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

Inclusion criteria

• Primary tumour of the bladder or upper urinary tract
• Histologically confirmed infiltrating urothelial carcinoma (epidermoid and/or glandular forms are accepted)
• Patients without Harvey and Kirsten-rat sarcoma viral oncogene homolog mutations
• Advanced disease defined by a locally advanced stage (T4 and/or N+) ineligible for surgical resection, or a metastatic stage (M1)
• Patients with at least 1 evaluable lesion as per Response evaluation criteria in solid tumors version 1.1 (RECIST v1.1)
• 18 ≤ age ≤ 75 years
• General condition 0 or 1 as per the WHO scale
• 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)
• Haematological function: Haemoglobin >11 g/dl, neutrophils ≥1500/mm³, platelets ≥100,000/mm³
• Liver function: Grade* 0 Aspartate aminotransferase and Alanine aminotransferase (< grade* 3 for liver metastases), grade* 0 alkaline phosphatases, normal bilirubin
• Renal function: calculated (or measured) creatinine clearance >60 ml/min
• Patients covered by a social security scheme
• Patient having read the information sheet and signed the informed consent form.

Exclusion criteria

• Pure adenocarcinoma or pure epidermoid carcinoma or mixed or pure small-cell neuroendocrine carcinoma
• Previous treatment with one of the following molecules: methotrexate, vinblastine, doxorubicin or Epidermal Growth Factor inhibitor
• History of interstitial pneumonitis or pulmonary fibrosis
• 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)
• Ventricular ejection fraction <50%
• Blood calcium and/or magnesium ≥ grade* 1
• 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,
• Treatment with radiotherapy for analgesic purposes (unless treatment was discontinued at least 15 days prior to inclusion in the trial)
• Potential allergy to panitumumab
• 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
• Pregnant women, or female subjects liable to become pregnant or currently breast-feeding,
• Patient already included in another therapeutic trial on an investigational medicinal product,
• Persons deprived of their freedom or under judicial protection (including guardianship),
• Unable to receive medical follow-up during the trial owing to geographical, social or psychological reasons.