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/ PD-L1 ICIs + VEGFR-Tyrosine Kinase Inhibitors (TKI)

Strategic treatment Pause of first-line Immune Check point Inhibitor + VEGFR-Tyrosine Kinase Inhibitor in good or intermediate risk with only one adverse prognostic factor in metastatic renal cell carcinoma (mRCC) patients with an objective response: a randomised, non-inferiority phase III study - SPICI

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2021-003447-25-FR

Enrollment

372

Registered

2021-10-05

Start date

2021-12-01

Completion date

Unknown

Last updated

2024-09-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Interventions

Trade Name: INLYTA Product Name: AXITINIB Pharmaceutical Form: Coated tablet Trade Name: KEYTRUDA Product Name: PENBROLIZUMAB Pharmaceutical Form: Solvent for solution for infusion

Eligibility

Sex/Gender

All

Inclusion 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 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 111 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 75

Exclusion criteria

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

Design outcomes

Primary

Measure	Time frame
Main Objective: To demonstrate the non-inferiority of treatment pause compared to treatment continuation with PD-1/ PD-L1 ICI +VEGFR-TKI in an IMDC good or intermediate risk with only one adverse prognostic factor in mRCC population that has achieved an objective response at 12 months of treatment with the combination regimens;Secondary Objective: To compare between treatment pause (experimental arm) and treatment continuation (control arm): •The overall safety and tolerability •The health-related quality of life •The anxiety and depression •The quality-adjusted survival, •2-year overall survival and progression-free survival. To describe the following for patients in the experimental arm: •the modalities of progression (site, known lesions, or new lesions or both) •the therapeutic modalities at progression •the oncological outcomes when restarting PD-1/ PD-L1 ICI + VEGFR-TKI in the event of progression (In France only) To compare healthcare resource utilization and costs at 12 months between treatment pause (experimental arm) and treatment continuation (control arm). Costs will be estimated in the perspective of the French Healthcare System.;Primary end point(s): Proportion 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 ;Timepoint(s) of evaluation of this end point: At up to 12 months after randomisation	—

Measure

Time frame

Main Objective: To demonstrate the non-inferiority of treatment pause compared to treatment continuation with PD-1/ PD-L1 ICI +VEGFR-TKI in an IMDC good or intermediate risk with only one adverse prognostic factor in mRCC population that has achieved an objective response at 12 months of treatment with the combination regimens;Secondary Objective: To compare between treatment pause (experimental arm) and treatment continuation (control arm): •The overall safety and tolerability •The health-related quality of life •The anxiety and depression •The quality-adjusted survival, •2-year overall survival and progression-free survival. To describe the following for patients in the experimental arm: •the modalities of progression (site, known lesions, or new lesions or both) •the therapeutic modalities at progression •the oncological outcomes when restarting PD-1/ PD-L1 ICI + VEGFR-TKI in the event of progression (In France only) To compare healthcare resource utilization and costs at 12 months between treatment pause (experimental arm) and treatment continuation (control arm). Costs will be estimated in the perspective of the French Healthcare System.;Primary end point(s): Proportion 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 ;Timepoint(s) of evaluation of this end point: At up to 12 months after randomisation

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Secondary

Measure	Time frame
Secondary end point(s): • 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 NCCN 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 • Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) For patients in the experimental arm: • Site and distribution of the sites of progression: known lesions, new lesion(s) or both • Distribution of treatment modality after progression: surveillance, focal treatment or general treatment • 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. • Costs of care will be estimated in the perspective of the French Healthcare System over a 12-month times horizon. Conventional tariffs of medication and hospitalizations will be used to calculate costs.;Timepoint(s) of evaluation of this end point: Up to 12 months after randomisation	—

Measure

Time frame

Secondary end point(s): • 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 NCCN 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 • Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) For patients in the experimental arm: • Site and distribution of the sites of progression: known lesions, new lesion(s) or both • Distribution of treatment modality after progression: surveillance, focal treatment or general treatment • 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. • Costs of care will be estimated in the perspective of the French Healthcare System over a 12-month times horizon. Conventional tariffs of medication and hospitalizations will be used to calculate costs.;Timepoint(s) of evaluation of this end point: Up to 12 months after randomisation

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Countries

France

Contacts

Public ContactSophie TABUTEAU

CHU DE BORDEAUX

sophie.tabuteau@chu-bordeaux.fr33557821066

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026