Geriatric oncology multidomain intervention study to prevent cognitive impairment among older Indian patients with cancer receiving chemotherapy: A randomized controlled trial (GOCOG)

Aim To establish the efficacy of a 3-month multidomain intervention in decreasing chemotherapy-related cognitive decline in older patients with cancer receiving chemotherapy, compared to usual care.

Study population and setting

Patients aged 60 years and over with a diagnosis of malignancy and who are planned for chemotherapy will be considered for the study. The study will be conducted in the Departments of Medical Oncology, Psycho-oncology, Physiotherapy, and Occupational Therapy at the Tata Memorial Center in Mumbai, Maharashtra, India.

Study Design

All patients who satisfy the above criteria and consent to participate in the study will be randomized 1:1 between two arms using simple computer-generated randomization. Patients will be stratified for age (60-69 years and 70 years and above), sex (male and female), ECOG PS (0-1 and 2), disease (lung cancer vs gastrointestinal cancer vs others), and type of chemotherapy regimen (combination chemotherapy vs monotherapy). Patients will undergo an initial multidomain geriatric assessment, and cognition will be assessed using the FACT-Cog.

Treatment Arm:

In Experimental arm, patient will be taught how to do some simple exercises, and then will be asked to walk or do some other simple aerobic exercise for about 30 minutes a day for about 3 days in a week, for 3 months. They will also be taught some simple resistance exercises with elastic bands called TheraBands, or just simple resistance exercises, which will be asked to do 2 sets (doing each movement 6 to 8 times). All these exercises will be taught to patient by a member of the study team and will be asked to maintain a diary in which patient will regularly record the physical and mental exercises.

In Standard arm, patient will be put in the usual treatment group; there will be nothing extra that patient is asked to do, as a part of the study and will plan the as usual treatment.

Patients will undergo reassessment of cognition using FACT-Cog and objective assessment using ACE III after 3 months (+/- 2 weeks).

Compliance

The compliance for the interventions will be assessed as follows: For aerobic exercises, we will ask participants to record the daily step count, in patients who have the means to measure the step count (via smartwatches or smartphone apps). Patients and caregivers will be asked to maintain a diary with details regarding the resistance exercises, aerobic exercises, and cognitive training, which will include the date, the type of exercise done, and the total duration.

Sample size calculation

Our primary endpoint is the difference in the change in the mean FACT-Cog total score from baseline to 3-months in the intervention arm compared to that in the standard arm. Based on the study by Janelsins et al. (23), we assume that the mean change (decrease) from baseline to 3-months in the FACT-Cog total score will be 15.9, with a standard deviation of 30.8 in the standard arm (23). We hypothesize that the intervention group will experience a mean change of 5 points, i.e., a drop of 10 points less in the cognition score from baseline to 3 months of chemotherapy, which is considered the minimal clinically significant change. In order to test this hypothesis, an estimated total sample size of 364 (182 in each group) will be required to compare the mean change, considering a 30% attrition rate (based on clinical experience and the fact that this study will be conducted in older patients with cancer). This sample size will achieve an 80% power to detect differences between the mean change using a z-test with a 5% significance level. The first 50 patients randomized to the interventional arm will be considered for the feasibility portion of the study. Compliance to the interventions in at least 60% of the patients in the feasibility study will be considered sufficient to proceed with the rest of the study.