Locally advanced or metastatic papillary cell carcinoma (PRCC) MedDRA version: 21.1 Level: PT Classification code 10050513 Term: Metastatic renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Inlyta (axitinib)
Product Name: AXITINIB
Product Code: AG-013736
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: AXITINIB
CAS Number: 319460-85-0
Current Sponsor code: AG-013
Sponsors
CENTRE LEON BERARD
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: I1. Age = 18 years on the day of signing informed consent. I2. Metastatic or locally advanced (inoperable) type 2 or mixed PRCC, histologically confirmed by central review: FFPE blocks (or all HES and IHC slides) with the initial histology report must be sent for central reading before confirmation of inclusion in the study. I3. No prior systemic treatment for renal cancer (chemotherapy, immunotherapy, anti-angiogenic drugs, or treatment under evaluation) even in adjuvant setting. I4. At least one measurable site of disease according to RECIST v1.1. I5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) = 1 evaluated within 7 days prior to the date of inclusion. I6. In case of prior radiation therapy, discontinuation of irradiation for at least 3 weeks before first dose of study treatment, with at least 1 site kept/preserved for evaluation. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (= 2 weeks - limited field (1.5 × ULN), I8. Absence of significant proteinuria (=65 years) yes F.1.3.1 Number of subjects for this age range 36
Exclusion criteria
Exclusion criteria: NI1. Presence of brain metastases on Magnetic Resonance Imaging (MRI) or Computed Tomography-scan (CT-scan) performed within 28 days prior to inclusion. Patients with a history of brain metastases treated by surgery or stereotactic surgery, with normal brain MRI or CT-scan are allowed to participate. NI2. Metastases with high risk of nervous compression or bone lesion with high risk of fracture. NI3. Prior history of other malignancies other than PRCC (except for curatively treated basal cell or squamous cell carcinoma of the skin or in situ uterine cervix carcinoma) unless the subjects has been free of the disease for at least 5 years. NI4. Major surgical procedure, open biopsy, or serious none healing wound within 28 days prior to inclusion. NI5. Significant cardiovascular disease, including: - Disorder of left ventricular function with a left ventricular ejection fraction (LVEF) < 50%, - Uncontrolled arterial hypertension under adapted medication: systolic blood pressure = 150 mmHg or diastolic blood pressure = 90 mmHg or both despite appropriate therapy, blood pressure must be monitored and controlled before inclusion, or patients under 3 antihypertensive therapies at screening, - Myocardial infarction, severe angina, or unstable angina within 6 months prior to inclusion, - History of serious ventricular arrhythmia (ie ventricular tachycardia or ventricular fibrillation), - Cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication), - Coronary or peripheral artery bypass graft or active coronary stent within 6 months prior to inclusion, - Veinous thrombosis or pulmonary embolism within 6 months prior to inclusion. NI6. Any anti-coagulation therapy except prophylactic low dose. NI7. History of auto-immune disease except thyroiditis more than 6 months ago. NI8. History of any allograft. NI9. HIV, HBV, HCV active infections. NI10. Any active acute or chronic or uncontrolled infection/disorder that would impair the ability to evaluate the patient or the ability for the patient to complete the study. NI11. Known history of active TB (Bacillus Tuberculosis). NI12. Interstitial lung disease, respiratory insuffisancy whatever the cause. NI13. Prior (non-infectious) pneumonitis requiring systemic corticosteroid therapy or current pneumonitis. NI14. Inability to swallow oral medications, or presence of active inflammatory bowel disease, partial or complete bowel obstruction or chronic diarrhea. NI15. History of severe hypersensitivity to another monoclonal antibody. NI16. Known hypersensitivity to the active substances or to any of the excipients. NI17. Receiving or having received immunosuppressive therapy or corticosteroids within 1 month prior to inclusion (except for hydrocortisone for substitution purposes). NI18. Live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. COVID-19 vaccine is allowed if non-living/inactivated. NI19. Psychological, familial, sociological, or geographical conditions that would limit compl
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the efficacy of axitinib + pembrolizumab versus axitinib in metastatic patients with type 2 papillary renal carcinoma in first-line treatment. ;Secondary Objective: To evaluate in each arm: - The duration of response (DOR), - The best overall response (BOR) using RECIST 1.1 , - The progression-free survival (PFS), - The overall survival (OS), - The safety according to NCI CTC-AE v5. ;Primary end point(s): objective response rate (ORR );Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate in each arm: - The duration of response (DOR) - The best overall response (BOR), - The progression-free survival (PFS), - The overall survival (OS), - The safety according to NCI CTC-AE v5.;Timepoint(s) of evaluation of this end point: • DOR, calculated from the date of first documented response (CR or PR) to the date of first documented progression or death. It applies only to patients whose BOR is either SR or PR. • BOR, defined as the best response according to RECIST v1.1 recorded from the baseline until the end of the study (treatment). • PFS, defined as the time from the date of first treatment administration to the date of documented progression or death from any cause. • OS, defined as the time from the date of first treatment administration to the date of death from any cause. • Safety profile, determined using the National Cancer Institute – Common Terminology Criteria for Adverse Event (NCI-CTC AE) grading scale version 5.0. Adverse events will be described by their intensity and severity. | — |
Countries
France
Contacts
Public ContactDRCI
CENTRE LEON BERARD
Outcome results
None listed