Advanced Image ...	18 Years -	Wake Forest University Health Sciences
Assessment of Novel MRI Quantification Free Breathing Technique in Evaluation of Liver Lesions	NCT02095678	Hepatocellular ...	liver biopsy free-breathing ...	18 Years - 100 Years	Case Comprehensive Cancer Center

Spots Global Cancer Trial Database for liver cell carcinoma, adult