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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05219318
Other study ID # CHUBX 2021/08
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date January 23, 2023
Est. completion date January 2025

Study information

Verified date March 2023
Source University Hospital, Bordeaux
Contact Marine GROSS-GOUPIL, MD PhD
Phone (0)5 56 79 58 08
Email marine.gross-goupil@chu-bordeaux.fr
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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 at 12 months 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.


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 12 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.


Recruitment information / eligibility

Status Recruiting
Enrollment 372
Est. completion date January 2025
Est. primary completion date January 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 in the last 12 months for 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) after 12 months 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 - 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: - Any active central nervous system (CNS) metastases - 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

Study Design


Intervention

Drug:
Combination PD-1/PD-L1 ICI + VEGFR-TKI
The study will enroll patients achieving an objective response after 12 months of treatment with the combination PD-1/PD-L1 ICI + VEGFR-TKI as recommended in the Summary of Product Characteristics (SmPC)
Other:
Treatment pause
Combination regimens discontinuation until progression with the possibility to resume initial combination regimens at progression

Locations

Country Name City State
France CH de la Cote Basque - Service d'Oncologie Bayonne
France CHU de Besançon - Service d'Oncologie Besançon
France CHU de Bordeaux - Service d'Oncologie Bordeaux
France Centre François Baclesse - Service d'Oncologie Caen
France Centre Jean Perrin - Service d'Oncologie Clermont-Ferrand
France AP-HP - Henri Mondor - Service d'Oncologie Créteil
France Centre Georges-François Leclerc - Service d'Oncologie Dijon
France CHU Grenoble Alpes - Service d'Oncologie Grenoble
France CHU de Limoges - Service d'Oncologie Limoges
France Polyclinique de Limoges - Service d'Oncologie Limoges
France Centre Leon Berard - Service d'Oncologie Lyon
France Hospices Civils de Lyon - Service d'Oncologie Lyon
France Institut Paoli-Calmettes - Service d'Oncologie Marseille
France Institut Régional du Cancer - Service d'Oncologie Montpellier
France Centre Antoine Lacassagne - Service d'Oncologie Nice
France AP-HP - Hôpital Européen Georges Pompidou - Service d'Oncologie Paris
France AP-HP - Hôpital Saint Louis - Service d'Oncologie Paris
France CHU de Poitiers - Service d'Oncologie Poitiers
France Centre Eugène Marquis - Service d'Oncologie Rennes
France CHU de Saint-Etienne - Service d'Oncologie Saint-Étienne
France CHU de la Réunion Site Sud - Service d'Oncologie Saint-Pierre
France Institut de cancérologie Strasbourg Europe - Service d'Oncologie Strasbourg
France Hopital Foch - Service d'Oncologie Suresnes
France IUCT Oncopole - Service d'Oncologie Toulouse
France CHU de Tours - Service d'Oncologie Tours
France Institut de Cancérologie de Lorraine - Service d'Oncologie vandoeuvre les Nancy
France Institut Gustave Roussy - Service d'Oncologie Villejuif

Sponsors (1)

Lead Sponsor Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary Proportion of participants without progression 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 Up to 12 months after randomisation
Secondary Overall safety profile and tolerability event 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 Up to 12 months after randomisation
Secondary Overall survival (OS) OS is defined as the time between the date of randomisation and the date of death due to any cause From randomisation until 2 years of follow-up
Secondary Progression-free survival (PFS) 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 From randomisation until 2 years of follow-up
Secondary Mean change in quality of life 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 Up to 12 months after randomisation
Secondary Quality-adjusted survival 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 Up to 12 months after randomisation
Secondary Anxiety and depression Mean scores in the Hospital Anxiety and Depression Scale at up to 12 months after randomisation Up to 12 months after randomisation
Secondary Site and distribution of the sites of progression: known lesions, new lesion(s) or both From randomisation until 2 years of follow-up
Secondary Distribution of treatment modality after progression Proportion of participants treated after progression with surveillance, focal treatment or general treatment From randomisation until 2 years of follow-up
Secondary 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
Secondary Healthcare resource utilisation 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 Up to 12 months after randomisation
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