Stratification of Patients in Oncogeriatrics and Personalization of Interventions

Study Overview
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Brief Summary
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Multicenter randomized controlled trial. Patients will be randomly assigned to the control group or the intervention group in each of the health centers. The control group will receive the usual care, while the intervention group will add an individualized physical exercise program to the usual care. Cancer is a disease of the elderly. More than 65% of all malignancies affect this population. At the same time, the incidence of cancer cases increases and the need to better understand the biological characteristics of the disease, as well as those of the elderly who suffer from it, is highlighted. Oncogeriatrics is the area that addresses the care of the elderly patient with cancer, taking into account that physiological aging causes older people to have their own characteristics that require a differential approach in care. The low inclusion in clinical trials of elderly patients and the few specific trials carried out in this subpopulation together with the progressive aging of the population mean that the development of this area has become a priority in health policies. Therefore, there is a need to focus the research area on supervised physical exercise in older people with cancer in an innovative way, with the aim of generating new hypotheses that overcome existing limitations and facilitate the introduction into the health system of this type of interventions.

Detailed Description
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It seems useful to have instruments that help to objectively evaluate the fragilty and comorbidity of patients with the intention of adequately indicating the administration of antineoplastic treatment. In addition, nowadays, with the arrival of new less toxic treatments, it is essential to make a good selection of the patients to be treated, since there is a risk of treating patients who are not going to benefit from an active treatment just for having more comfortable medications and with less toxicity. There are several instruments that can help to better select the patients that the investigators are going to treat and to select the supportive care that can help to better tolerate the proposed treatments while maintaining the best possible quality of life. Some of those instruments are aimed at detecting fragility such as comprehensive geriatric assessment. They identify in more detail the different vulnerabilities that can affect the patient in the benefit vs. toxicity balance of the treatment and in the long-term quality of life Many authors emphasize the importance of including a physical exercise program during and after cancer treatment. Despite this, older people with cancer usually have low levels of physical activity, and few adhere to the recommendations they receive from health centers. For this reason, involving older people with cancer in a regular physical activity program becomes a challenge for those in charge of health centers. Some studies have shown that physical exercise can reduce the usual loss of functional capacity and reduce frailty during cancer treatment. On the other hand, physical exercise can help reduce pain, toxicity and improve the completion rate of systemic treatment. Recent studies have found that physical exercise on the days of chemotherapy cycles is safe and may be beneficial in reducing neuropathy and maintaining physical well-being. Additionally, physical exercise can impact one of the most common and strenuous adverse effects of cancer treatment, fatigue.

Official Title
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Stratification of Patients in Oncogeriatrics and Personalization of Interventions

Conditions
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Oncology, Solid Tumor, Adult

Intervention / Treatment
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* Other: Physical exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 70 or over. Solid cancer. Candidates for systemic treatment (chemotherapy, hormone therapy, biological therapies or immunotherapy) if the time that has elapsed since the last dose of treatment has been at least 1 month (washout period). Patients with breast, gynecological, lung, pleural, digestive, urological, ENT area, sarcomas, brain tumors, melanomas and patients with tumors of unknown origin will be included.Regarding tumor type and stage for patients with lymphoma: 1) Diffuse large B-cell NHL: include stages I-II if Bulky (>7.5 cm) or R-IPI>1. 2) Hodgkin lymphoma: stages I-II if Bulky (>10 cm). 3) Follicular NHL and marginal NHL without GELF treatment criteria. 4) 80 years old receiving 6 R-mini CHOP cycles. Exclusion Criteria: ECOG ≥3 cases of advanced dementia serious psychiatric illnesses Lack of basic fluency in the Basque or Spanish language those patients unable to get up from the chair and walk independently with or without auxiliary device. Neither will those patients who participate in other studies in which they are undertaking a physical exercise program be included. Absolute or relative contraindications in which the risk of adverse effects outweighs the possible benefits such as unstable angina, acute symptomatic heart failure ...

Ages Eligible for Study
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Minimum Age: 70 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control group<br>The control group will receive the usual care and hygiene recommendations of the movement | |
| Experimental: Interventionist group<br>The interventional group will add an individualized physical exercise program to the usual care. | Other: Physical exercise<br>* Physical exercise<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short Physical Performance Battery | Short Physical Performance Battery (SPPB) evaluates balance, gait ability, and leg strength using a single tool. The score for each part is given in categorical modality (0-4). The best score will be 12 points. 1 point of change in the total score has demostrated to be of clinical relevance. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Integral Geriatric Assessment -Socio-familial situation: | Abbreviated Gijón Scale (3-15 pts) | 12 weeks | 
| Integral Geriatric Assessment - Basic Activities of Daily Living ( BADL): | Barthel Index (0-100 pts) | 12 weeks | 
| Integral Geriatric Assessment -Instrumental Activities of Daily Living (IADL): | Lawton´s test (0-8 pts) | 12 weeks | 
| Integral Geriatric Assessment -Cognitive function: | Pfeiffer test (0-10 pts) | 12 weeks | 
| Integral Geriatric Assessment - Depression: | Yesavage test-short form (0-15 pts) (Yes/No) | 12 weeks | 
| Integral Geriatric Assessment -Nutritional status: | MNA-SF test (0-14) | 12 weeks | 
| Integral Geriatric Assessment -Polypharmacy: | Number of chronic drugs consumed by the patient | 12 weeks | 
| Integral Geriatric Assessment - Geriatric syndromes: | Immobility and pressure ulcers (Yes/No); instability and falls (Yes/No); urinary and faecal incontinence (Yes/No); dementia and acute confusional syndrome ( Yes//No); malnutrition (Yes/No); alterations in sight and hearing (Yes/No);constipation, faecal impaction (Yes/No);depression/insomnia (Yes/No) | 12 weeks | 
| Integral Geriatric Assessment -Pain: | VAS (0-10 pts) | 12 weeks | 
| Integral Geriatric Assessment - Emotional distress: | Stress thermometer (0-10 pts) | 12 weeks | 
| Cognitive function | - Montreal Cognitive Assessment (MOCA) test (0-30 pts) | 12 weeks | 
| Anthropometry - Weight: | Unit of measure: kg | 12 weeks | 
| Anthropometry - Height: | Unit of measure: cm | 12 weeks | 
| Anthropometry -Waist, hip and calf circumference: | Unit of measure: cm | 12 weeks | 
| Anthropometry -Blood pressure: | - Unit of measure: mmHg | 12 weeks | 
| Anthropometry 1: - Bioimpedance (in some centers) 1 | · Resistance (Ω) | 12 weeks | 
| Anthropometry 2: - Bioimpedance (in some centers) 1 | · Phase angle (º) | 12 weeks | 
| Biomarkers>> a.1 Inflammation markers (pg/ml or ng/ml): | - Interleukins 1beta, 2, 4, 6, and 8 (IL-1 b, IL-2, IL-4, IL-6, and IL-8/CXCL8). | 12 weeks | 
| Biomarkers>> a.2 Inflammation markers (pg/ml or ng/ml): | - Tumor necrosis factor alpha (TNFa) | 12 weeks | 
| Biomarkers>> a.3 Inflammation markers (pg/ml or ng/ml): | - Interferon gamma (IFN) | 12 weeks | 
| Biomarkers>> a.4 Inflammation markers (pg/ml or ng/ml): | - C-reactive protein (CRP) | 12 weeks | 
| Biomarkers>> a.5 Inflammation markers (pg/ml or ng/ml): | - Brain-derived neurotrophic factor (BDNF) | 12 weeks | 
| Biomarkers>> a.6 Inflammation markers (pg/ml or ng/ml): | - CMV serology | 12 weeks | 
| Biomarkers>> b.1 Endocrine-nutritional and muscle wasting markers (pg/ml or ng/ml): | - Insulin-derived growth factor (IGF-1). | 12 weeks | 
| Biomarkers>> b.2 Endocrine-nutritional and muscle wasting markers (pg/ml or ng/ml): | - Dehydroepiandrosterone sulfate (DHEA sulfate) | 12 weeks | 
| Biomarkers>> b.3 Endocrine-nutritional and muscle wasting markers (pg/ml or ng/ml): | - Vitamin D | 12 weeks | 
| Biomarkers>> b.4 Endocrine-nutritional and muscle wasting markers (pg/ml or ng/ml): | - Albumin | 12 weeks | 
| Biomarkers>> c. Hematological (AU): | Biomarkers in the cell fraction of blood samples. Panel of 7 genes related to aging and frailty in RNA extracted from blood leukocytes, by quantitative PCR (qPCR): EGR1, Hsa-miR454, DDX11L1, G0S2, GJB6, CXCL8 and NSF. This panel has been developed at Biodonostia as a diagnostic and frailty stratification tool (European Patent Application EP3599286). | 12 weeks | 
| Functional assessment and frailty: - Steep Ramp test (A) | >Heart rate (bpm) | 12 weeks | 
| Functional assessment and frailty: - Steep Ramp test (B) | >Time spent cycling (min/sec) | 12 weeks | 
| Functional assessment and frailty: - Steep Ramp test (C) | > Maximum W | 12 weeks | 
| Functional assessment and frailty: - Frailty | G8 scale ( 0-17); Fried Frailty Phenotype (0-5 pts) | 12 weeks | 
| Functional assessment and frailty: - Dynamic balance: | 8 Foot Up and Go Test (8FUGT) (sec) | 12 weeks | 
| Functional assessment and frailty: - Physical activity: 1.Accelerometry | Sleep efficiency (%) | 12 weeks | 
| Functional assessment and frailty: - Physical activity: 2. Accelerometry | Moderate too vigorous physical activity (min/d) | 12 weeks | 
| Functional assessment and frailty: - Physical activity: 3. Accelerometry | Sedentary time (h/d) | 12 weeks | 
| Functional assessment and frailty: - Physical activity: 4. Accelerometry | Light physical activity (min/d) | 12 weeks | 
| Patient-reported outcomes (PRO): -Fatigue: | EORTC QLQ-FA12 | 12 weeks | 
| Patient-reported outcomes (PRO): - Quality of life: | EORTC QLQ-C30 | 12 weeks | 
| Patient-reported outcomes (PRO): - Nutrition: | Simplified Nutritional Appetite Questionnire | 12 weeks | 
| Patient-reported outcomes (PRO): - Cognition: | Cognitive Failures Questionnaire | 12 weeks | 
| Patient-reported outcomes (PRO): - Physical activity: | Godin Physical Activity Questionnaire | 12 weeks | 
| Adverse events (CTCAE) | Treatment discontinuation (Yes/ No) Dose reduction (Yes/ No) Percentage of treatment completed (Yes/ No) Completion of treatment (Yes/ No) | 12 weeks | 
| Factors related to physical exercise adherence | Beliefs, barriers, facilitators and self-efficacy in relation to physical exercise ( self-developed questionnaire) | 12 weeks | 
| Intervention assessment - Follow-up of the intervention | Self- developed questionnaire | 12 weeks | 
| Intervention assessment - Adverse events associated with the intervention | Self- developed questionnaire | 12 weeks | 
| Intervention assessment - Satisfaction with the intervention | Self- developed questionnaire | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fragility, physical exercise, biomarkers, oncogeriatrics