Good or Only One Adverse Prognostic Factor Intermediate Risk Per IMDC Score, Metastatic Renal Cell Carcinoma
Conditions
Keywords
Metastatic renal cell carcinoma (mRCC), Objective response, Treatment pause, Treatment continuation
Brief summary
The purpose of this study is to demonstrate the non-inferiority of treatment pause versus treatment continuation in good or intermediate risk with only one adverse prognostic factor as per IMDC mRCC patients with a confirmed objective response between the end of the 11th month to th end of the 13th month of treatment with PD-1/PD-L1 ICI plus VEGFR-TKI. Tolerance and quality of life of treatment pause with PD-1/PD-L1 ICI + VEGFR-TKI compared to treatment continuation will be reported. In France, its impact on healthcare resource utilization will also be assessed.
Detailed description
Although multiple combinations therapies in particular PD-1/PD-L1 immune-checkpoint inhibitors (PD-1/PD-L1 ICIs) in combination with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) are approved and have improved patient's outcomes with mRCC, they are maintained until disease progression and treatment pause after an objective response has not been fully explored \[5-7\]. The good-risk population is characterised by prolonged survival therefore a treatment pause in this population could impact the quality of life, safety and total cost of care, without impacting outcome. As well, intermediate risk population group is heterogeneous, while the one's with only one adverse prognostic factor seems to be closed to the outcome of good risk population \[11-15\]. As the purpose of the study is to target patients with an objective response, there is already a selection of patients with a better outcome. Patient will be randomised after 11 to 13 months of treatment with PD-1/PD-L1 ICI plus VEGFR-TKI (treatment pause versus treatment continuation) and follow every 3 months for a period of 12 months following by 12 additional months for survival follow-up.
Interventions
DRUGCombination PD-1/PD-L1 ICI + VEGFR-TKI
The study will enroll patients achieving an objective response beween the end of the 11th month and the end of the 13th month of treatment with the combination PD-1/PD-L1 ICI + VEGFR-TKI as recommended in the Summary of Product Characteristics (SmPC)
OTHERTreatment pause
Combination regimens discontinuation until progression with the possibility to resume initial combination regimens at progression
Sponsors
University Hospital, Bordeaux
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years at time of signing informed consent form * Signed informed consent form * Histological confirmation of RCC with a Clear-cell component, including subject who also have a sarcomatoïd feature * Advanced (not amenable to curative surgery or radiation therapy) or Metastatic RCC (American Joint Committee on Cancer \[AJCC\] Stage IV) * Participants with good or intermediate risk with only one adverse prognostic factor will be eligible as per International Metastatic RCC Database Consortium (IMDC) criteria * Prior first line therapy for mRCC with the combination of PD-1/ PD-L1 ICI plus VEGFR-TKI * 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 * Patients with an objective response (complete response or partial response) between the end of 11th month and the end of the 13th month of the combination treatment with PD-1/PD-L1 ICI and VEGFR-TKI. CT scan at the initiation of this treatment must be available. * Karnofsky Performance Status (KPS) grade ≥ 70% * 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 * Adequate organ function * 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. * Sexually active male patients must agree to use condoms and continue its use for 5 months after the last PD1/PD L1 ICI administration. * Willingness and ability to comply with study procedures. * Patient affiliated to a social security system or benefit from the same system
Exclusion criteria
* Prior therapy with PD-1/PD-L1 ICI or VEGFR-TKI monotherapy. * Poorly controlled hypertension despite antihypertensive therapy * More than one adverse prognostic factor (IMDC criteria) * Women who are pregnant or lactating; * Current participation in an investigational program * Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study * Adults who are the subject of legal protection measures * Persons deprived of their liberty by a judicial or administrative decision
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants without progression | Up to 12 months after randomisation | Disease progression at up to 12 months after randomisation will be based on a blinded independent central review (BICR) according to RECIST v1.1 criteria, with tumor assessment performed every 12 weeks during study participation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | From randomisation until 2 years of follow-up | OS is defined as the time between the date of randomisation and the date of death due to any cause |
| Progression-free survival (PFS) | From randomisation until 2 years of follow-up | PFS is defined as the time between date of randomisation and the first date of the documented disease progression, or death due to any cause, whichever occurs first |
| Mean change in quality of life | Up to 12 months after randomisation | Measured by the NCCN functional assessment of cancer therapy-kidney symptom index (FKSI-19). The NCCN FKSI-19 is a 19-item scale that measures tumor specific health-related quality of life in kidney cancer participants. A higher score indicates fewer symptoms |
| Quality-adjusted survival | Up to 12 months after randomisation | The quality-adjusted time without symptoms or toxicity (Q-TWiST) is a simultaneous assessment of time without toxicity or disease progression, which essentially examines the trade-off between AEs and treatment benefits |
| Overall safety profile and tolerability event | Up to 12 months after randomisation | 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 |
| Site and distribution of the sites of progression: known lesions, new lesion(s) or both | From randomisation until 2 years of follow-up | — |
| Distribution of treatment modality after progression | From randomisation until 2 years of follow-up | Proportion of participants treated after progression with surveillance, focal treatment or general treatment |
| Percentage of patients with status SD or in objective response at 6 months after restarting PD-1/PD-L1 ICI + VEGFR-TKI | From randomisation until 2 years of follow-up | — |
| Healthcare resource utilisation | Up to 12 months after randomisation | Costs of care will be estimated in the perspective of the French Healthcare System over a 12-month times horizon. Conventional tariffs of hospitalizations will be used to calculate costs |
| Anxiety and depression | Up to 12 months after randomisation | Mean scores in the Hospital Anxiety and Depression Scale at up to 12 months after randomisation |
Countries
France
Outcome results
None listed