Intensified methotrexate, vinblastine, doxorubicin and cisplatin (I-MVAC) with or without panitumumab as first-line treatment of advanced urothelial carcinoma in patients without H-Ras nor K-Ras mutations. Randomised phase II study.

• Conditions: Advanced urothelial carcinoma in patients without H-Ras nor K-Ras mutations; MedDRA version: 12.1Level: LLTClassification code 10046714Term: Urothelial carcinoma bladder

• Registration Number: EUCTR2009-011882-10-FR
• Lead Sponsor: FNCLCC (Fédération Nationale des Centres de Lutte Contre le Cancer)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-01-04
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

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 H-Ras nor K-Ras 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 RECIST criteria (version 1.1)
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 ASAT and ALAT (< 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.

* CTC AE v4.0
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 EGF-R 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.

* CTC AE v4.0

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluation of efficacy in terms of progression-free survival at 9 months of the combination of intensified methotrexate, vinblastine, doxorubicin and cisplatin (I-MVAC) with or without panitumumab as first-line treatment of advanced urothelial carcinoma in patients without H-Ras nor K-Ras mutations.;Secondary Objective: - To assess toxicity (CTC AE v4.0)<br>- To assess response rate (RR)<br>- To assess overall survival (OS)<br>- To assess time to progression (TTP)<br>- To study the correlation between response rate, time to progression, overall survival and biological<br>parameters.;Primary end point(s): The primary endpoint is the evaluation of efficacy, in terms of progression-free survival at 9 months, of the combination I-MVAC with or without panitumumab.<br>The criterion for progression will be evaluated as per RECIST criteria (version 1.1 in Appendix 6) for measurable lesions or by the development of at least 1 new lesions evidenced during bone<br>scintigraphy.