EXALT: EXercise Attenuates Liver Tumors Trial

Study Overview
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Brief Summary
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The overall goal of this proposal is to test the effect of exercise to delay or avert HCC recurrence and gain information regarding the potential molecular mechanisms of HCC tumor inhibition by exercise.

Detailed Description
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Primary liver cancer is the leading cause of cancer worldwide. The majority of primary liver cancers are hepatocellular carcinoma (HCC) and occur in the setting of cirrhosis of the liver. Body fat and systemic inflammation are determinants of HCC risk. Cirrhotic patients with HCC are often treated with locoregional therapies including transarterial chemoembolization (TACE) as a bridge to liver transplantation. Despite this, HCC recurrence rates approach 80%. There is a growing body of evidence to suggest the benefit of exercise in cancer patients. Exercise decreases disease recurrence and improves survival in other primary cancers by altering tumor biology and influencing response to treatment. Although animal models suggest biologic plausibility, whether or not exercise prevents HCC recurrence in cancer patients remains unknown. The overall goal of this proposal is to test the effect of exercise to delay or avert HCC recurrence and gain information regarding the potential molecular mechanisms of HCC tumor inhibition by exercise.

Official Title
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EXALT: EXercise Attenuates Liver Tumors Trial

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Behavioral: Exercise intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults age >=18 or <70 years Liver transplant candidates (under evaluation or listed for transplant with HCC) Hepatocellular Carcinoma diagnosis (HCC) Complete response to LRT Exclusion Criteria: Active cardiac symptoms BMI <18 or >45 kg/m2(16) CPT Class B or C liver disease ECOG >2 Hepatic decompensation Institutionalized/prisoner Pregnancy Severe medical comorbidities/psychiatric illness

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: perform an interventional pilot trial and randomize 21 subjects who have had a complete response to TACE to a 3-month exercise intervention (n=14) versus standard of care (n=7) where subjects are instructed to maintain their current activity level.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise intervention<br>The exercise program will be similar to the Exercise in All ChemoTherapy (ENACT) study which combines in-person and home-based strength training and aerobic exercise five days a week. | Behavioral: Exercise intervention<br>* Moving Through Cancer: A Guide to Exercise for Cancer Survivors will serve as the framework for an American College of Sports Medicine certified exercise physiologist with additional Cancer Exercise training to teach proper warm up, use of equipment, exercise form, mode of activity, intensity of exercise, flexibility exercises, and cool down.<br>|
| No Intervention: Standard of Care<br>Subjects are instructed to maintain their current activity level. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility-number of participants able to complete the trial | Defined as completing >80% of the sessions.(46, 47) While this would be expected for patients with cirrhosis,(46) this would be five-fold larger than the proportion of oncology patients receiving systemic treatment who complete other exercise based randomized controlled trials. We expect exercise in subjects with HCC in the background of Child Pugh Turcotte (CPT) Class A cirrhosis without hepatic decompensation (e.g., ascites, hepatic encephalopathy, bleeding gastroesophageal varices) and Eastern Cooperative Oncology Group (ECOG) 0-2 functional status to be feasible. | up to 52 weeks | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Data from previous oncology trials suggest up to 25% of the participants may experience a mild musculoskeletal impairment and zero adverse effects requiring treatment alterations. Pilot exercise-based trials in patients with cirrhosis have demonstrated <5% adverse events. | up to 52 weeks | 
| Acceptability-scientifically adequate | To assess the effectiveness of exercise trials in patients with HCC. The work with the ongoing NASHFit and completed ENACT Trials and the work of others performing exercise-based trials in patients with cirrhosis(50) has established >50% enrollment of subjects approached as a threshold of acceptability. | up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HCC recurrence |  | 3- and 6- month | 
| Overall survival |  | 3- and 6- month | 
| Cancer-free survival |  | 3- and 6- month | 
| waiting-list mortality |  | 3- and 6- month | 
| concentration of IL-6 |  | 3- and 6-month | 
| visceral adipose tissue (VAT) | change in body composition | 3- and 6-month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver cancer