Frailty, Quality Of Life and Early Reversal of Temporary Defunctioning Stoma in Ovarian Cancer (FOLERO)

Frailty, Quality Of Life and Early Reversal of Temporary Defunctioning Stoma in Ovarian Cancer (FOLERO) : A Prospective Cohort Study to Determine the Effect of Frailty on Survival and to Assess Early Reversal of Temporary Intestinal Stoma

Complete macroscopic surgical resection (CMR) requires extensive surgery and combined with chemotherapy confers best chance of survival in advanced ovarian cancer. During cytoreductive surgery 11% of women require a temporary diverting intestinal stoma.

Unexpectedly, our results from a unique fully accounted for population demonstrate that survival was not improved when increasing the proportion of women in whom CMR was achieved and in a yet unidentified subgroup of women extensive surgery was detrimental. In these women surgical treatment should be omitted in favor of chemotherapy only. Accordingly, there is an imperative need to improve patient selection to surgical treatment.

In Sweden, we treat an unselected population of women in a public healthcare system, where 30% of women with are >75 years. Despite these circumstances guidelines on patient-selection are lacking.

Age is an imprecise variable to base clinical decisions on but must be considered with an aging population. The dynamics between physiological changes of aging, comorbidity and medical condition are included in the concept of frailty, that has gained little attention in oncology, despite their potential to stratify risk and mortality.

The FOLERO study is a prospective adequately powered national cohort study with aim to determine if frailty instruments may be used to select patient to surgical treatment. In addition, we test the feasibility of early stoma reversal after index cytoreductive surgery in a small phase I trial and follow our patients Health Related Quality of Life after state of the art surgical treatment.

Study Overview

• Status: Recruiting
• Conditions: Ovarian Cancer
• Intervention / Treatment: Other: Frailty and Quality of Life evaluation

Detailed Description

Hypothesis: Frailty is a predictor of poor survival Primary objective: To assess three different frailty instruments as predictors of survival Exposure: Frailty according to the three different frailty instruments evaluated Control: No frailty according to the three different frailty instruments evaluated Primary outcome measure: Overall survival

Secondary objectives (selection):

• To evaluate the effect of sarcopenia on postoperative outcome and survival
• To evaluate the effect of surgical extent on postoperative outcome and survival
• To describe the HRQoL and symptoms of the" Low anterior resection syndrome" after surgery

Phase I sub-study on the feasibility and safety of early stoma reversal (Karolinska University Hospital only)

Hypothesis: Early stoma reversal in select patients with advanced ovarian cancer is feasible and safe.

Primary objective: To assess the feasibility and safety of early closure of defunctioning stoma after upfront cytoreductive surgery in ovarian cancer Primary outcome measure : Feasibility and safety of early stoma reversal as measured by rate of anastomotic leakage, urgent re- operations and time-interval to adjuvant chemotherapy (defined cut-offs based on historic comparison in the study protocol)

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fihima M Yusuf, MSc; Phone Number: +46725815883; Email: fihima.mohamed-yusuf@regionstockholm.se

Study Locations

• Sweden
  • Gothenburg, Sweden, 41685
    • Not yet recruiting
    • Sahlgrenska University Hospital and Sahlgrenska Academy
    • Contact: Pernilla Dahm-Kähler, MD, Prof.; Phone Number: 0313434216; Email: pernilla.dahm-kahler@gu.se
    • Principal Investigator: Pernilla Dahm-Kähler, MD, Prof.
    • Principal Investigator: Charlotte Palmqvist, MD, PhD
  • Linköping, Sweden, 581 85
    • Recruiting
    • Linkoping University Hospital
    • Contact: Madelene Wedin, MD, PhD; Email: madelene.wedin@regionostergotland.se
    • Principal Investigator: Madelene Wedin, MD, PhD
  • Lund, Sweden, 22185
    • Not yet recruiting
    • Skåne University Hospital
    • Contact: Mihaela Asp, MD, PhD; Email: Mihaela.Asp@skane.se
    • Principal Investigator: Mihaela Asp, MD, PhD
    • Sub-Investigator: Päivi Kannisto, MD, Ass Prof
  • Solna
    • Stockholm, Solna, Sweden, 171 76
      • Recruiting
      • Karolinska University Hospital
      • Contact: Sahar Salehi, MD, Ass Prof; Email: sahar.salehi@regionstockholm.se
      • Contact: Daniel Hunde, MD; Email: daniel.hunde@regionstockholm.se
      • Sub-Investigator: Daniel Hunde, MD
      • Principal Investigator: Sahar Salehi, MD, Ass Prof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women with epithelial ovarian cancer scheduled for cytoreductive surgery with curative intent
• Age ≥18 years
• Signed written informed consent

Exclusion Criteria:

• Not able to understand the Swedish or English language
• Other diagnosis than ovarian cancer on final pathology

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Frailty; Single arm study evaluating frailty by assessment of questionnaires and three different frailty tools	Other: Frailty and Quality of Life evaluation; Frailty and Quality of Life evaluation after surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival time is calculated from the date of index surgery to the date of death (due to any cause), or for patients still alive to the date of last follow-up.	24 months after index surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year mortality	Mortality within 1-year after index surgery	12 months from index surgery
Health related quality of life (HRQoL) (QLQ-C30)	Assessed by validated questionnaire and comprise the European Organisation for Research and Treatment of Cancer (EORTC), Core Questionnaire (QLQ-C30)	At baseline, 12-15 weeks after index surgery and 12 months after index surgery
Health related quality of life (HRQoL) (QLQ-OV28)	Assessed by validated questionnaire and comprise the European Organisation for Research and Treatment of Cancer (EORTC), EORTC Quality of life Questionnaire Ovarian Cancer Module (QLQ)-OV28	At baseline, 12-15 weeks after index surgery and 12 months after index surgery
Health related quality of life (HRQoL) (QLQ-ELD14)	Assessed by validated questionnaire and comprise the European Organisation for Research and Treatment of Cancer (EORTC), EORTC Quality of life Questionnaire Elderly Module (EORTC-QLQ-ELD14)	At baseline, 12-15 weeks after index surgery and 12 months after index surgery
Health related quality of life (HRQoL) (EQ-5D-5L)	Assessed by validated questionnaire and comprise the European Organisation for Research and Treatment of Cancer (EORTC), EQ-5D-5L	At baseline, 12-15 weeks after index surgery and 12 months after index surgery
Low anterior resection syndrome (LARS)	Assessed by the validated LARS questionnaire	At baseline, 12-15 weeks after index surgery and 12 months after index surgery
Postoperative complications	Assessed by validated instruments, Clavien-Dindo Classification	30 days after index surgery
Readmissions	Assessed by review of hospital records from the day of discharge after index surgery	30 days after index surgery
Length of hospital stay	Assessed by review of hospital records	From date of index surgery to the date of discharge or at latest 90 days after index surgery
Extent of surgery vs survival	Measured by surgical complexity score (as defined by the Mayo and Karolinska Surgical Complexity scores) and Peritoneal Cancer Index (PCI) both by assessment at the preoperative multidisciplinary conference The agreement between preoperative and peroperative assessment of surgical extent needed to achive complete macroscopic resection.	Up to 60 months after index surgery
Sarcopenia vs post-operative outcome	Sarcopenia is measured by computed tomography and different muscle groups by different software programs (e.g. Coreslicer, Slice-o-matic etc.).	Up to 60 months after index surgery
Standard regimen of adjuvant chemotherapy	Standard regimen of adjuvant chemotherapy is defined as Carboplatin (AUC 5) and Paclitaxel (175 mg/m2) every 21 days for 6 cycles. Dose and frequency will be assessed by review of hospital records	At 1 year after index surgery
Time interval to adjuvant chemotherapy	Assessed by review of hospital records.	From index surgery to first infusion of adjuvant chemotherapy
Total number of hospital days and readmissions within90 days after index surgery	Total number of hospital days within 90 days after index surgery by review of hospital records	90 days after index surgery
Health economics	Health economics will be assessed by the Eq5D-5L validated instrument	At baseline, 12-15 weeks after index surgery and 1 year after index surgery
Recurrence or progression free survival	Defined as the time interval between index surgery and the date of recurrence or death, whichever comes first. For event-free patients recurrence free survival is the time between index surgery and the date for the last follow-up visit by review of medical records.	Up to 60 months after index surgery

Collaborators and Investigators

• Sponsor: Sahar Salehi
• Investigators: Study Director: Sahar Salehi, MD, PhD, Karolinska University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2024
• Primary Completion (Estimated): March 28, 2029
• Study Completion (Estimated): March 28, 2029

Study Registration Dates

• First Submitted: February 26, 2024
• First Submitted That Met QC Criteria: March 1, 2024
• First Posted (Actual): March 7, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Ovarian Neoplasms; Frailty; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: 2023-04696-01

Drug and device information, study documents

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