The Use of PatientReportedOutcomes (PRO)- CTCAE by Melanoma Patients Receiving Immunotherapy

Study Overview
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Brief Summary
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This study evaluates if melanoma patients who report their side effects to immunotherapy weekly by the use of ePRO-CTCAE will experience an overall reduction of grade 3 and 4 events with 50% compared to routine monitoring carried out every 3 weeks.

Detailed Description
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Hypothesis: - Melanoma patients who report their side effects to immunotherapy by the use of PRO-CTCAE (Common Terminology Criteria for Adverse Events) will experience an overall reduction of grade 3 and 4 events with 50% compared to routine monitoring. Aim: Primary endpoint: To examine if the electronic tool PRO-CTCAE used on a weekly basis by patients receiving immunotherapy to supplement standard AE monitoring, results in cutting the frequency of grade 3 or 4 adverse events during treatment by 50% compared to patients who get a standard AE monitoring schedule every 3 weeks. Secondary endpoints: 1)To examine if the time patients experience grade 2 or higher toxicity, differs in the two groups 2)To examine if more symptoms are reported in the intervention group 3) To examine if there is a difference between the 2 group when it comes to number of extra out-patient visits, days in hospital, telephone consultations and days in prednisone therapy 4) To examine if PRO-CTCAE is implementable in daily practice (will be explored in study 2 and 3). Exploratoty endpoint: To examine, using both qualitative and quantitative data, patients´ and clinicians´ experiences with the e-Health intervention to monitor side effects during treatment with immunotherapy in routine clinical practice. Method: All patients who are about to receive immunotherapy for the treatment of malignant melanoma at the Department of Oncology, Odense University Hospital (OUH), will be asked to participate. Patients who meet eligibility criteria will be randomized in a 1:1 ratio to either the intervention arm (the use of PRO-CTCAE) or the control arm (standard AE monitoring schedule). Approximately 70 patients in each arm. Inclusion will take place between September 2016 and July 2018. Patients in the intervention arm will report their events weekly for the first 12 weeks of treatment. Clinical staff and patients in the intervention arm will receive instructions on how to use the Ambuflex system to complete the electronic PRO-CTCAE questionnaire (patients) and include the reports in daily practice (clinical staff). Assistance from clinical staff will be provided to patients when needed. Moreover, hospital staff will receive education and written instructions on how to handle the weekly feedback form the patients in the intervention arm. Evaluation: Studies show that 16% of patients treated with Pembrolizumab/Nivolumab experience grade 3 or 4 side effects during treatment. When it comes to Ipilimumab, the number is 27% and when the drugs are combined the number is as high as 55 %. It is however not all adverse events which the patients can report themselves and when biochemical AEs are deducted, it is estimated that the numbers suitable for self-reporting are as follows: Pembrolizumab/Nivolumab 10%, Ipilimumab 20%, Combination therapy 40%.The primary endpoint of the randomized trial is to reduce the frequency of grade 3 or 4 side effects from 10% to 5% for pembrolizumab /Nivolumab, from 20% to 10 % for Ipilimumab and from 40% to 20% for the combination theory. Realistically, 140 patients can be included in the course of 2 year according to the Danish Melanoma Group. A level of significance of 0.2 is accepted reaching a power of 0.61 for Pembrolizumab/Nivolumab, 0.80 for Ipilimumab) and 0,96 for the combination therapy. These numbers are acceptable due to the fact that this is a pilot study; PRO-CTCAE has not been used in connection with immunotherapy prior to this study and only in a few projects with other patients in Denmark. Moreover, it is prioritized that the Department of Oncology, OUH is the only site, so that the applicant can make sure that all relevant patients are recruited and that clinicians are constantly reminded of the project. Also, the applicant will be able to teach both patients and clinicians on how to use the tool. All in all, the collection of data will be easier and of a higher quality when the study is only being conducted in one site.

Official Title
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The Use of PRO-CTCAE by Patients Receiving Immunotherapy for the Treatment of Malignant Melanoma

Conditions
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Adverse Effects

Intervention / Treatment
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* Device: Tablet: Samsung Galaxy Tab A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ≥18 years of age who read and understand Danish, who have been diagnosed with malignant melanoma, who are about to be treated with immunotherapy for their disease (1st and 2nd line, mono-therapy and combination therapy). Moreover, patients must have signed and dated a written informed consent form in accordance with regulatory and institutional guidelines and 6) be willing and able to comply with the completion of PRO-CTCAE and other required questionnaires. Exclusion Criteria: - None

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention<br>Patients report their adverse events on a tablet once a week (intervention) as a supplement to having them monitored every 3 weeks by a physician | Device: Tablet: Samsung Galaxy Tab A<br> <br> |
| No Intervention: Control<br>Patients have their side effects monitored by a physician every 3 weeks (control) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients who experience drug-related grade 3 or 4 adverse events assessed by CTCAE 4.0 will be reduced by 50% in the intervention arm compared to patients in the control arm |  | The first 6 months of treatment with immunotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The time patients experience grade 2 or higher toxicity assessed by CTCAE, differs in the intervention arm and the control arm respectively |  | The first 6 months of treatment with immunotherapy | 
| The number of drug-related adverse events assessed by CTCAE 4.0 reported in the intervention will be higher compared to the adverse events reported in the control arm |  | The first 6 months of treatment with immunotherapy | 
| The number of contacts to the hospital will be higher in the intervention arm compared to patients in the control arm |  | The first 6 months of treatment with immunotherapy | 
| The number of hospitalizations are fewer in the intervention arm compared to the control arm. |  | The first 6 months of treatment with immunotherapy | 
| Patients in the intervention arm receive a lower accumulated prednisone dose compared to patients in the control arm |  | The first 6 months of treatment with immunotherapy | 
| Patients in the intervention arm have a longer progression free survival compared to patients in the control arm | PFS is estimated using Kaplan Meier method and differences estimated using logrank test | Estimation of median PFS and progression free survival rate at 6, 12 and 24 months | 
| Patients in the intervention arm have a longer overall survival compared to patients in the control arm | OS is estimated using Kaplan Meier method and differences estimated using logrank test | Estimation of median OS and overall survival rate at 6, 12 and 24 months | 
| Patients in the intervention arm have a better QoL compared to patients in the control arm | EQ-5D-5L and FACT-M questionnaires are used to examine the outcome | baseline, week 24 and week 48 | 
| The QoL of patients who experience grade 3 or 4 irAEs vs. no grade 3 or 4 irAEs | EQ-5D-5L and FACT-M questionnaires are used to examine the outcome | baseline, week 24 and week 48 |