Infiltrating Urothelial Carcinoma, KRAS Gene Mutation
Conditions
Brief summary
OBJECTIVES OF THE TRIAL Primary objective Evaluation of efficacy in terms of progression-free survival at 9 months of the combination of intensified methotrexate, vinblastine, doxorubicin and cisplatin with or without panitumumab as first-line treatment of advanced urothelial carcinoma in patients without Harvey nor Kirsten rat sarcoma viral oncogene homolog mutations. Secondary objectives * To assess toxicity * To assess response rate * To assess overall survival * To assess time to progression * To study the correlation between response rate, time to progression, overall survival and biological parameters
Interventions
DRUGChemotherapy
METHOTREXATE: 30 mg/m² on day 1 VINBLASTINE: 3 mg/m² on day 2 DOXORUBICIN: 30 mg/m² on day 2 CISPLATIN: 70 mg/m² on day 2
DRUGPanitumumab
PANITUMUMAB: 6 mg/kg on day 2
Sponsors
UNICANCER
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to progression | 9 months | Progression-Free Survival at 9 months post-treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicities assessment | 24 months | toxicity (CTC AE v4.0) after end of treatment |
| Evaluation of response | 24 months | Recist 1.1 |
| Evaluation of overall survival | 24 months | — |
| Evaluation of time to progression | 24 months | — |
Countries
France
Outcome results
None listed