PICaSO-ES: Prehabilitation to Improve Cancer Surgery Outcomes in AYA Patients With Extremity Sarcomas

Sponsor

University Health Network, Toronto (Other)

Overall Status

Suspended

CT.gov ID

NCT04248959

Collaborator

MOUNT SINAI HOSPITAL (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the feasibility of a multimodal prehabilitation intervention intended to optimize postoperative recovery in adolescents and young adults (AYAs) diagnosed with soft tissue and bone-based sarcomas of the upper and lower extremities (extremity sarcomas; ES).

Condition or Disease	Intervention/Treatment	Phase
Sarcoma,Soft Tissue Osteosarcoma	Behavioral: Multimodal prehabilitation	N/A

Detailed Description

Objectives:

The objective of the study is to determine if a larger investigation of HIIT-based multimodal prehabilitation is feasible in AYA patients awaiting major ES surgery. Specific aims of the study are:

To determine the feasibility of conducting a larger phase II investigation of HIIT-based multimodal prehabilitation according to three primary criteria, including (i) recruiting

=50% of otherwise eligible patients (OEP; i.e., patients meeting all eligibility criteria), (ii) no patient experiences a testing-related or an intervention-related serious adverse event (SAE), and (iii) patients achieve an exercise intervention adherence rate of >=70%.

To further determine the feasibility of conducting a larger phase II investigation of HIIT-based multimodal prehabilitation according to the secondary feasibility criteria.
To explore the effect of prehabilitation on global health score, preoperative cardiorespiratory fitness, physical function, short-term perioperative outcomes, and patient-reported outcomes (e.g., symptom burden and health-care utilization).

Methods:

This pilot study is a phase I, two-arm randomized control trial to assess the feasibility of high-intensity interval training-based multimodal prehabilitation in newly diagnosed AYAs with ES.

Patients will be randomized to either the prehabilitation group or the usual care group.

Patients in the prehabilitation group will be prescribed both physical and psychological prehabilitation prior to undergoing major extremity sarcoma surgery (described below).

The usual care group will be counseled to continue their current level of activity and given the information on exercise as outlined in the Cancer Care Ontario guidelines. Patients in the usual care group will also be given the same physical activity trackers and weekly exercise tracking logs as the patients in the prehabilitation group to eliminate the effect of activity tracking as an intervention itself and to facilitate descriptive comparisons of physical activity engagement between the groups.

Feasibility (e.g., recruitment, safety, tolerability), clinical, fitness, patient-reported outcomes and health system utilization outcomes will be evaluated. Outcomes will be measured at baseline (T0), immediately preoperatively (T1), and postoperatively at one (T2), three (T3) and six (T4) months.

Feasibility data will be collected via logs completed by the research coordinators (during recruitment and postoperative follow-up) and by the study lead / research assistants (during the intervention period in person (during each supervised exercise session) and via weekly patient phone calls (usual care group only)).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

Prehabilitation to Improve Cancer Surgery Outcomes in AYA Patients With Extremity Sarcomas (PICaSO-ES): A Pilot Randomized Controlled Trial

Anticipated Study Start Date :

Apr 1, 2021

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PREHAB Facility and home-based multimodal prehabilitation (aerobic exercise training, resistance exercise training, mindfulness)	Behavioral: Multimodal prehabilitation Physical Prehabilitation: Combination facility-/home-based exercise consisting of aerobic exercise (4-5 days/week (d/wk)), resistance exercise (2-3 d/wk), and daily mindfulness practice. Aerobic exercise Facility-based, high-intensity interval training (HIIT), 2 d/wk, 35 min/session, 4-min work and 3-min recovery period; cycle ergometer or arm ergometer (for those who cannot weight-bear) at 75% to 95% of baseline VO2peak Home-based, moderate-intensity continuous training (MICT), 2-3 d/wk, >=30 min/session, brisk walking (or equivalent) aiming to achieve a target HR of 40-70% of maximal HR Resistance exercise Home-based, moderate-intensity resistance training, 2-3 d/wk, all major muscle groups (working around tumour-related deficits), 8-10 exercises, 12-15 repetitions, resistance bands and body weight based Psychological Prehabilitation: Daily mindfulness practice, 20 min/session, and guided by audio file created at Mount Sinai Hospital
No Intervention: USUAL CARE Self-directed physical activity and provision of Cancer Care Ontario's physical activity guidelines for cancer survivors

Arm

Intervention/Treatment

Experimental: PREHAB

Facility and home-based multimodal prehabilitation (aerobic exercise training, resistance exercise training, mindfulness)

Behavioral: Multimodal prehabilitation

Physical Prehabilitation: Combination facility-/home-based exercise consisting of aerobic exercise (4-5 days/week (d/wk)), resistance exercise (2-3 d/wk), and daily mindfulness practice. Aerobic exercise Facility-based, high-intensity interval training (HIIT), 2 d/wk, 35 min/session, 4-min work and 3-min recovery period; cycle ergometer or arm ergometer (for those who cannot weight-bear) at 75% to 95% of baseline VO2peak Home-based, moderate-intensity continuous training (MICT), 2-3 d/wk, >=30 min/session, brisk walking (or equivalent) aiming to achieve a target HR of 40-70% of maximal HR Resistance exercise Home-based, moderate-intensity resistance training, 2-3 d/wk, all major muscle groups (working around tumour-related deficits), 8-10 exercises, 12-15 repetitions, resistance bands and body weight based Psychological Prehabilitation: Daily mindfulness practice, 20 min/session, and guided by audio file created at Mount Sinai Hospital

No Intervention: USUAL CARE

Self-directed physical activity and provision of Cancer Care Ontario's physical activity guidelines for cancer survivors

Outcome Measures

Primary Outcome Measures

Patient recruitment rate (feasibility target: >=50% of eligible participants) [Initiation through end of study recruitment at 12 months]
Defined as the percent of consenting patients based on the total number of otherwise eligible patients (OEP; patients meeting all study eligibility criteria) approached
Testing- and intervention-related serious adverse events (feasibility target: none) [Initiation through end of pre-operative testing at a maximum of 6 months post-randomization]
Defined as the number and frequency of testing- and intervention-related serious adverse events (SAEs) according to the Common Terminology Criteria for Adverse Events
Patient exercise adherence (feasibility target: >=70% of prescribed) [Initiation through end of study intervention period at a maximum of 6 months post-randomization]
Defined as relative dose intensity as the percent of total dose of exercise performed relative to the total planned dose prescribed and quantified according to metabolic equivalents

Secondary Outcome Measures

Patient identification rate (feasibility target: >=50% of OEP) [Initiation through end of study recruitmentat 12 months]
Defined as the average number of OEP identified each month
Baseline assessment rate (feasibility target: >=90% of consenting participants) [Initiation through end of study recruitment at 12 months]
Defined as the percent of consenting patients who successfully complete baseline assessments based on the total number of consenting patients
Intervention window (feasibility target: >=21 days) [Initiation through end of study intervention period at a maximum of 6 months post-randomization]
Defined as the average elapsed time (in days) between diagnosis and extremity sarcoma surgery
Testing- and intervention-related non-serious adverse events (feasibility target: <20% of sessions) [Initiation through end of pre-operative testing at a maximum of 6 months post-randomization]
Defined as the number and frequency of testing- and intervention-related non-serious adverse events (nSAEs) according to the Common Terminology Criteria for Adverse Events
Testing performance (feasibility target: >=95% completion of tests) [Initiation through end of pre-operative testing at a maximum of 6 months post-randomization]
Defined as percent completion of all VO2peak and 6-minute walk tests at baseline and follow-up
Testing modality adaptations (descriptive) [Initiation through end of pre-operative testing at a maximum of 6 months post-randomization]
Defined as the percent of all tests which are adapted for functional or safety reasons
Training modality adaptations (descriptive) [Initiation through end of study intervention period at a maximum of 6 months post-randomization]
Defined as the percent of all exercise sessions which are adapted for functional or safety reasons
Permanent treatment discontinuation (feasibility target: <=15% of participants) [Initiation through end of study intervention period at a maximum of 6 months post-randomization]
Defined as the percent of patients who discontinue intervention participation prior to the planned end of the intervention period
Treatment interruption (feasibility target: <=15% of participants) [Initiation through end of study intervention period at a maximum of 6 months post-randomization]
Defined as the percent of patients who miss ≥3 consecutive sessions within the intervention period
Dose modification (feasibility target: <=25% of participants) [Initiation through end of study intervention period at a maximum of 6 months post-randomization]
Defined as the percent of exercise sessions requiring a dose reduction during training (i.e., intensity or duration) relative to the total number of sessions completed. Total number of exercise sessions with a reduction in intensity or a reduction in duration will be combined into the numerator when calculating the percentage of affected sessions.
Early session termination (feasibility target: <=25% of participants) [Initiation through end of study intervention period at a maximum of 6 months post-randomization]
Defined as the percent of exercise sessions requiring unplanned early termination
Pretreatment intensity modification (feasibility target: <=25% of participants) [Initiation through end of study intervention period]
Defined as the percent of sessions which required pre-exercise modification of the target exercise intensity due to a pre-exercise screening indication (e.g., fatigue, pain)
Physical prehabilitation compliance (feasibility target: >=70% of prescribed) [Initiation through end of study intervention period at a maximum of 6 months post-randomization]
Defined as the percent of exercise sessions completed based on the total number of sessions prescribed
Mindfulness prehabilitation compliance (feasibility target: >=70% of prescribed) [Initiation through end of study intervention period at a maximum of 6 months post-randomization]
Defined as the percent of psychological sessions completed based on the total number of sessions prescribed
Attrition (feasibility target: <=20% loss to follow-up) [Study initiation through end of 6 month post-operative period]
Defined as the percent loss to follow-up (not completing follow-up assessments) for the PREHAB and UC groups, individually and overall

Other Outcome Measures

Global health score [Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3), 6 months postoperative (T4)]
Primary exploratory outcome: European Organization for the Research and Treatment of Cancer (EORTC) QLC-C30
Postoperative complications [1 month postoperative (T2), 3 months postoperative (T3)]
Postoperative complication severity and frequency defined according to the Common Terminology Criteria for Adverse Events.
Length of stay [1 month postoperative (T2)]
Average postoperative hospitalization period
Peak cardiorespiratory fitness (VO2peak) [Baseline (T0), preoperative (T1)]
Cardiopulmonary exercise test (CPET)-based assessment of VO2peak
Post-exercise heart rate recovery [Baseline (T0), preoperative (T1)]
Heart rate difference between the immediate end of CPET, 1 minute and 2 minutes recovery
Functional capacity [Baseline (T0), preoperative (T1)]
Total distance traveled during six-minute walk test
Physical activity behavior (subjective) [Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3)]
Godin Leisure-time Exercise Questionnaire
Physical activity behavior (objective) [Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3)]
Lynk2 physical activity tracking device (average steps per day)
Health-related quality of life [Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3), 6 months postoperative (T4)]
EQ-5D; All 5 items are rated on a 1 to 3 scale with higher numbers reflecting worse outcomes.
Symptom burden [Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3), 6 months postoperative (T4)]
Edmonton Symptom Assessment Scale (ESAS); All 10 items are rated on a 0 to 10 scale with higher numbers reflecting worse outcomes.
Anxiety and depression [Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3), 6 months postoperative (T4)]
Hospital Anxiety and Depression Scale (HADS); All 14 items are rated on a 0 to 3 scale with higher numbers reflecting worse outcomes.
Fatigue [Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3), 6 months postoperative (T4)]
Functional Assessment of Chronic Illness Therapy-Fatigue scale (FACIT-F); All 13 items are rated on a 0 to 4 scale with higher numbers reflecting worse outcomes.
Impact on work [Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3), 6 months postoperative (T4)]
Work Limitations Questionnaire
Social support [Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3), 6 months postoperative (T4)]
Medical Outcomes Study Social Support Scale (SF-20); All item scores transformed into 0 to 100 scales with higher scores reflecting better outcomes.
Relationships [Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3), 6 months postoperative (T4)]
Experiences in Close Relationships scale (ECR); All 36 items rated on a 1 to 7 scale with higher scores reflecting worse outcomes.
Extremity function [Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3), 6 months postoperative (T4)]
Toronto Extremity Salvage Score (upper or lower)
Disease burden [Baseline (T0), preoperative (T1), 1 month postoperative (T2), 3 months postoperative (T3), 6 months postoperative (T4)]
Musculoskeletal Tumor Society score
Health care utilization [Baseline (T0), 1 month postoperative (T2), 3 months postoperative (T3), 6 months postoperative (T4)]
Health Service Utilization Inventory

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 39 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

≥18 years and <40 years of age at diagnosis
Fluent in English
Able to comply with study and follow-up procedures contained within the consent form
Pathologically or radiologically confirmed diagnosis of a soft-tissue or osteosarcoma of the upper or lower extremities
Soft-tissue or osteosarcoma must be considered operable
Patients of all weight bearing states will be eligible
Expected LOS ≥ 5 days as calculated by the validated American College of Surgeons Surgical Risk Calculator
14 days between time of randomization and time of expected surgery
Patient written, informed consent obtained according to ICH GCP guidelines and local regulations
Medical clearance to participate in the study from either the primary treating surgeon (JW, PF) or oncologist (AG)

Exclusion Criteria:

Planned resection of bony pelvis or major lower extremity neurovascular structures
Significant comorbidity including any of the following:
Canadian Cardiovascular Society class III/IV coronary disease
New York Heart Association class III/IV congestive heart failure
Neurologic or musculoskeletal disorder prohibiting exercise
Major neuropsychiatric disorder
High-risk or presence of pathological fracture