Treatment Pause Versus Treatment Continuation in IMDC Good or Intermediate Risk With Only One Adverse Prognostic Factor in mRCC Patients With an Objective Response at 12 Months of Treatment With PD1/ PDL1 ICIs + VEGFR-Tyrosine Kinase Inhibitors

NCT ID: NCT05219318

Last Updated: 2025-06-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-23
• Study Completion Date: 2027-01-31

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.

Conditions

Metastatic Renal Cell Carcinoma; Good or Only One Adverse Prognostic Factor Intermediate Risk Per IMDC Score

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment pause

Treatment pause for 12 months

Group Type: EXPERIMENTAL

Treatment pause

Intervention Type: OTHER

Combination regimens discontinuation until progression with the possibility to resume initial combination regimens at progression

Treatment continuation

Treatment continuation regimens with PD-1/PD-L1 ICI + VEGFR-TKI until disease progression or unacceptable toxicity

Group Type: ACTIVE_COMPARATOR

Combination PD-1/PD-L1 ICI + VEGFR-TKI

Intervention Type: DRUG

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)

Interventions

Combination 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)

Intervention Type: DRUG

Treatment pause

Combination regimens discontinuation until progression with the possibility to resume initial combination regimens at progression

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Bordeaux

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marine GROSS-GOUPIL, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bordeaux

Locations

CH de la Cote Basque - Service d'Oncologie

Bayonne, , 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-Etienne, , 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

Vandœuvre-lès-Nancy, , France

Institut Gustave Roussy - Service d'Oncologie

Villejuif, , France

Countries

France

Other Identifiers

CHUBX 2021/08

Identifier Type: -

Identifier Source: org_study_id