Clinical trial NCT02489695 (phase 2, status: completed)
Conditions: papillary renal cell carcinoma
ICD codes: C22.0, C4A.9, C7B.1, C4A.0, C4A.31, C4A.51, C4A.8
Drugs: axitinib
SMILES: [H][N]([H])([H])[Pt](Cl)(Cl)[N]([H])([H])[H]
Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥ 18 years.

          2. Metastatic or locally advanced (inoperable) pure type 1 or 2 or mixed PRCC,
             histologically confirmed by central review: relevant slides [and blocks if available]
             with the initial histology report must be sent for central reading before confirmation
             of inclusion.

          3. No prior systemic treatment for metastatic renal cancer (chemotherapy, immunotherapy,
             anti-angiogenic drugs, or treatment under evaluation).

          4. At least one measurable site of disease as defined by RECIST 1.1 criteria.

          5. ECOG performance status of 0, 1.

          6. No toxicity > 1 according to the National Cancer Institute (NCI) Common Terminology
             Criteria for Adverse Events (CTCAE version 4.0)

          7. In case of prior radiation therapy, discontinuation of irradiation for at least 4
             weeks before first dose of study treatment. This period can be reduced to at least 1
             week in case of radiotherapy in a limited field (< 10% of the whole body) while no
             side effects grade ≥ 2 is expected and keeping at least one site for evaluation.

          8. Adequate bone marrow, liver and renal function, as defined below:

               -  Absolute neutrophil count ≥ 1.5 G/L, platelet count ≥ 100 G/L, and hemoglobin ≥ 9
                  g/dL),

               -  AST/ALT ≤ 3 x upper limit of normal (ULN) (or ≤ 5.0 x ULN if liver metastasis)
                  and total bilirubin ≤ 1.5 x ULN (≤ 2.5 x ULN if liver metastases),

               -  Serum creatinine ≤ 2.0 x ULN or creatinine clearance ≥ 50 mL/min according to
                  Cockroft formula or MDRD formula for patients older than 65 years,

          9. Absence of proteinuria confirmed by urinary dipstick test. If the dipstick test is ≥
             2+, proteinuria will be quantitated on a complete 24h urine sample (< 1 g/L of
             protein/24h sample).

         10. Adequate contraceptive methods for fertile female subjects for the whole duration of
             the study and for 7 days after the last dose of study drug.

             Note: Oral, implantable, or injectable contraceptives may be affected by cytochrome
             P450 interactions, and are not considered effective for this study.

         11. Covered by a medical insurance, in countries where applicable.

         12. Written informed consent before any study specific procedures or assessments.

        Exclusion Criteria:

        1- Prior TKI treatment in adjuvant situation for renal cancer.

        - Significant cardiovascular disease including:

          -  Disorder of left ventricular function with a LVEF < 50%,

          -  Uncontrolled arterial hypertension under adapted medication: systolic blood pressure ≥
             150 mmHg or diastolic blood pressure ≥ 100 mmHg or both despite appropriate therapy,
             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 within 6 months of screening.

             3- Presence of brain metastases on MRI or 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.

             4- Major surgical procedure, open biopsy, or serious none healing wound within 28 days
             prior to inclusion.

             5- Any active acute or chronic or uncontrolled infection/disorder that impair the
             ability to evaluate the patient or the ability for the patient to complete the study.

             6- Prior history of other malignancies other than PRCC (except for curatively treated
             basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the uterine
             cervix) unless the subjects has been free of the disease for at least 3 years.

             7- Inability to swallow oral medications, or presence of active inflammatory bowel
             disease, partial or complete bowel obstruction or chronic diarrhea.

             8- Patient included in another clinical trial, except for supportive care trials.

             9- Psychological, familial, sociological, or geographical conditions that would limit
             compliance with study protocol requirements.

             10- Pregnant or breastfeeding women (mandatory negative serum or urinary pregnancy
             test at study entry for all women of childbearing potential).