Treatment pause versus treatment continuation in good or intermediate risk with only one adverse prognostic factor in mRCC patients that has achieved an objective response at 12 months of treatment with PD-1/ PDL1 ICIs + VEGFR-Tyrosine Kinase Inhibitors (TKI) - SPICI

Phase 3

Active, not recruiting

Conditions: Metastatic renal cell carcinoma (mRCC) with a good or only one adverse prognostic factor intermediate risk per IMDC score

Registration Number: 2024-514644-93-00

Lead Sponsor: Centre Hospitalier Universitaire De Bordeaux

Brief Summary: To assess the non-inferiority of treatment pause compared to treatment continuation with PD-1/ PDL-L1 ICIs + VEGFR-Tyrosine Kinase inhibitor in an IMDC good risk or only one adverse prognostic factor intermediate risk mRCC population that has achieved an objective response between the end of the 11th month and the end of the 13th of treatment with the combination regimens

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.

Recruitment & Eligibility

Status: Ongoing, recruitment ended

Sex: Not specified

Target Recruitment: 372

Inclusion Criteria

Age ≥ 18 years at time of signing informed consent form

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

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 the 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

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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		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

Secondary Outcome Measures

Name	Time	Method
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		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
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)		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)
Mean scores in the Hospital Anxiety and Depression Scale at up to 12 months after randomisation		Mean scores in the Hospital Anxiety and Depression Scale at up to 12 months after randomisation
Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST)		Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST)
2-year overall survival		2-year overall survival
2-year progression-free survival		2-year progression-free survival
For patients in the experimental arm, site and distribution of the sites of progression: known lesions, new lesion(s) or both		For patients in the experimental arm, site and distribution of the sites of progression: known lesions, new lesion(s) or both
For patients in the experimental arm, distribution of treatment modality after progression: surveillance, focal treatment or general treatment		For patients in the experimental arm, distribution of treatment modality after progression: surveillance, focal treatment or general treatment
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		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
In France only, healthcare resource utilisation up to 12 months after randomisation, measured by medication use and hospitalisations		In France only, healthcare resource utilisation up to 12 months after randomisation, measured by medication use and hospitalisations

Trial Locations

Locations (24): Centre Hospitalier Regional Universitaire De Tours
🇫🇷
Tours, France
Centre De Lutte Contre Le Cancer Eugene Marquis
🇫🇷
Rennes Cedex, France
Assistance Publique Hopitaux De Paris
🇫🇷
Paris, France
Institut Gustave Roussy
🇫🇷
Villejuif Cedex, France
Centr Georges Francois Leclerc
🇫🇷
Dijon, France
Institut Regional Du Cancer De Montpellier
🇫🇷
Montpellier Cedex 5, France
Centre Hospitalier Universitaire De Bordeaux
🇫🇷
Bordeaux, France
Polyclinique De Limoges
🇫🇷
Limoges Cedex I, France
Centre Hospitalier Et Universitaire De Limoges
🇫🇷
Limoges Cedex 1, France
Centre Hospitalier Universitaire De Saint Etienne
🇫🇷
St Etienne Cedex 2, France
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Centre Hospitalier Regional Universitaire De Tours
🇫🇷Tours, France
Mathilde CANCEL
Site contact
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m.cancel@chu-tours.fr