SOPHIE Trial: Surgery in Ovarian Cancer With PreHabilitation In ERAS

Study Overview
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Brief Summary
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The treatment of choice in advanced ovarian cancer is a cytoreductive surgery combined with chemotherapeutic treatment. This complex and aggressive surgery is associated with high postoperative complication rates that may result in a strong negative impact on the clinical results due to the delay with the start of adjuvant chemotherapy as well as the costs from the surgical process. Multimodal prehabilitation has emerged as an innovative intervention that focuses on optimizing physiological and psychological resilience to withstand the upcoming stress of surgery. It has been shown to reduce postoperative complications in major abdominal surgery, but has not been assessed yet in abdominal onco-gynecological surgery.

Detailed Description
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Main objective: To determine the efficacy of multimodal prehabilitation in decreasing postoperative complications in patients undergoing gynecological cancer surgery of high complexity by laparotomy (primary cytoreductive surgery, interval surgery and secondary cytoreductive surgery in advanced ovarian cancer). Design: Multicenter randomized controlled clinical trial. Subjects: 146 patients: 73 in the intervention group and 73 in the control group. Intervention group: PreHAB intervention consists on: High-intensity endurance exercise training program and physical activity promotion remotely controlled with ICT (information and communications technologies). Nutritional counselling to achieve protein intake of 1.5-1.8 g/kg and whey protein supplements. Psychological coping. Control group will receive standard preoperative care. Both groups will receive perioperative care in accordance with the enhanced recovery after surgery (ERAS) guidelines. Measures: Aerobic capacity (incremental stress test), physical activity, operative complications and hospital length and associated costs.

Official Title
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SOPHIE: Surgery in Ovarian Cancer With PreHabilitation In ERAS: Prospective Multicentre Study

Conditions
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Advanced Ovarian Cancer

Intervention / Treatment
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* Other: Multimodal Prehabilitation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with advanced ovarian cancer subject to primary debulking surgery or interval surgery after 3-4 cycles of chemotherapy or secondary and / or tertiary debulking surgery . Patients with Eastern Cooperative Oncology Group (ECOG) performance status 2-0. Adherence of at least 75 % of the program or minimum of 6 sessions. Exclusion Criteria: Surgery without a minimum of 3 weeks of prehabilitation time. Unstable respiratory or heart disease. Locomotor or cognitive limitations that makes not feasible the adherence to the program. Refusal of the patient.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Usual care<br>Control group will follow the standard preoperative measures Enhanced Recovery After Surgery (ERAS®) established in the protocols of our hospital. Standard preoperative measures: recommendation of nutritional and physical activity and advice to stop smoking and reduce alcohol intake; optimization of preoperative pathologies including anaemia. An information document on ERAS® measures in our center will be attached to all of them. | |
| Experimental: Multimodal prehabilitation<br>Patients following the standard preoperative policies of our institution and the multimodal prehabilitation program | Other: Multimodal Prehabilitation<br>* High-intensity endurance exercise training program and physical activity promotion remotely controlled with ICT (information and communications technologies). Nutritional counselling to achieve protein intake of 1.5-1.8 g/kg and whey protein supplements. Psychological intervention including motivational interview, mindfulness meditation and cognitive behavioral therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of postoperative complications | Any deviation from the normal postoperative course and according its severity to the Clavien-Dindo classification, will be considered a complication. A comprehensive complication index (CCI) scale will be used which assigns a value to each Clavein-Dindo level so a weighted average of the severity of complications can be calculated not only in a qualitatively way, but also numerically. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital and ICU (intensive care unit) length of stay |  | postoperative 30 days | 
| Compliance to the ERAS program. | Percentage of items of ERAS program that were completed. Key aspects of this protocol include prevention of prolonged fasting allowing oral intake of clear fluids up to 2 hours before induction of anaesthesia, carbohydrate loading, avoidance of mechanical bowel preparation except if a bowel resection is scheduled, thromboprophylaxis; pre-, intra-, and post-operative euvolemia via goal directed fluid therapy, maintenance of normothermia, intraoperative and postoperative opioid-sparing multi-modal analgesia, avoidance the use of surgical drains, early removal of the urine catheter, and an emphasis on early ambulation and feeding. | postoperative 30 days | 
| Interval of days between surgery and the start of chemotherapy |  | From date of surgery up to 6 months | 
| Preoperative and postoperative aerobic capacity | Maximum production of carbon dioxide in ml/min during high intensity cardiopulmonar exercise. | baseline, 1 and 3 month post intervention | 
| Cost-effectiveness | Cost of treatment in the hospital in Euros including prehabilitation and postoperative recovery. | Baseline up to 30 days after surgery | 
| Health Related Quality of Life assesed by EORTC QLC-C30 |  | Baseline and 1 month postoperative | 
| Incidence of cognitive deficit | Cognitive assessment based on validated neuropsychological test: T @ M (; Digits WAIS III (Wechsler Adult Intelligence Scale-Third Edition) | Baseline and 1 month postoperative | 
| Overall and disease-free survival of the study groups |  | 5 years | 
| Nutritional status | GLIM (includes hand-grip) | Baseline and 1 month postoperative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nutrition, Prehabilitation, Advanced ovarian cancer, cytoreductive surgery, postoperative complications, exercise training, physical activity, mindfulness meditation