Multimodal Prehabilitation During Chemotherapy in Patients With Colorectal Liver Metastases (PREHABMET)

Multimodal Prehabilitation During Neoadjuvant Chemotherapy in Patients With Colorectal Liver Metastases: a Randomized Controlled Trial

Liver resection is the only curative treatment for patients with colorectal liver metastases (CRLM). Most patients undergo chemotherapy (CT) before liver surgery. CT objectively decreases patient functional capacity. It has already been demonstrated that a structured training program carried out during the 4 weeks following CT, while the patient is waiting for liver resection, is able to return the functional capacity to baseline levels. Despite this, multimodal prehabilitation programs (MPP) during preoperative CT have not been evaluated or implemented.

The aim of this study is to investigate whether a 16-week MPP applied during and following CT in CRLM patients will result in a significant increase in physical fitness when compared to those that undergo MPP only during the 4-weeks, between the end of CT and liver resection.

Study Overview

• Status: Not yet recruiting
• Conditions: Neoadjuvant Therapy; Liver Metastases; Prehabilitation
• Intervention / Treatment: Behavioral: Physical Prehabilitation

Detailed Description

The primary aim of the study is to evaluate the effectiveness of a multimodal prehabilitation program (MPP) in CRLM patients, which will be implemented right through the period of preoperative CT and during the 4-weeks of recovery before liver resection.

MPP will consist of in-hospital high-moderate intensive exercise training, nutritional assessment and high-protein supplementation, smoking cessation, psychological support and Comprehensive Geriatric Assessment.

Expected improvement in physical fitness will be measured by the difference in meters achieved in the six-minute walk test (6MWT) and will be compared with patients that will follow the MPP only during the 4-weeks before surgery, when preoperative CT has been finished.

Secondary aims include patient reported outcomes measures such as quality of life, postoperative complications, length of hospital stay, 30-day mortality and re-admissions. Protocol feasibility will be evaluated by monitoring all interventions.

• Study Type: Interventional
• Enrollment (Anticipated): 84
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laia Estalella, PhD; Phone Number: +34 628164461; Email: laiaestalella2@gmail.com

Study Locations

• Spain
  • Tarragona, Spain, 43005
    • Hospital Universitari de Tarragona Joan XXIII
    • Contact: Laia Estalella, PhD; Phone Number: +34 628164461; Email: laiaestalella2@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years
• Written informed consent obtained from subject to participate in the study.

Exclusion Criteria:

• Age <18 years
• ASA health class status IV-V
• Mental conditions or disabling orthopedic and neuromuscular disease that prevent physical exercise or may compromise adherence to the program
• Medical contraindication to perform exercise
• Inability to obtain informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 16W group; Multimodal prehabilitation program (MPP) will be implemented during 16 weeks, 12 weeks during chemotherapy (CT) and 4 weeks while waiting for surgery.	Behavioral: Physical Prehabilitation; The prehabilitation program consists of the following interventions: in-hospital high-moderate intensive exercise training, nutritional assessment and high-protein supplementation, smoking cessation, psychological support and Comprehensive Geriatric Assessment.; Other Names: Nutritional intervention; Psychological intervention; Smoking cessation; Comprehensive Geriatric Assessment (CGA) and co-morbidity assessment
Active Comparator: 4W group; Multimodal prehabilitation program (MPP) will start at the end of preoperative chemotherapy (CT) until surgery (4 weeks in total).	Behavioral: Physical Prehabilitation; The prehabilitation program consists of the following interventions: in-hospital high-moderate intensive exercise training, nutritional assessment and high-protein supplementation, smoking cessation, psychological support and Comprehensive Geriatric Assessment.; Other Names: Nutritional intervention; Psychological intervention; Smoking cessation; Comprehensive Geriatric Assessment (CGA) and co-morbidity assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical Fitness- 6MWT	Change in physical fitness will be measured by the six-minute walk test (6MWT). This test measures the distance an individual can walk, in metres, in a 6-minute period. Greater distance walked during the 6MWT indicates greater functional capacity.	Baseline (before chemotherapy), week 12 (end of chemotherapy), week 16 (before surgery), 4 weeks postoperative, 8 weeks postoperative, 1 year postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative complications- Clavien-Dindo classification	The Clavien-Dindo classification consists of 7 grades. Grade I: any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, and radiological interventions; Grade II: Requiring pharmacological treatment with drugs other than such allowed for grade I complications; Grade III (IIIa, IIIb): Requiring surgical, endoscopic or radiological intervention; Grade IV (Iva, IVb): Life-threatening complication requiring IC/ICU management; Grade V: death of the patient.	Through study completion, up to one year postoperative
Postoperative complications- CCI	The Comprehensive Complication Index (CCI) integrates in a single formula all complications by severity, ranging from 0 (uneventful course) to 100 (death).	Through study completion, up to one year postoperative
Postoperative hospital length of stay	The patient's postoperative length of stay will be recorded from the medical records. It will be calculated from the date of surgery until to the date of discharge from the hospital. It will be reported in days.	Postoperative period: assessed up to the first year postoperative
Readmissions rate	Rate of un-planned hospital readmissions within 30 days of discharge after hospitalization.	Postoperative period: Up to 30 postoperative days
Functional capacity- 30CST	The 30-second sit to stand test (30CST) measures lower body strength by recording the maximum number of times an individual can go from a seated position to a standing position, without using their arms, in a 30-second period.	Baseline (before chemotherapy), week 12 (end of chemotherapy), week 16 (before surgery), 4 weeks postoperative, 8 weeks postoperative, 1 year postoperative
Health-related quality of life- SF-36	Quality of life will be evaluated by using the SF-36 mental health score. This survey measures eight scales of health: physical function, role physical, role emotional, social functioning, bodily pain, general health, vitality, and mental health. Each items are scored on a 0 to 100 range. A high score defines a more favorable health state.	Baseline (before chemotherapy), week 16 (before surgery), 8 weeks postoperative, 1 year postoperative
Psychological health- HADS	Emotional health will be measured using the Hospital Anxiety and Depression Scale (HADS). The HADS contains seven items, each scored from 0 to 3 points for anxiety and depression. It provides summary measures on a scale of 0-21, with scores exceeding 8 suggesting the presence of a mood disorder	Baseline (before chemotherapy), week 16 (before surgery), 8 weeks postoperative, 1 year postoperative
Functional capacity- Handgrip strength	It will be measured using an hydraulic hand dynamometer. Three measures from each hand will be taken, with patient seated and arm bent at a 90-degree angle. The average of the three measures for each hand will be recorded.	Baseline (before chemotherapy), week 12 (end of chemotherapy), week 16 (before surgery), 4 weeks postoperative, 8 weeks postoperative, 1 year postoperative
Nutritional status- PG-SGA	The Patient-Generated Subjective Global Assessment (PG-SGA) is a validated questionnaire used to assess the nutritional and functional status of cancer patients. The scoring system allows patients at risk for malnutrition to be identified and triaged for nutritional intervention. A score ≥9 indicates a critical need for nutritional intervention.	Baseline (before chemotherapy), week 12 (end of chemotherapy), week 16 (before surgery), 4 weeks postoperative, 8 weeks postoperative, 1 year postoperative
Nutritional status- BMI	Body Mass Index (BMI) is weight in kilograms divided by height in meters squared.	Baseline (before chemotherapy), week 12 (end of chemotherapy), week 16 (before surgery), 4 weeks postoperative, 8 weeks postoperative, 1 year postoperative
Nutritional status- BIA	The Bio-electrical Impedance Analysis (BIA) is a method to determine body composition. The measurement of body fat in relation to lean body mass.	Baseline (before chemotherapy), week 12 (end of chemotherapy), week 16 (before surgery), 4 weeks postoperative, 8 weeks postoperative, 1 year postoperative
Nutritional status- UMA	Upper-arm muscle area (UMA) is the circumference of the left upper arm, measured at the mid-point between the tip of the shoulder and the tip of the elbow.	Baseline (before chemotherapy), week 12 (end of chemotherapy), week 16 (before surgery), 4 weeks postoperative, 8 weeks postoperative, 1 year postoperative

Collaborators and Investigators

• Sponsor: Institut Investigacio Sanitaria Pere Virgili
• Investigators: Principal Investigator: Laia Estalella, PhD, Hospital Universitari de Tarragona Joan XXIII

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: August 11, 2020
• First Submitted That Met QC Criteria: August 18, 2020
• First Posted (Actual): August 20, 2020

Study Record Updates

• Last Update Posted (Actual): August 20, 2020
• Last Update Submitted That Met QC Criteria: August 18, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Neoplastic Processes; Neoplasm Metastasis; Liver Neoplasms
• Other Study ID Numbers: PREHABMET

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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