PEMBROLIZUMAB for Metastatic renal cell carcinoma

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years at time of signing informed consent form\n- Karnofsky Performance Status (KPS) grade ≥ 70%\n- Measurable disease as per RECIST v1.1 per investigator on CT scan at the initiation of first line treatment with combination treatment with PD-1/PD-L1 ICI and VEGFR-TKI\n- Adequate organ function\n- Females of childbearing potential must use a highly effective contraception (combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral ; intravaginal ;transdermal) ; progestogen-only hormonal contraception associated with inhibition of ovulation (oral ; injectable ; implantable ; intrauterine device (IUD) ; intrauterine hormone-releasing system ( IUS)) ; bilateral tubal occlusion ; vasectomised partner ; sexual abstinence) and continue its use for 5 months after the last PD1/PD L1 ICI administration\n- Sexually active male patients must agree to use condoms and continue its use for 5 months after the last PD1/PD L1 ICI administration\n- Willingness and ability to comply with study procedures\n- Patient affiliated to a social security system or benefit from the same system\n- Signed informed consent form\n- Histological confirmation of RCC with a Clear-cell component, including subject who also have a sarcomatoïd feature\n- Advanced (not amenable to curative surgery or radiation therapy) or Metastatic RCC (American Joint Committee on Cancer [AJCC] Stage IV)\n- Participants with good or intermediate risk with only one adverse prognostic factor will be eligible as per International Metastatic RCC Database Consortium (IMDC) criteria\n- Prior first line therapy for mRCC with the combination of PD-1/ PD-L1 ICI plus VEGFR-TKI\n- First line treatment with the combination of PD-1/PD-L1 ICI and VEGFR-TKI must be ongoing whatever the dose with no period of discontinuation > 6 consecutive weeks during treatment of the PD-1/PD-L1 ICI, and 2 consecutive weeks in the last 3 months before randomisation for the VEGFR-TKI\n- Patients with an objective response (complete response or partial response) between the end of the 11th month and the end of the 13th month of the combination treatment with PD-1/PD-L1 ICI and VEGFR-TKI\n- CT scan at the initiation of this treatment must be available"}

Exclusion criteria

• {"criterion_text":"- Prior therapy with PD-1/PD-L1 ICI or VEGFR-TKI monotherapy\n- Poorly controlled hypertension despite antihypertensive therapy\n- More than one adverse prognostic factor (IMDC criteria)\n- Women who are pregnant or lactating\n- Current participation in an investigational program\n- Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study\n- Adults who are the subject of legal protection measures\n- Persons deprived of their liberty by a judicial or administrative decision"}

Primary endpoints

• {"endpoint_text":"- Percentage of participants without progression at up to 12 months after randomisation, based on a blinded independent central review (BICR) according to RECIST v1.1 criteria","definition_or_measurement_approach":"Proportion of participants without progression up to 12 months post-randomisation assessed by blinded independent central review according to RECIST v1.1."}

Secondary endpoints

• {"endpoint_text":"- Proportion of participants who experience an adverse event or serious adverse event, and mean number of adverse events or serious adverse events up to 12 months after randomisation","definition_or_measurement_approach":"Proportion and mean number of AEs/SAEs occurring up to 12 months after randomisation (safety monitoring)."}
• {"endpoint_text":"- Mean change in quality of life up to 12 months after randomisation, measured by the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI-19)","definition_or_measurement_approach":"Change from baseline in FKSI-19 scores up to 12 months after randomisation."}
• {"endpoint_text":"- Mean scores in the Hospital Anxiety and Depression Scale at up to 12 months after randomisation","definition_or_measurement_approach":"Mean HADS scores up to 12 months post-randomisation."}
• {"endpoint_text":"- Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST)","definition_or_measurement_approach":"Q-TWiST calculated as quality-adjusted time without symptoms or toxicity (methodology referenced but not further specified in the record)."}
• {"endpoint_text":"- 2-year overall survival","definition_or_measurement_approach":"Defined as time from randomisation to date of death from any cause (2-year OS)."}
• {"endpoint_text":"- 2-year progression-free survival","definition_or_measurement_approach":"Defined as time from randomisation to documented disease progression or death, whichever occurs first (2-year PFS)."}
• {"endpoint_text":"- For patients in the experimental arm, site and distribution of the sites of progression: known lesions, new lesion(s) or both","definition_or_measurement_approach":"Descriptive assessment of progression sites (known lesions, new lesions, or both) for experimental-arm patients."}
• {"endpoint_text":"- For patients in the experimental arm, distribution of treatment modality after progression: surveillance, focal treatment or general treatment","definition_or_measurement_approach":"Descriptive distribution of post-progression therapeutic modalities (surveillance, focal, general) in experimental arm."}
• {"endpoint_text":"- For patients in the experimental arm, if general treatment when restarting PD-1/PD-L1 ICI + VEGFR-TKI, percentage of patients with status SD or in objective response at 6 months","definition_or_measurement_approach":"Percentage of experimental-arm patients who, after restarting PD-1/PD-L1 ICI + VEGFR-TKI, have stable disease or objective response at 6 months."}
• {"endpoint_text":"- In France only, healthcare resource utilisation up to 12 months after randomisation, measured by medication use and hospitalisations","definition_or_measurement_approach":"Country-specific (France) health resource utilisation over 12 months measured via medication use and hospitalisations; costs estimated from French Healthcare System perspective."}

France

Earliest CTIS Part Ii Submission Date

16-07-2024

Latest Decision Or Authorization Date

27-05-2025

Processing Time Days

315

Number Of Sites

26

Number Of Participants

372

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Bordeaux

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France