Evaluation of Digital Symptom Monitoring in Patients with Advanced Clear-Cell Renal Carcinoma Treated with Cabozantinib and Nivolumab

The primary objective of this study is to evaluate the impact of **digital monitoring** of self-reported symptoms (PROs-CTC-AEs) on the management of treatment adjustments for patients with advanced clear-cell renal carcinoma (RCC) treated with cabozantinib plus nivolumab. This assessment is crucial as it aims to optimize treatment efficacy and safety during the first 3 months of the combined treatment in a real-life setting.

Secondary objectives include:

• Regular follow-up of self-reported symptoms during the first 6 months of the combination therapy.
• Evaluation of symptom improvement after treatment adjustment.
• Characterization and evaluation of regular follow-up of patient-reported fatigue.
• Longitudinal assessment of general health-related quality of life (QoL) and pain.
• Assessment of the feasibility of regular follow-up of patient-reported outcomes (PROs) in real life.
• Evaluation of parameters impacting treatment compliance.
• Assessment of treatment duration.
• Evaluation of clinical outcomes of the cabozantinib plus nivolumab association, focusing on objective and overall response rates at 3 and 6 months post-initiation.
• Assessment of progression-free survival (PFS) according to treatment adjustments.
• Collection of patient and physician satisfaction with digital follow-up at 3 and 6 months.
• Evaluation of tolerability among a subgroup of frail elderly patients.
• Sub-group analyses considering the IMDC criteria.
• Characterization and description of warning adverse reactions requiring therapeutic adaptation.
• Characterization of alerts issued by digital monitoring, including frequency and impact on dose adjustment and treatment discontinuation.

The clinical trial focuses on patients diagnosed with **kidney cancer**, specifically those with a clear-cell component of Renal Cell Carcinoma (RCC). The study population includes both male and female participants aged 18 years and older. Participants are required to have no prior systemic treatment for RCC and must have a physician-initiated decision to be treated with cabozantinib and nivolumab in combination, according to approved local labels. The trial does not include a vulnerable population. Participants must be affiliated with an appropriate social security system and have provided informed consent prior to any trial-related activities. The sponsor has not provided information regarding the total number of participants in the study. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the impact of digital monitoring of self-reported symptoms on the management of treatments for patients with advanced clear-cell renal carcinoma. This study involves the administration of **cabozantinib** and **nivolumab** in combination, with the primary objective of assessing treatment adjustments based on weekly digital monitoring of patient-reported outcomes. The trial is structured as a randomized, double-blind, controlled study, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby minimizing bias. The trial is authorized to commence on July 17, 2025, and is expected to conclude by October 1, 2027, with an estimated recruitment start date of April 1, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of renal cell carcinoma, and prior treatment history. Following successful screening, participants will be enrolled in the study and will attend regular follow-up visits to monitor treatment efficacy and safety. These visits will include assessments of digital monitoring data to guide any necessary adjustments in treatment management. The end-of-study visit will occur at the conclusion of the treatment period, or earlier if the participant meets any conditions for early termination, such as adverse reactions or withdrawal of consent.

The expected length of participant involvement in the study is up to 52 weeks, corresponding to the maximum treatment period for the combination therapy. Conditions that may lead to early termination from the study include significant adverse events, non-compliance with study procedures, or voluntary withdrawal by the participant. The study aims to provide valuable insights into the real-life management of advanced clear-cell renal carcinoma through the integration of digital health technologies.

The clinical trial involves the administration of two experimental medications: **Nivolumab** and **Cabozantinib**. **Nivolumab**, marketed under the name OPDIVO, is provided as a 10 mg/mL concentrate for solution for infusion. It is a protein-based therapeutic agent, specifically classified as a monoclonal antibody. The pharmaceutical form is a solution for infusion, and it is administered intravenously. The maximum daily dose of Nivolumab is 240 mg, with a total maximum dose of 24,960 mg over a treatment period of up to 52 weeks. The administration schedule is determined by the study protocol, and compliance is monitored through regular assessments.

**Cabozantinib**, marketed as CABOMETYX, is available in the form of 40 mg film-coated tablets. It is a chemically synthesized compound, classified as a tyrosine kinase inhibitor. The route of administration is oral, with a maximum daily dose of 40 mg and a total maximum dose of 12,600 mg over a 52-week treatment period. The dosing schedule is outlined in the study protocol, and participant adherence is monitored through pill counts and patient diaries.

In this clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The study focuses on the combined administration of Nivolumab and Cabozantinib for the treatment of advanced clear-cell renal carcinoma. The trial aims to evaluate the impact of digital monitoring of self-reported symptoms to adjust treatment management during the first three months of the combined therapy. Compliance and adverse events are closely monitored to ensure participant safety and data integrity.

Efficacy in the clinical trial will be assessed through the primary endpoint, which involves the adjustment of treatment management based on weekly digital monitoring of patient-reported outcomes (PROs) using the Common Terminology Criteria for Adverse Events (CTCAEs). This includes any unplanned actions such as anticipated consultations, phone follow-ups, advice, treatment discontinuation, or hospitalization within the first three months of combined treatment with **cabozantinib** and **nivolumab** for advanced clear-cell renal carcinoma. The digital monitoring aims to evaluate the impact of self-reported symptoms on treatment management in a real-life setting. The trial will utilize digital tools to collect and analyze these patient-reported outcomes, ensuring timely adjustments to treatment plans as necessary. The study is designed to capture data continuously over the initial three-month period, allowing for a comprehensive assessment of treatment efficacy and management adjustments.