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

Metastatic Renal Cell Carcinoma Clinical Trial

— SPICI  

Official title:

SPICI: Strategic Treatment Pause of First-line Immune Check Point Inhibitor + VEGFR-Tyrosine Kinase Inhibitor in Good or Only One Adverse Prognostic Factor in Intermediate Risk Metastatic Renal Cell Carcinoma (mRCC) With an Objective Response: a Randomised, Non-inferiority Phase III Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05219318
• Other study ID #: CHUBX 2021/08
• Status: Recruiting
• Phase: Phase 3
• 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
• 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Metastatic Renal Cell Carcinoma

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