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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Bordeaux

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Dec 2022 → ongoing

Decision date (initial)

2024-07-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514644-93-00

EudraCT number

2021-003447-25

ClinicalTrials.gov

NCT05219318

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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

Secondary objectives 8

1. To compare between treatment pause and treatment continuation the overall safety profile
2. To compare between treatment pause and treatment continuation the health-related quality of life
3. To compare between treatment pause and treatment continuation the anxiety and depression
4. To compare between treatment pause and treatment continuation 2-year overall survival and progression-free survival
5. To describe the modalities of progression (site, known lesions, or new lesions or both) for patients in the experimental arm
6. To describe the therapeutic modalities at progression for patients in the experimental arm
7. To describe the oncological outcomes when restarting PD-1/ PD-L1 ICI + VEGFR-TKI in the event of progression for patients in the experimental arm
8. (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

Conditions and MedDRA coding

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

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Age ≥ 18 years at time of signing informed consent form
2. Signed informed consent form
3. Histological confirmation of RCC with a Clear-cell component, including subject who also have a sarcomatoïd feature
4. Advanced (not amenable to curative surgery or radiation therapy) or Metastatic RCC (American Joint Committee on Cancer [AJCC] Stage IV)
5. Participants with good or intermediate risk with only one adverse prognostic factor will be eligible as per International Metastatic RCC Database Consortium (IMDC) criteria
6. Prior first line therapy for mRCC with the combination of PD-1/ PD-L1 ICI plus VEGFR-TKI
7. 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
8. 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
9. CT scan at the initiation of this treatment must be available
10. Karnofsky Performance Status (KPS) grade ≥ 70%
11. 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
12. Adequate organ function
13. 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
14. Sexually active male patients must agree to use condoms and continue its use for 5 months after the last PD1/PD L1 ICI administration
15. Willingness and ability to comply with study procedures
16. Patient affiliated to a social security system or benefit from the same system

Exclusion criteria 8

1. Prior therapy with PD-1/PD-L1 ICI or VEGFR-TKI monotherapy
2. Poorly controlled hypertension despite antihypertensive therapy
3. More than one adverse prognostic factor (IMDC criteria)
4. Women who are pregnant or lactating
5. Current participation in an investigational program
6. Patient with any medical or psychiatric condition or disease, which would make the patient inappropriate for entry into this study
7. Adults who are the subject of legal protection measures
8. Persons deprived of their liberty by a judicial or administrative decision

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 10

1. 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
2. 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)
3. Mean scores in the Hospital Anxiety and Depression Scale at up to 12 months after randomisation
4. Quality-adjusted time without symptoms of disease or toxicity (Q-TWiST)
5. 2-year overall survival
6. 2-year progression-free survival
7. For patients in the experimental arm, site and distribution of the sites of progression: known lesions, new lesion(s) or both
8. For patients in the experimental arm, distribution of treatment modality after progression: surveillance, focal treatment or general treatment
9. 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
10. In France only, healthcare resource utilisation up to 12 months after randomisation, measured by medication use and hospitalisations

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Bordeaux

Sponsor organisation

Centre Hospitalier Universitaire De Bordeaux

Address

12 Rue Dubernat, Cs 91286 Cs 91286

City

Talence

Postcode

33400

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Bordeaux

Contact name

Coordinating Investigator

Public contact point

Organisation

Centre Hospitalier Universitaire De Bordeaux

Contact name

Coordinating Investigator

Locations

1 EU/EEA country · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications