Clinical trial NCT05219318: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Metastatic Renal Cell Carcinoma
Good or Only One Adverse Prognostic Factor Intermediate Risk Per IMDC Score
Keywords: Metastatic renal cell carcinoma (mRCC)
Objective response
Treatment pause
Treatment continuation
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2022-02-02
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Proportion of participants without progression
timeFrame: Up to 12 months after randomisation
Secondary outcomes:
measure: Overall safety profile and tolerability event
timeFrame: Up to 12 months after randomisation
measure: Overall survival (OS)
timeFrame: From randomisation until 2 years of follow-up
measure: Progression-free survival (PFS)
timeFrame: From randomisation until 2 years of follow-up
measure: Mean change in quality of life
timeFrame: Up to 12 months after randomisation
measure: Quality-adjusted survival
timeFrame: Up to 12 months after randomisation
measure: Anxiety and depression
timeFrame: Up to 12 months after randomisation
measure: Site and distribution of the sites of progression: known lesions, new lesion(s) or both
timeFrame: From randomisation until 2 years of follow-up
measure: Distribution of treatment modality after progression
timeFrame: From randomisation until 2 years of follow-up
measure: Percentage of patients with status SD or in objective response at 6 months after restarting PD-1/PD-L1 ICI + VEGFR-TKI
timeFrame: From randomisation until 2 years of follow-up
measure: Healthcare resource utilisation
timeFrame: Up to 12 months after randomisation
Other outcomes:
Locations:
city: Bayonne
country: France
facility: CH de la Cote Basque - Service d'Oncologie
city: Bordeaux
country: France
facility: CHU de Bordeaux - Service d'Oncologie
city: Caen
country: France
facility: Centre François Baclesse - Service d'Oncologie
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin - Service d'Oncologie
city: Créteil
country: France
facility: AP-HP - Henri Mondor - Service d'Oncologie
city: Dijon
country: France
facility: Centre Georges-François Leclerc - Service d'Oncologie
city: Grenoble
country: France
facility: CHU Grenoble Alpes - Service d'Oncologie
city: Limoges
country: France
facility: CHU de Limoges - Service d'Oncologie
city: Limoges
country: France
facility: Polyclinique de Limoges - Service d'Oncologie
city: Lyon
country: France
facility: Centre Leon Berard - Service d'Oncologie
city: Lyon
country: France
facility: Hospices Civils de Lyon - Service d'Oncologie
city: Marseille
country: France
facility: Institut Paoli-Calmettes - Service d'Oncologie
city: Montpellier
country: France
facility: Institut Régional du Cancer - Service d'Oncologie
city: Nice
country: France
facility: Centre Antoine Lacassagne - Service d'Oncologie
city: Paris
country: France
facility: AP-HP - Hôpital Européen Georges Pompidou - Service d'Oncologie
city: Paris
country: France
facility: AP-HP - Hôpital Saint Louis - Service d'Oncologie
city: Poitiers
country: France
facility: CHU de Poitiers - Service d'Oncologie
city: Rennes
country: France
facility: Centre Eugène Marquis - Service d'Oncologie
city: Saint-Pierre
country: France
facility: CHU de la Réunion Site Sud - Service d'Oncologie
city: Saint-Étienne
country: France
facility: CHU de Saint-Etienne - Service d'Oncologie
city: Strasbourg
country: France
facility: Institut de cancérologie Strasbourg Europe - Service d'Oncologie
city: Suresnes
country: France
facility: Hopital Foch - Service d'Oncologie
city: Toulouse
country: France
facility: IUCT Oncopole - Service d'Oncologie
city: Tours
country: France
facility: CHU de Tours - Service d'Oncologie
city: vandoeuvre les Nancy
country: France
facility: Institut de Cancérologie de Lorraine - Service d'Oncologie
city: Villejuif
country: France
facility: Institut Gustave Roussy - Service d'Oncologie
Study officials:
affiliation: University Hospital, Bordeaux
name: Marine GROSS-GOUPIL, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: