I-MVAC +/- Panitumumab as First-line Treatment of Advanced Urothelial Carcinoma Without H-Ras Nor K-Ras Mutations

Inclusion Criteria: 1. Primary tumour of the bladder or upper urinary tract 2. Histologically confirmed infiltrating urothelial carcinoma (epidermoid and/or glandular forms are accepted) 3. Patients without Harvey and Kirsten-rat sarcoma viral oncogene homolog mutations 4. Advanced disease defined by a locally advanced stage (T4 and/or N+) ineligible for surgical resection, or a metastatic stage (M1) 5. Patients with at least 1 evaluable lesion as per Response evaluation criteria in solid tumors version 1.1 (RECIST v1.1) 6. 18 ≤ age ≤ 75 years 7. General condition 0 or 1 as per the WHO scale 8. Absence of previous chemotherapy for advanced disease (chemotherapy with gemcitabine and platinum salt delivered as an adjuvant is accepted if this ended more than a year ago) 9. Haematological function: Haemoglobin \>11 g/dl, neutrophils ≥1500/mm³, platelets ≥100,000/mm³ 10. Liver function: Grade\* 0 Aspartate aminotransferase and Alanine aminotransferase (\< grade\* 3 for liver metastases), grade\* 0 alkaline phosphatases, normal bilirubin 11. Renal function: calculated (or measured) creatinine clearance \>60 ml/min 12. Patients covered by a social security scheme 13. Patient having read the information sheet and signed the informed consent form. Exclusion Criteria: 1. Pure adenocarcinoma or pure epidermoid carcinoma or mixed or pure small-cell neuroendocrine carcinoma 2. Previous treatment with one of the following molecules: methotrexate, vinblastine, doxorubicin or Epidermal Growth Factor inhibitor 3. History of interstitial pneumonitis or pulmonary fibrosis 4. History of cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, uncontrolled serious cardiac arrhythmia) in the year prior to randomisation (≤1 year) 5. Ventricular ejection fraction \<50% 6. Blood calcium and/or magnesium ≥ grade\* 1 7. History of cancer in the 5 years prior to entry in the trial other than basal cell skin cancer or in situ epithelioma of the cervix, 8. Treatment with radiotherapy for analgesic purposes (unless treatment was discontinued at least 15 days prior to inclusion in the trial) 9. Potential allergy to panitumumab 10. Male or female patients not agreeing to use an effective method of contraception throughout the duration of treatment and for 6 months after treatment discontinuation 11. Pregnant women, or female subjects liable to become pregnant or currently breast-feeding, 12. Patient already included in another therapeutic trial on an investigational medicinal product, 13. Persons deprived of their freedom or under judicial protection (including guardianship), 14. Unable to receive medical follow-up during the trial owing to geographical, social or psychological reasons.