CARE1: First Line Randomised Study Platform to Optimize Treatment in Patients with Metastatic Renal Cell Carcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Gustave Roussy

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

12 Apr 2024 → ongoing

Decision date (initial)

2024-11-25

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Efficacy

To compare the efficacy of immune checkpoint inhibitor combination (ICI-ICI) with nivolumab-ipilimumab (NIVO-IPI) versus ICI-VEGFR TKI combination in IMDC intermediate and poor risk patients with previously untreated mRCC based on PDL1 stratification. The efficacy will be compared in terms of overall survival for the PDL1(+) population and in terms of progression-free survival and overall survival (co-primary endpoints) for the PDL1(-) population.

Secondary objectives 9

1. Progression-free survival according to RECIST 1.1
2. Objective Response Rate according to RECIST 1.1
3. Quality of Life via questionnaires
4. Duration of Treatment
5. Time to treatment discontinuation
6. Treatment-free survival
7. Time to subsequent systemic anticancer therapy
8. Safety
9. Health Economic evaluation in France and the Netherlands only

Conditions and MedDRA coding

Metastatic renal cell carcinoma (mRCC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Histologically confirmed metastatic (AJCC Stage IV) renal cell carcinoma with a clear-cell component
2. Intermediate- or poor-risk mRCC as defined by IMDC classification.
3. Adult male or female patients (≥ 18 years of age at inclusion).
4. Karnofsky Performance Status (KPS) ≥70%.
5. Adequate organ and marrow function, according to investigator assessment and a.Absolute neutrophil count (ANC) ≥ 1000/μL (≥ 1.5 GI/L) b.Platelets ≥ 100,000/μL (≥ 100 GI/L) c.Hemoglobin ≥ 8 g/dL (≥ 80 g/L) d.Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 xULN. e.Calculated creatinine clearance ≥ 30 mL/min (≥ 0.67 mL/sec) using the CKD-EPI equation
6. Patient should understand, sign, and date the written informed consent form prior to anyprotocol-specific procedures performed
7. Patient should be able and willing to comply with study visits and procedures as per protocol
8. Patients must be affiliated to a social security system or beneficiary of the same
9. Female patients must either be of non-reproductive potential or must have a negativeserum pregnancy test within 14 days prior to the administration of study drug.Childbearing potential women must have agreed to use at least one highly effectivecontraceptive method during treatment on this trial and for up to 6 months after the lastdose of study treatment
10. Fertile men with a female partner of childbearing potential must agree to use malecondom plus spermicide. Also, it is recommended their women of childbearing potentialpartner use a highly effective method of contraception
11. Female subjects of childbearing potential must not be pregnant at screening

Exclusion criteria 7

1. Prior systemic anticancer therapy for mRCC including investigational agents. Note: One prior systemic adjuvant therapy is allowed for completely resected RCC and ifrecurrence occurred at least 6 months after the last dose of adjuvant therapy.
2. Uncontrolled brain metastases (adequately treated with radiotherapy and/orradiosurgery prior to randomization are eligible). Subjects who are neurologicallysymptomatic as a result of their CNS metastasis or are receiving systemic corticosteroidtreatment (prednisone equivalent > 10 mg/day) at the planned time of randomizationare not eligible
3. Concomitant oral anti-vitamin K anticoagulation. An exception is the use of LMWH ordirect oral anticoagulants (DOAC), if considered safe by investigator assessment
4. The subject has uncontrolled, significant intercurrent or recent illness such as thefollowing conditions: a.Cardiovascular i.Congestive heart failure (CHF) class III or IV as defined by the NewYork Heart Association, unstable angina pectoris, myocardialinfarction, serious cardiac arrhythmias (e.g., ventricular flutter,ventricular fibrillation, Torsades de pointes). ii.Uncontrolled hypertension despite optimal antihypertensive treatment. iii.Stroke, or other symptomatic ischemic event or severe thromboembolicevent (e.g., symptomatic pulmonary embolism [PE], incidental PE isacceptable if deemed safe by the investigator) within 3 months beforerandomization. b.Active GI bleeding or symptomatic Gastrointestinal (GI) tract obstruction c.Clinically significant bleeding including uncontrolled hematuria, hematemesis,or hemoptysis d.Autoimmune disease that has been symptomatic or requiredimmunosuppressive systemic treatment within the past two years from the dateof randomization. Note: Patients with a history of Crohn’s disease or ulcerative colitis are always excluded e.Any condition requiring systemic treatment with either corticosteroids (> 10 mgdaily prednisone equivalent) or other immunosuppressive medications within14 days of randomization. Note: Inhaled, intranasal, intra-articular, or topical steroids are permitted.Adrenal replacement steroid doses > 10 mg daily prednisone equivalent arepermitted. Transient short-term use of systemic corticosteroids for allergicconditions (e.g., contrast allergy) is also allowed. f.Active infection requiring systemic treatment. g.Major surgery (e.g., nephrectomy, GI surgery, removal of brain metastasis)within 4 weeks prior to randomization or serious non-healing wound/ulcer/bonefracture. disorders
5. Pregnant or breastfeeding females.
6. Any other active malignancy at time of randomization or diagnosis of anothermalignancy within 3 years prior to randomization that requires active treatment, exceptfor locally curable cancers that have been apparently cured
7. Persons deprived of their freedom or under guardianship, or for whom it would be impossible to undergo the medical follow-up required by the trial, for geographic, socialor psychological reasons

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

1. Overall Survival (OS)
2. Progression-free survival according to RECIST 1.1 NB: Progression-free survival is a co-primary endpoint in the PDL1(-) population
3. Objective Response Rate (ORR) according to RECIST 1.1
4. Percentage of patients experiencing a deterioration of ≥3 points on the NFKSI-19 scorein the first twelve months after randomization; Mean Change from Baseline in EQ-VAS andResponse frequencies for the EQ-5D-5L dimensions
5. Median treatment duration (per treatment)
6. Time to subsequent systemic therapy, defined as the time from the date ofrandomisation to the date of next subsequent systemic therapy. In absence of subsequenttherapy, the data will be censored at the date of last follow-up; Patients dying without receivinga subsequent treatment will be censored at the date of death.
7. Percentage of subjects experiencing grade 3-5 AEs, percentage of patientsexperiencing treatment-related grade 3-5 AEs, Percentage of patients experiencing AE grade≥2leading to the modification of administration of a study drug
8. Health economic evaluation through the incremental cost per Quality-adjusted life year(QALY), incremental net monetary benefit in the two patient subgroups (PDL1(+) and PDL1(-)respectively)

Investigational products

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

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Gustave Roussy

Sponsor organisation

Institut Gustave Roussy

Address

114 Rue Edouard Vaillant

City

Villejuif

Postcode

94800

Country

France

Scientific contact point

Organisation

Institut Gustave Roussy

Contact name

Benjamin Besse

Public contact point

Organisation

Institut Gustave Roussy

Contact name

Benjamin Besse

Locations

10 EU/EEA countries · 121 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 36 files

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

Application history

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