EXALT: EXercise Attenuates Liver Tumors Trial (EXALT)

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.

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Behavioral: Exercise intervention

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise intervention; 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; 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.
No Intervention: Standard of Care; Subjects are instructed to maintain their current activity level.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2019
• Primary Completion (Actual): September 9, 2021
• Study Completion (Actual): September 9, 2021

Study Registration Dates

• First Submitted: May 31, 2019
• First Submitted That Met QC Criteria: June 5, 2019
• First Posted (Actual): June 7, 2019

Study Record Updates

• Last Update Posted (Actual): March 9, 2022
• Last Update Submitted That Met QC Criteria: February 21, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: liver cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Carcinoma, Hepatocellular; Liver Neoplasms
• Other Study ID Numbers: STUDY00012527

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No