Impact of Telemonitoring for the Management of Side Effects in Patients With Melanoma, Lung or Renal Cancer, Treated With Immunotherapy Combination of Nivolumab and Ipilimumab or Adjuvant Nivolumab Monotherapy

Study Overview
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Brief Summary
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The ipilimumab and nivolumab combination is now part of the standard of care for the treatment of melanoma, renal and lung cancer patients. Grade 3/4 adverse events (AEs) occur in 30 to 60% of patients included in clinical trials. Grade 3/4 AEs are more frequently observed (50-60% of patients) in melanoma because ipilimumab is administrated at 3mg/kg in this population. Among these AEs, early detection of immune related AEs is critical to an adequate medical management. In this context, dedicated tools for remote monitoring of these patients are crucial. The investigators developed within the Immucare consortium a simplified medical questionnaire which is addressed weekly to the patients. This questionnaire along with an algorithm gives to the clinician regular feedback on their patients' general symptoms. The investigators herein want to evaluate in a randomized prospective trial the efficacy of this remote monitoring to reduce the time between the start of AE and the reporting to the medical team, which could lead to detect and treat earlier AEs induced by nivolumab and ipilimumab in the melanoma, lung and renal cancer patients' population.

Official Title
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Impact of Telemonitoring for the Management of Side Effects in Patients With Melanoma, Lung or Renal Cancer, Treated With Immunotherapy Combination of Nivolumab and Ipilimumab or Adjuvant Nivolumab Monotherapy

Conditions
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Melanoma, Lung Cancer, Renal Cancer

Intervention / Treatment
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* Behavioral: Tele-monitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Patients diagnosed with melanoma, or lung cancer or renal cancer Patients starting a treatment with a combination of immunotherapy of nivolumab + ipilimumab (NB: patients who have already received immunotherapy in the past may be included) Patients comfortable with the use of digital tools and computing Patients who agree to participate to the telemonitoring and signed consent form Exclusion Criteria: Pregnant, parturient and lactating women Patients under legal protection measure or deprived of their liberty Patients not affiliated to a social security scheme (schemes such as the AME) or beneficiaries of a similar regime (foreign person, outside the EU)

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Experimental: Tele-monitoring group<br>In the experimental group, in addition to routine practice, each patient will benefit of a tele-monitoring of one year, and a long term follow-up up to 5 years to evaluate the Overall Survival and the Progression-Free Survival. Quality of life questionnaire will also be filled in at inclusion, M3 and M12. 50 patients are expected in this arm. | Behavioral: Tele-monitoring<br>* The tele-monitoring will consist in filling in a specific questionnaire once a week in the first 6 months, every 2 weeks until 12 months, and on-demand (in case of upcoming toxicity, at any time). These questionnaires will be reviewed by a coordinating nurse. According to the result of the questionnaire, the coordinating nurse will adapt patients' management, either by giving them a phone call, or inviting them to directly contact their medical department, or even plan an emergency hospitalization if necessary. The coordinating nurse will closely work with the investigator to adapt patients' management. Quality of life questionnaire (FACT-G) will also be filled in at inclusion, M3 and M12.<br>|
| No Intervention: Control group<br>In the control group, patients will have a routine follow-up as per institutional practice, and a long term follow-up up to 5 years to evaluate the Overall Survival and the Progression-Free Survival. Quality of life questionnaire will also be filled in at inclusion, M3 and M12. 50 patients are expected in this arm. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delay between the start of a side effect and reporting to the medical team (average number of days per patient). | The delay between the start of a side effect and medical information will be calculated for each AE and average per patient in each of the two groups studied, with its 95% confidence interval.The delays of the two groups will be compared using a Mann-Whitney test. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of morbidity based on CTC-AE v5 (all toxicities) | Levels of morbidity based on CTC-AE v5 (all toxicities) will be compare using a generalised log linear regression. In case of several AEs, the average medical information per patient will be considered. | 12 months | 
| Number of treatment interruptions and number of days of treatment delays interruptions, number of treatment discontinuation, number of dose reductions and and percentage of dose reduction | Number of treatment interruptions and number of days of treatment delays interruptions, number of treatment discontinuation, number of dose reductions and and percentage of dose reduction will be compared in the two groups using a Mann-Whitney test | 12 months | 
| Number of admissions in the emergency room | Number of admissions in the emergency room will be compared in the two groups with a Wilcoxon rank sum test. The rate of admissions per patient-years will be calculated and compared between the 2 groups with a Negative Binomial generalized linear regression model accounting for overdispersed data and correlated events, using the log of follow-up time as an offset. | 12 months | 
| Number of unplanned hospitalizations | Number of unplanned hospitalizations will be compared in the two groups with a Wilcoxon rank sum test. The hospitalizations per patient-years will be calculated and compared between the 2 groups with a Negative Binomial generalized linear regression model accounting for overdispersed data and correlated events, using the log of follow-up time as an offset. | 12 months | 
| Number of contact with general practitioner | Number of contact with general practitioner will be compared in the two groups with a Wilcoxon rank sum test. | 12 months | 
| benefit for clinicians: interview of clinicians on their opinion on the self-monitoring, evaluation to the impact on the consultations during the first year of treatment, assessed with satisfaction questionnaires | benefit for clinicians will be compared in the 2 groups with adequate test according to the retained satisfaction scale | Month 12 | 
| Number of AE identified by clinicians | Number of AE identified by clinicians will be compared in the two groups with a Wilcoxon rank sum test. In addition, the competitive risk of death with the recurrent events process will be explored using a joint frailty model (Rondeau V. et al. Joint frailty models for recurring events and death using maximum penalized likelihood estimation: application on cancer events. Biostatistics (2007), 8, 4, pp. 708-721). | 12 months | 
| Overall quality of Life assessed with standardized QoL questionnaires (FACT-G) | Overall quality of Life will be described and compared between the two groups with the Student t-test, or the Wilcoxon rank-sum test in case of non-normality of the distributions. All data recorded at the follow-up visits will be considered, whatever the actual date of the visit | 12 months | 
| Adherence: The number of full symptoms report completions and adherence to the completion schedule | Adherence will be described in the experimental group. All data recorded at the follow-up visits will be considered, whatever the actual date of the visit. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunotherapy, Tele-monitoring, nivolumab, ipilimumab