Trial Title:
FRAGINOC Study: Screening and Geriatric Assessment and Intervention in Older Patients With Epithelial Ovarian Cancer
NCT ID:
NCT05810701
Condition:
Ovarian Cancer
Frailty
Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Frailty
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
Rancomized clinical trial Combined observational study
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Other
Intervention name:
Comprehensive geriatric assessment and individualised physical training
Description:
Comprehensive geriatric assessment and relevant intervention (including medical and
pharmacological optimisation, nutritional, social and psychological intervention, among
others), and individualised physical training
Arm group label:
NACT and CGA+ physical training intervention
Summary:
Ovarian cancer (OC) is the fifth most common cause of cancer death. More than 40% are
older than 70 years. The standard treatment is radical surgery combined with
chemotherapy. More than 40% of the Danish patients will never undergo surgery. Frail and
immunodeficient older patients are at higher risk of complications, and immunomodulating
treatment as chemotherapy results in different outcomes in comparable patients. No
accurate validated screening tool to identify frail and immunodeficient OC women exists.
Optimization through comprehensive geriatric assessment (CGA) and physical training
before and during treatment may improve outcomes and decrease associated risks.
Aim: Primary endpoints will be to determine whether a CGA and physical training vs
standard of care can increase the proportion of patients later on referred to interval
debulking surgery, and examine the performance of validated screening tests in predicting
impairments in CGA. Other endpoints will be to evaluate if intervention can improve
completion of chemotherapy, to examine the association between frailty screening scores
and selected biomarkers with treatment outcomes, including complications and quality of
life, and ultimately to develop an improved frailty screening tool based on known
screening tools, functional tests and biomarkers identifying patients who will benefit
from CGA.
Method: This is a nationwide, randomized intervention study. Patients ≥70 years diagnosed
with primary OC at the Gynecological departments of Rigshospitalet, Odense and Roskilde
University Hospitals will be included. In an interdisciplinary collaboration between
medical specialists in oncology, gynecology and geriatrics, included patients will be
screened for frailty using validated screening tools and functional tests. Specific
biomarkers and immunologic profile will be assessed in all patients. Patients selected
for neoadjuvant chemotherapy will be randomized to receive CGA or standard of care.
Patients selected for primary debulking surgery or palliation will be followed in an
observational cohort.
Perspective: The development of a validated screening tool for frailty assessment and
immunological status will help us identify frail patients who may need optimization
before treatment, resulting in more patients getting optimal treatment (either surgery or
chemotherapy), prevent post-treatment complications and avoid palliative patients from
undergoing a redundant complex treatment.
Detailed description:
Introduction
Several studies have shown that a high percentage of patients with epithelial ovarian
cancer (EOC) are undertreated due to their age, even in the absence of comorbidity. On
the other hand, there seems to exist a group of frail patients unfit for extensive
treatment that are over-treated. Therefore, it is of great interest to identify the group
of older patients with EOC, who are frail and would benefit of a comprehensive geriatric
assessment and optimisation, including individualised physical training. Unfortunately,
no specific screening tool can be recommended or discouraged, and none of these tests are
validated in patients with EOC.
Immunodeficiency and biomarkers regarding nutritional status, strength, and general
health are not part of the standard evaluation, although several studies have shown a
correlation between these factors and the functional independence of older patients,
comorbidity, postoperative complications, tolerance to chemotherapy and quality of life.
In oncologic geriatrics a Comprehensive Geriatric Assessment (CGA - an examination
performed by an interdisciplinary geriatric team) can be performed before start of
treatment. Unfortunately, a complete CGA is both time and resource consuming, and the
impact of interventions in older patients with EOC has never been examined.
Hypothesis and purpose
Our hypothesis is that frail patients with advanced ovarian cancer can benefit from a
geriatric assessment and optimization, including physical training, increasing their
chances of referral to surgery and to get full oncological treatment. The investigators
believe that it is possible to develop a frailty screening tool with highly improved
accuracy by combining known frailty screening tests, functional tests, and relevant
biomarkers, which can help us select those patients who will benefit from a geriatric
assessment and intervention.
The clinical study is parceled out in two working projects, WP1 and WP2, which are
anchored at the departments of gynecology, geriatric medicine, and oncology at several
centers in Denmark.
- WP1: Geriatric assessment and intervention and its impact on treatment outcomes
examined in a cohort of older patients with EOC referred to NACT Primary endpoint:
To determine whether a CGA and tailored intervention vs. standard of care can
increase the proportion of patients referred to IDS.
Secondary endpoints are a)to evaluate whether a CGA and tailored intervention can improve
completion of chemotherapy, b) to investigate if CGA and a tailored intervention with
physical training vs. standard of care improves treatment outcome and quality of life.
- WP2: Impact of biomarkers, functional tests and immunological profile in assessing
frailty and as predictors of adverse treatment outcomes in a national cohort of
older EOC patients.
Primary endpoint: to examine the performance of three validated frailty screening tests
(G8, mG8, and Clinical Frailty Index (CFI)) in EOC patients in predicting impairments in
CGA.
Secondary endpoints are a)to examine whether adding functional tests, biomarkers, and the
immunological profile can improve the accuracy of the frailty screening tests b) to
examine whether the screening tool is predictive of patients achieving radical surgery
and completing oncological treatment, as well as predict adverse treatment outcomes
Method description
The FRAGINOC project is a multicenter study, where WP1 is a clinical randomized trial of
screening and intervention in older patients (≥70 years) with a diagnose of advanced EOC
(FIGO stage III-IV). WP2 is a prospective observational study, where patients from WP1
will be asked to participate. Furthermore, older patients (≥70 years) referred to PDS or
palliation will also be included. Patients will be evaluated at MDT conference, where
they will be referred to either PDS and chemotherapy or NACT or palliation. Those
referred to NACT will be re-evaluated at a second MDT conference after three cycles of
chemotherapy to decide whether they can be referred to IDS.
Screening
All included patients will be screened for frailty after the MDT conference using a
combination of the following tools:
- Questionnaires (Geriatric-8, modified Geriatric-8 and clinical frailty scale).
- Functional tests (hand grip test, 30 second chair test and 6 minutes walk test)
- Blood samples, which have all been validated previously although in other cancer
types.
These tests will be repeated after the second MDT conference (after 3rd cycle of
chemotherapy or before interval surgery)
Randomization and Intervention After the initial frailty screening, patients eligible for
primary chemotherapy will be randomized 1:1 to CGA and tailored intervention or standard
of care.
The intervention group will be evaluated by a geriatric specialist team examining
different domains of their health status with the help of different validated
questionnaires and tests, and tailored interventions will be made according to identified
needs in the assessed health domains following the geriatric evaluation.
The intervention will specifically include a tailored-made physiotherapy training program
of around 9-12 weeks duration, available in both physical and virtual versions. The
program consists on supervised resistance training two days a week, either at hospital
appointments or virtually from the patients' own home. Those patients who are not able to
make the virtual training will be followed up by phone twice a week by the
physiotherapist. Additionally, the training will be supported by a progressive walking
program measured with a Garmin Vivofit 4 activity tracker. Patients will be thoroughly
assessed by a physiotherapist during the training process. Nutritional supplements and
advice on sufficient nutrition will be provided according to current clinical guidelines.
Patient-reported outcomes Measures (PROMs) All patients will be asked to complete the
European Organization for Research and Treatment of Cancer's Quality of Life
Questionnaire - Ovarian Cancer Module (EORTC QLQ C-30, QLQ-OV28) and the supplemental
Elderly Cancer Patients Module questionnaire (ELD-14), as well as European Quality of
Life- 5 dimensions- 5 levels questionnaire (EQ-5D-5L for cost-utility analysis, at
inclusion, after three cycles of chemotherapy, and at the end of treatment.
When assessing the quality of recovery, the QoR-15 questionnaire will be used and
evaluated before surgery and 72 hours after PDS or IDS.
Statistical plan/recruitment consideration According to the literature and clinical
experience, increasing the number of patients who receive surgery from the present 57 %
to 77 % is clinically relevant and possible. To detect a difference of 20 % and obtain a
type I error rate of 5% and a power of 80%, a sample size of 86 patients per study arm
will be needed. To account for an expected dropout rate of ~20%, it was decided to
increase this number to a group size of 100. Thus, a total of 206 patients referred to
NACT will be included in the study (WP1 only). Patients referred to PDS will be followed
in an observational design. For the last three years, 130 patients fulfilling the
inclusion criteria have been treated at RH, OUH, HUH, and SUH each year. Thus, inclusion
is expected to run over 2-3 years.
Data will be collected prospectively (demographic, clinical, pathologic, and results from
frailty screening, functional tests, blood tests, and intervention effects), and recorded
in predesigned RedCap. PRO will be completed by the patients either electronically and
registered directly in RedCap, by phone calls or delivered in hand to the Ph.D. student
or research nurses. Life-long follow-up data on overall survival will be obtained from
the Danish Hospital Registry through linkage with a personal identification number.
Logistic regression will be used to evaluate change over time in ordinal categorical
values. Independent T-tests will be used to evaluate in-group and between-groups
differences. Kaplan-Meier method and Cox regression analyses will be used to analyze
Progression Free Survival.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Newly diagnosed ovarian cancer
- Capable of understanding written and oral danish
Exclusion Criteria:
- Other active cancers in the preceding 5 years
- Severe psychiatric disease
Patients referred to primary debulking surgery will be followed in a observational design
Gender:
Female
Gender based:
Yes
Gender description:
Women as only women are diagnosed with ovarian cancer
Minimum age:
70 Years
Maximum age:
120 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Odense University Hospital
Address:
City:
Odense
Zip:
5000
Country:
Denmark
Status:
Recruiting
Contact:
Last name:
Tine Schnack, MD, PhD
Phone:
+45 65412336
Email:
tine.henrichsen.schnack@rsyd.dk
Contact backup:
Last name:
Cristina Daviu Cobian, MD
Phone:
+45 47324010
Email:
maria.cristina.daviu.cobian@rsyd.dk
Facility:
Name:
Vejle Hospital
Address:
City:
Vejle
Zip:
7100
Country:
Denmark
Status:
Recruiting
Contact:
Last name:
Cristina Daviu Cobian, MD
Phone:
+45 47324010
Email:
maria.cristina.daviu.cobian@rsyd.dk
Facility:
Name:
Zealand University Hospital
Address:
City:
Roskilde
Zip:
4000
Country:
Denmark
Status:
Recruiting
Contact:
Last name:
Cristina Daviu Cobián, MD
Phone:
+45 47324010
Email:
maria.cristina.daviu.cobian@rsyd.dk
Facility:
Name:
Copenhagen University Hospital Rigshospitalet
Address:
City:
Copenhagen
Zip:
2100
Country:
Denmark
Status:
Recruiting
Contact:
Last name:
Jakob Ohm Oreskov, MD
Phone:
+45 38688591
Email:
jakob.ohm.oreskov@regionh.dk
Facility:
Name:
Herlev and Gentofte Hospital
Address:
City:
Herlev
Zip:
2730
Country:
Denmark
Status:
Recruiting
Contact:
Last name:
Jakob Ohm Oreskov, MD
Phone:
+45 38688591
Email:
jakob.ohm.oreskov@regionh.dk
Start date:
February 1, 2023
Completion date:
December 31, 2027
Lead sponsor:
Agency:
Odense University Hospital
Agency class:
Other
Collaborator:
Agency:
Rigshospitalet, Denmark
Agency class:
Other
Collaborator:
Agency:
Herlev Hospital
Agency class:
Other
Collaborator:
Agency:
Zealand University Hospital
Agency class:
Other
Source:
Odense University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05810701
