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.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-011882-10-FR
• Date of registration: 04/01/2010
• Prospective Registration: Yes
• Primary sponsor: FNCLCC (Fédération Nationale des Centres de Lutte Contre le Cancer)
• Public title: 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.
• Scientific title: 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.
• Date of first enrolment: 26/02/2010
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-011882-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other: yes Other specify the comparator: I-MVAC therapy (reference arm)

Countries of recruitment

France

Key inclusion & exclusion criteria

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Advanced urothelial carcinoma in patients without H-Ras nor K-Ras mutations
MedDRA version: 12.1 Level: LLT Classification code 10046714 Term: Urothelial carcinoma bladder

Intervention(s)

Trade Name: LEDERTREXATE 1000 mg
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: METHOTREXATE
CAS Number: 59-05-2
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: not less then
Concentration number: 30-

Trade Name: VELBE 10 mg
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: VINBLASTINE
CAS Number: 865214
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: not less then
Concentration number: 3-

Trade Name: CISPLATINE DAKOTA PHARM
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: CISPLATIN
CAS Number: 15663271
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: not less then
Concentration number: 70-

Trade Name: DOXORUBICINE ACTAVIS
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: DOXORUBICIN
CAS Number: 23214-92-8
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: not less then
Concentration number: 30-

Trade Name: VECTIBIX
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PANITUMUMAB
CAS Number: 339177-26-3
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: not less then
Concentration number: 6-

Primary Outcome(s)

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.
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
scintigraphy.

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)
- To assess response rate (RR)
- To assess overall survival (OS)
- To assess time to progression (TTP)
- To study the correlation between response rate, time to progression, overall survival and biological
parameters.

Secondary ID(s)

GETUG-AFU 19/0901